Harper's Illustrated Biochemistry-McGraw-Hill Medical (2003)

634 / CHAPTER 54 Genetic map
30 20 25 cM
20 30
Cytogenetic
map

Physical map
25 50 75 100 125 150 Mb

EcoRI Hind III NotI

Restriction map STS map

Contig map

Figure 54–1. Principal methods used to identify and isolate normal
and disease genes. For the genetic map, the positions of several hypo-
thetical genetic markers are shown, along with the genetic distances in
centimorgans between them. The circle shows the position of the cen-
tromere. For the cytogenetic map, the classic banding pattern of a hypo-
thetical chromosome is shown. For the physical map, the approximate
physical positions of the above genetic markers are shown, along with
the relative physical distances in megabase pairs. Examples of a restric-
tion map, a contig mark, and an STS map are also shown. (Reproduced,
with permission, from Green ED, Waterston RH: The Human Genome
Project: Prospects and implications for clinical medicine. JAMA 1991;266:
1966. Copyright © 1991 by the American Medical Association.)

Different Approaches Were Used (STSs), whose locations had been already determined.
STSs are short (usually < 500 bp), unique genomic loci
by the Two Groups for which a PCR assay is available. Clones of the BACs
were then broken into small fragments (shotgunning).
We shall summarize the major findings reported in the Each fragment was then sequenced, and computer algo-
two drafts and comment on their implications. While rithms were used that recognized matching sequence
there are differences between the drafts, they will not be information from overlapping fragments to piece to-
dwelt on here, as the areas of general agreement are gether the complete sequence.
much more extensive. It is worthwhile, however, to
summarize the different approaches used by the two Celera used the whole genome shotgun approach,
groups. Basically, the IHGSC employed a map first, in effect bypassing the mapping step. Shotgun frag-
sequence later approach. In part, this was because se- ments were assembled by algorithms onto large scaf-
quencing was a slow process when the public project folds, and the correct position of these scaffolds in the
started, and the strategy of the Consortium evolved genome was determined using STSs. A scaffold is a se-
over time as advances were made in sequencing and ries of “contigs” that are in the right order but not nec-
other techniques. The overall approach, referred to as essarily connected in one continuous sequence. Contigs
hierarchical shotgun sequencing, consisted of frag- are contiguous sequences of DNA made by assembling
menting the entire genome into pieces of approxi- overlapping sequenced fragments of a natural chromo-
mately 100–200 kb and inserting them into bacterial some or a BAC. The availability of high-throughput
artificial chromosomes (BACs). The BACs were then sequenators, powerful computer programs, the ele-
positioned on individual chromosomes by looking for ment of competition, and other factors accounted for the
marker sequences known as sequence-tagged sites rapid progress made by both groups from 1998 onward.

THE HUMAN GENOME PROJECT / 635

Table 54–1. Principal methods used to identify and isolate normal and disease genes.

Procedure Comments

Detection of specific cytogenetic For instance, a small deletion of band Xp21.2 was important in cloning the gene involved in

abnormalities Duchenne muscular dystrophy.

Extensive linkage studies Large families with defined pedigrees are desirable. Dominant genes are easier to recognize
than recessives.

Use of probes to define marker Probes identify STSs, RFLPs, SNPs,1 etc; thousands, covering all the chromosomes, are now
loci available. It is desirable to flank the gene on both sides, clearly delineating it.

Radiation hybrid mapping2 Now the most rapid method of localizing a gene or DNA fragment to a subregion of a human
chromosome and constructing a physical map.

Use of rodent or human somatic Permits assignment of a gene to one specific chromosome but not to a subregion.
cell hybrids

Fluorescence in situ hybridization Permits localization of a gene to one chromosomal band.

Use of pulsed-field gel Permits isolation of large DNA fragments obtained by use of restriction endonucleases (rare

electrophoresis (PFGE) to cutters) that result in very limited cutting of DNA.

separate large DNA fragments

Chromosome walking Involves repeated cloning of overlapping DNA segments; the procedure is laborious and can
usually cover only 100–200 kb.

Chromosome jumping By cutting DNA into relatively large fragments and circularizing it, one can move more quickly
and cover greater lengths of DNA than with chromosomal walking.

Cloning via YACs, BACs, cosmids, Permits isolation of fragments of varying lengths.
phages, and plasmids

Detection of expression of The mRNA should be expressed in affected tissues.
mRNAs in tissues by Northern
blotting using one or more
fragments of the gene as a
probe

PCR Can be used to amplify fragments of the gene; also many other applications.

DNA sequencing Establishes the highest resolution physical map. Identifies open reading frame. Facilities with
many high throughput instruments could sequence millions of base pairs per day.

Databases Comparison of DNA and protein sequences obtained from unknown gene with known se-
quences in databases can facilitate gene identification.

Abbreviations: STS, sequence tagged site; RFLP, restriction fragment linked polymorphism; SNP, single nucleotide polymorphism; YAC,
yeast artificial chromosome; BAC, bacterial artificial chromosome; PCR, polymerase chain reaction.
1Many single nucleotide polymorphisms (SNPs) are being detected and catalogued. These are stable and frequent, and their detection
can be automated. It is anticipated that they will be particularly useful for mapping complex traits such as diabetes mellitus.
2Radiation hybrid mapping (consult http://compgen.rutgers.edu/rhmap/ for a detailed bibliography of this technique) makes use of a
panel of somatic cell hybrids, with each cell line containing a random set of irradiated human genomic DNA in a hamster background.
Briefly, the radiation fragments the DNA into small pieces of variable length; if a gene is located close to another known gene, it is likely
that the two will remain linked (compare genetic linkage) on the same fragment. An STS marker is typed against a radiation hybrid panel
by using its two oligonucleotide primers to perform a PCR assay against the DNA from each hybrid cell line of the panel. If enough mark-
ers are typed on one panel, continuous linkage can be established along each arm of a chromosome, and the markers can be assembled
into the map as a single linkage group.

636 / CHAPTER 54 fly (13,061). The figures suggest that the complexity of
humans compared with that of the two simpler organ-
DETERMINATION OF THE SEQUENCE OF isms must have explanations other than strictly gene
THE HUMAN GENOME HAS PRODUCED A number.
WEALTH OF NEW FINDINGS
Only 1.1–1.5% of the Human
Only a small fraction of the findings can be covered Genome Encodes Proteins
here. The interested reader is referred to the original ar-
ticles. Table 54–2 summarizes a number of the high- Analyses of the available data reveal that 1.1–1.5% of
lights, which can now be described. the genome consists of exons. About 24% consists of
introns, and 75% of sequences lying between genes (in-
Most of the Human Genome tergenic). Comparisons with the data on the round-
Has Been Sequenced worm and fruit fly have shown that exon size across the
three species is relatively constant (mean size of 145 bp
Over 90% of the human genome had been sequenced in humans). However, intron size in humans is much
by July 2000. This is by far the largest genome se- more variable (mean size of over 3300 bp), resulting in
quenced, with an estimated size of approximately 3.2 great variation in gene size.
gigabases (Gb). Prior to the human genome, that of the
fruit fly had been the largest (~180 Mb) sequenced. The Landscape of Human Chromosomes
Gaps still exist, small and large, and the quality of some Varies Widely
of the sequencing data will be refined since some of the
findings are probably not exactly right. There are marked differences among individual chro-
mosomes in many features, such as gene number per
The Human Genome Is Estimated to megabase, density of single nucleotide polymorphisms
Encode About 30,000–40,000 Proteins (SNPs), GC content, number of transposable elements
and CpG islands, and recombination rate. To take one
The greatest surprise provided by the results to date has example, chromosome 19 has the richest gene content
been the apparently low number of genes encoding pro- (23 genes per megabase), whereas chromosome 13 and
teins, estimated to lie between 30,000 and 40,000. The the Y chromosome have the sparsest content (5 genes
higher number could increase as new data are obtained. per megabase). Explanations for these variations are not
This number is approximately twice that found in the apparent at this time.
roundworm (19,099) and three times that of the fruit
Human Genes Do More Work Than
Table 54–2. Major findings reported in the rough Those of Simpler Organisms
drafts of the human genome.
Alternative splicing appears to be more prevalent in hu-
• More than 90% of the genome has been sequenced; gaps, mans, involving at least 35% of their genes. Data indi-
large and small, remain to be filled in. cate that the average number of distinct transcripts per
gene for chromosomes 22 and 19 were 2.6 and 3.2, re-
• Estimated number of protein-coding genes ranges from spectively. These figures are higher than for the round-
30,000 to 40,000. worm, where only 12.2% of genes appear to be alterna-
tively spliced and only 1.34 splice variants per gene
• Only 1.1–1.5% of the genome codes for proteins. were noted.
• There are wide variations in features of individual chromo-
The Human Proteome Is More Complex
somes (eg, in gene number per Mb, SNP density, GC con- Than That of Invertebrates
tent, numbers of transposable elements and CpG islands,
recombination rate). Relatively few new protein domains appear to have
• Human genes do more work than those of the roundworm emerged among vertebrates. However, the number of
or fruit fly (eg, alternative splicing is used more frequently). distinct domain architectures (~1800) in human pro-
• The human proteome is more complex than that found in teins is 1.8 times that of the roundworm or fruit fly.
invertebrates. About 90 vertebrate-specific families of proteins have
• Repeat sequences probably constitute more than 50% of been identified, and these have been found to be en-
the genome. riched in proteins of the immune and nervous systems.
• Approximately 100 coding regions have been copied and
moved by RNA-based transposons.
• Approximately 200 genes may be derived from bacteria by
lateral transfer.
• More than 3 million SNPs have been identified.

The results of the two drafts are rich in information THE HUMAN GENOME PROJECT / 637
about protein families and classes. One example is
shown in Table 54–3, in which the major classes of Segmental duplications have been found to be much
proteins encoded by human genes are listed. As can be more common than in the roundworm or fruit fly. It is
seen, the largest class is “unknown.” Identification of possible that these structures may be involved in exon
these unknown proteins will be a major focus of activity shuffling and the increased diversity of proteins found
for many laboratories. in humans.

Repeat Sequences Probably Constitute Other Findings of Interest
More Than 50% of the Human Genome
The last three major points of interest listed in Table
Repeat sequences probably account for at least half of 54–2 will be briefly described together.
the genome. They fall into five classes: (1) transposon-
derived repeats (interspersed repeats); (2) processed Approximately 100 coding regions are estimated to
pseudogenes; (3) simple sequence repeats; (4) segmental have been copied and moved by RNA-based trans-
duplications, made up of 10–300 kb that have been posons (retrotransposons). It is possible that some of
copied from one region of the genome into another; these genes may adopt new roles in the course of time.
and (5) blocks of tandemly repeated sequences, found A surprising finding is that over 200 genes may be de-
at centromeres, telomeres, and other areas. Consider- rived from bacteria by lateral transfer. None of these
able information on most of the above classes of repeat genes are present in nonvertebrate eukaryotes. More
sequences—of great value in understanding the archi- than 3 million SNPs have been identified. It is likely
tecture and development of the human genome—is re- that they will prove invaluable for certain aspects of
ported in the drafts. Only two points of interest will be gene mapping.
mentioned here. It is speculated that Alu elements, the
most prominent members (about 10% of the total It is stressed that the findings listed here are only a
genome) of the short interspersed elements (SINEs), few of those reported in the drafts, and the reader is
may be present in GC-rich areas because of positive se- urged to consult the original reports (see References,
lection, implying that they are of benefit to the host. below).

Table 54–3. Major classes of proteins encoded by FURTHER WORK IS PLANNED ON THE
human genes.1 HUMAN & OTHER GENOMES

Class of Protein Number (%)2 The IHGSC has indicated that it will determine the
complete sequence, it is hoped, by 2003. The task in-
Unknown 12,809 (41%) volves filling in the gaps and identifying new genes,
their locations, and functions. Regulatory regions will
Nucleic acid enzymes 2,308 (7.5%) be identified, and the sequences of other large genomes
(eg, of the house mouse; of Rattus norvegicus, the Nor-
Transcription factors 1,850 (6%) way rat; of Danio rerio, the zebra fish; of Fugu rubripes,
the tiger puffer fish; and of one or more primates) will
Receptors 1,543 (5%) be obtained; indeed, a draft version of the genome of
the tiger puffer fish was published in 2002. Additional
Hydrolases 1,227 (4.0%) SNPs will be identified; a complete catalog of these
variants is expected to be of great value in mapping
Select regulatory molecules (eg, 988 (3.2%) genes associated with complex traits and for other uses
G proteins, cell cycle regulators) as well. Along with the above, existing databases will be
added to as new information flows in, and new data-
Protooncogenes 902 (2.9%) bases will probably be established to serve specific pur-
poses. A variety of studies in functional genomics (ie,
Cytoskeletal structural proteins 876 (2.8%) the study of genomes to determine the functions of all
their genes and their products) will also be undertaken.
Kinases 868 (2.8%)
IMPLICATIONS FOR PROTEOMICS,
1Data from Venter JC et al: The sequence of the human genome. BIOTECHNOLOGY, & BIOINFORMATICS
Science 2001;291:1304.
2The percentages are derived from a total of 26,383 genes re- Many fields will be influenced by knowledge of the
ported in the rough draft by Celera Genomics. Classes containing human genome. Only a few are briefly discussed here.
more than 2.5% of the total proteins encoded by the genes iden-
tified when this rough draft was written are arbitrarily listed as Proteomics (see Chapter 4) in its broadest sense is
major. the study of all the proteins encoded in an organism (ie,

638 / CHAPTER 54 effects on health services and the diagnosis and treat-
ment of disease.
the proteome), including their structures, modifica-
tions, functions, and interactions. In a narrower sense, SUMMARY
it involves the identification and study of multiple pro-
teins linked through cellular actions—but not necessar- • Determination of the complete sequence of the
ily the entire proteome. With regard to humans, many human genome, now almost completed, is one of the
individual proteins will be identified and characterized; most significant scientific achievements of all time.
their interactions and levels will be determined in phys-
iologic and pathologic states, and the resulting informa- • Many important findings have already emerged. The
tion will be entered into appropriate databases. Tech- one to date that has generated the most discussion is
niques such as two-dimensional electrophoresis, a that the number of human genes may be only two to
variety of modes of mass spectrometry, and antibody three times that estimated for the roundworm and
arrays will be central to expansion of this rapidly grow- the fruit fly.
ing field. Overall, proteomics will greatly advance our
knowledge of proteins at the basic level and will also • Information flowing from the Human Genome Proj-
nourish biotechnology as new proteins that are likely ect is having major influences in fields such as pro-
to have diagnostic, therapeutic, and other uses are dis- teomics, bioinformatics, biotechnology, and phar-
covered and methods for their economic production are macogenomics as well as all areas of biology and
developed. Specialists in bioinformatics will be in de- medicine.
mand, as this field rapidly gears up to manage, analyze,
and utilize the flood of data from genomic and pro- • It is hoped that the knowledge derived will be used
teomic studies. wisely and fairly and that the benefits that will ensue
regarding health, disease, and other matters will be
IMPLICATIONS FOR MEDICINE made available to all people everywhere.

Practically every area of medicine will be affected by the REFERENCES
new information accruing from knowledge of the
human genome. The tracking of disease genes will be Collins FS, McKusick VA: Implications of the Human Genome
enormously facilitated. As mentioned above, SNP maps Project for medical science. JAMA 2001;285:540. (The Feb-
should greatly assist determination of genes involved in ruary 7, 2001, issue describes opportunities for medical re-
complex diseases. Probes for any gene will be available search in the 21st century. Many articles of interest.)
if needed, leading to improved diagnostic testing for
disease susceptibility genes and for genes directly in- Hedges SB, Kumar S: Vertebrate genomes compared. Science
volved in the causation of specific diseases. The field of 2002;297:1283. (The same issue—No. 5585, August 23—
pharmacogenomics (see Chapter 53) is already ex- contains a draft version of the genome of the tiger puffer
panding greatly, and it is possible that in the future fish.)
drugs will be tailored to accommodate the variations in
enzymes and other proteins involved in drug action and McKusick VA: The anatomy of the human genome: a neo-Vesalian
metabolism found among individuals. Studies of genes basis for medicine in the 21st century. JAMA 2001;286:
involved in behavior may lead to new insights into the 2289. (The November 14, 2001, issue contains a number of
causation and possible treatment of psychiatric disor- other excellent articles—eg, on clinical proteomics, pharma-
ders. Many ethical issues—eg, privacy concerns and cogenomics—relating to the Human Genome Project and its
the use of genomic information for commercial pur- impact on medicine.)
poses—will have to be addressed. It will also be impor-
tant that medical and economic benefits accrue to indi- Nature 2001;409(6822) (February 15), and Science 2001;291
viduals in Third World countries from the anticipated (5507) (February 16). (These two issues present the rough
drafts prepared by the IHGSC and Celera, respectively, along
with many other articles analyzing the meaning and signifi-
cance of the findings.)

Science 2001;294(5540) (October 5). (This issue contains a num-
ber of articles under the title Genome: Unlocking Biology’s
Storehouse. They describe new ideas, approaches, and re-
search related to genome information.)

APPENDIX

SELECTED WORLD WIDE WEB SITES (Maintains the EMBL Nucleotide and SWISS-PROT databases as
well as other databases.)
The following is a list of Web sites that readers may
find useful. The sites have been visited at various times GeneCards: http://bioinformatics.weizmann.ac.il/cards/
by one of the authors (RKM). Most are located in the
USA, but many provide extensive links to international (A database of human genes, their products, and their involvements
sites and to databases (eg, for protein and nucleic acid in diseases. From the Weizmann Institute of Science.)
sequences) and online journals. RKM would be grateful
if readers who find other useful sites would notify him GeneTestsGeneClinics: http://www.geneclinics.org/
of their URLs by e-mail (rmurray6745@rogers. com) so
that they may be considered for inclusion in future edi- (A medical genetics information resource with comprehensive arti-
tions of this text. cles on many genetic diseases.)

Readers should note that URLs may change or cease Genes and Disease: http://www.ncbi.nlm.nih.gov/disease/
to exist.
(Coverage of the genetic basis of many different types of diseases.)
ACCESS TO THE BIOMEDICAL
LITERATURE The Glycoscience Network (TGN): http://www.vei.co.uk/TGN/
tgn_side.htm
HighWire Press: http://highwire.stanford.edu
(Extensive lists of various classes of journals—biology, medicine, (TGN is an informal worldwide grouping of scientists who share an
interest in carbohydrates. The site contains considerable in-
etc—and offers also the most extensive list of journals with formation on carbohydrates and an extensive list of links to
free online access.) other sites dealing with sugar-containing molecules).
National Library of Medicine: http://www.nlm.nih.gov/
(Free access to Medline via PubMed.) Howard Hughes Medical Institute: http://www.hhmi.org/

GENERAL RESOURCE SITES (An excellent site for following current biomedical research. Con-
tains a comprehensive Research News Archive.)
The Biology Project (from the University of Arizona): http://
www.biology.arizona.edu/default.html The Human Gene Mutation Database: http://archive.uwcm.ac.uk/
uwcm/mg/hgmd0.html
Harvard Department of Molecular & Cellular Biology Links:
http://mcb.harvard.edu/BioLinks.html (An extensive tabulation of mutations in human genes from the In-
stitute of Medical Genetics in Cardiff, Wales.)
SITES ON SPECIFIC TOPICS
Human Genome Project Information: http://www.ornl.gov/hgmis/
American Heart Association: http://www.americanheart.org
(Useful information on nutrition, on the role of various biomole- (From the Human Genome Program of the United States Depart-
ment of Energy.)
cules—eg, cholesterol, lipoproteins—in heart disease, and on
the major cardiovascular diseases.) The Institute for Genetic Research: http://www.tigr.org/
Cancer Genome Anatomy Project (CGAP): http://www.ncbi.nlm.
nih.gov/ncicgap (Sequences of various bacterial genomes and other information.)
(An interdisciplinary program to generate the information and
technical tools needed to decipher the molecular anatomy of Karolinska Institute Nutritional and Metabolic Diseases: http://
the cancer cell.) www.mic.ki.se/Diseases/c18.html
European Bioinformatics Institute: http://www.ebi.ac.uk/ebi_
home.html (Access to information on many nutritional and metabolic disor-
ders.)

MITOMAP: http://www.mitomap.org/

(A human mitochondrial genome database.)

National Center for Biotechnology Information: http://ncbi.nlm.
nih.gov/

(Information on molecular biology and how molecular processes af-
fect human health and disease.)

National Human Genome Research Institute: http://www.genome.
gov/

(Extensive information about the Human Genome Project.)

National Institutes of Health (NIH): http://www.nih.gov/

(Includes links to the separate Institutes and Centers that constitute
NIH, covering a wide range of biomedical research.)

Neuroscience (Biosciences): http://neuro.med.cornell.edu/VL/

(A comprehensive list of neuroscience resources; part of the World-
Wide Web Virtual Library.)

639

640 / APPENDIX http://www.mc.vanderbilt.edu/peds/pidl/genetic/ehlers.htm

Office of Rare Diseases: http://rarediseases.info.nih.gov/index_ Chapter 6
main.html
http://sickle.bwh.harvard.edu/
(Access to information on more than 7000 rare diseases, including http://globin.cse.psu.edu/
current research.)
Chapter 7
OMIM Home Page—Online Mendelian Inheritance in Man:
http://www.ncbi.nlm.nih.gov/omim/ http://s02.middlebury.edu/CH441A/EnzymeTutorials.html
http://www.i-a-s.de/IAS/botanik/e18/18.htm
(An extensive catalog of human genetic disorders, updated daily.
Lists access to various allied resources.) Chapter 8

Protein Data Bank (PDB): http://www.rcsb.org/pdb/ http://www.indstate.edu/thcme/mwking/enzyme-kinetics.html
(A worldwide repository for the processing and distribution of http://ntri.tamuk.edu/cell/kinetics.html

three-dimensional biologic macromolecular structure data.) Chapter 9
The Protein Kinase Resource: http://pkr.sdsc.edu/html/index.
http://users.wmin.ac.uk/~mellerj/physiology/bernard.htm
shtml http://www.cm.utexas.edu/academic/courses/Fall2001/CH369/
(Information on the protein kinase family of enzymes.)
The Protein Society: http://www.faseb.org/protein/index.html LEC06/Lec6.htm
(An extensive list of Web resources for protein scientists.) http://www.cellularsignaling.org
Signaling Update: http://www.signaling-update.org/ http://arethusa.unh.edu/bchm752/ppthtml/Jan27/sld015.htm
(A one-stop overview for the specialist or nonspecialist of what is
Chapter 22
happening in cell signaling.)
Society for Endocrinology: http://www.endocrinology.org http://www.auhs.edu/netbiochem/NetWelco.htm
(Aims to promote advancement of public education in endocrinol-
Chapter 28
ogy. Contains a number of articles on endocrinology and a
list of links to other relevant sites.) http://www.people.virginia.edu/~rjh9u/scurvy.html
tbase—the Transgenic/Targeted Mutation Database at the Jackson http://www.mc.vanderbilt.edu/biolib/hc/journeys/scurvy.html
Laboratory, Bar Harbor, Maine: http://tbase.jax.org/ http://opbs.okstate.edu/~melcher/MG/MGW2/MG2411.html
(An attempt to organize information on transgenic animals and tar-
geted mutations generated and analyzed worldwide.) Chapter 29
The Wellcome Trust Sanger Institute: http://www.sanger.ac.uk
(A genome research center whose purpose it is to increase knowl- http://www.nucdf.org/whatis.htm
edge of genomes, particularly through large-scale sequencing
and analysis,) Chapter 30
Whitehead Institute/MIT Center for Genome Research: http://
www.genome.wi.mit.edu/ http://www.pkunetwork.org/
(Access to various databases and articles entitled “What’s New in http://www.rarediseases.org/search/rdblist.html
Genome Research.”) http://www.msud-support.org/overv.htm

Chapter 2 Chapter 34

http://www.geocities.com/bioelectrochemistry/sorensen.htm http://www.rarediseases.org/search/rdblist.html
http://www.rheumatology.org/patients/factsheet/gout.html
Chapter 3 http://www.merck.com/pubs/mmanual/section5/chapter55/55a.htm
http://www.nlm.nih.gov/medlineplus/goutandpseudogout.html
http: //www.bio.cmu.edu/Courses/03231 http://www.amg.gda.pl/~essppmm/ppd/ppd_py_umps.html
http: //www.bcbp.gu.se/~orjan/bmstruct/

Chapter 4

http://www.lundberg.bcbp.gu.se/~orjan/bmstruct/

Chapter 5

http://www.umass.edu/microbio/chime/explorer/
http://molvis.sdsc.edu/protexpl/index.htm
http://www.umass.edu/microbio/rasmol/
http://www.cryst.bbk.ac.uk/PPS2/course/section10/membrane.html
http://molbio.info.nih.gov/cgi-bin/pdb/

BIOCHEMICAL JOURNALS AND REVIEWS APPENDIX / 641

The following is a partial list of biochemistry journals Biochimica et Biophysica Acta (Biochim Biophys
and review series and of some biomedical journals that Acta)
contain biochemical articles. Biochemistry and biology Biochimie (Biochimie)
journals now usually have Web sites, often with useful European Journal of Biochemistry (Eur J Biochem)
links, and some journals are fully accessible without Indian Journal of Biochemistry and Biophysics (In-
charge. The reader can obtain the URLs for the follow- dian J Biochem Biophys)
ing by using a search engine. Journal of Biochemistry (Tokyo) (J Biochem
[Tokyo])
Annual Reviews of Biochemistry, Cell and Develop- Journal of Biological Chemistry (J Biol Chem)
mental Biology, Genetics, Genomics and Human Journal of Clinical Investigation (J Clin Invest)
Genetics Journal of Lipid Research (J Lipid Res)
Archives of Biochemistry and Biophysics (Arch Nature (Nature)
Biochem Biophys) Nature Genetics (Nat Genet)
Biochemical and Biophysical Research Communica- Proceedings of the National Academy of Sciences
tions (Biochem Biophys Res Commun) USA (Proc Natl Acad Sci USA)
Biochemical Journal (Biochem J) Science (Science)
Biochemistry (Biochemistry) Trends in Biochemical Sciences (Trends Biochem
Biochemistry (Moscow) (Biochemistry [Mosc]) Sci)

Index

Note: Page numbers in bold face type indicate a major discussion. A t following a page number indicates tabular ma-
terial and an f following a page number indicates a figure.

A bands, 556, 557f, 558f formation of, 254f, 255–259, 255f, 256f, molecular structure affecting strength of,
A blood group substance, 618, 619f 257f, 258f, 259f 12, 12t
A cyclins, 333, 334f, 335t
A gene, GalNAc transferase encoded by, lipogenesis and, 173–177, 174f, 175f polyfunctional, nucleotides as, 290
as fatty acid building block, 176–177 as proton donors, 9
618–619 strong, 9
A (aminoacyl/acceptor) site, aminoacyl- pyruvate dehydrogenase regulated by, weak. See Weak acids
141–142, 142f, 178 Aciduria
tRNA binding to, in protein dicarboxylic, 188
synthesis, 368, 368f pyruvate oxidation to, 134, 135f, methylmalonic, 155
ABC-1. See ATP-binding cassette 140–142, 141f, 142f, 143t orotic, 300, 301
transporter-1 urocanic, 250
Abetalipoproteinemia, 207, 228t xenobiotic metabolism and, 630 Aconitase (aconitate hydratase), 130
ABO blood group system, biochemical basis Acetyl-CoA carboxylase, 156t, 179 ACP. See Acyl carrier protein
of, 617–619, 619f Acrosomal reaction, glycoproteins in, 528
Absorption, 474–480 in lipogenesis regulation, 156t, 173, ACTH. See Adrenocorticotropic hormone
Absorption chromatography, for 174f, 178, 178f, 179 Actin, 557, 559, 560
protein/peptide purification, 22 decoration of, 561, 561f
Absorption spectra, of porphyrins, N-Acetylgalactosamine (GalNAc), in fibronectin receptor interacting with,
273–274, 277f glycoproteins, 515, 516t
Absorptive pinocytosis, 430 540, 541f
ACAT (acyl-CoA:cholesterol acyltrans- N-Acetylglucosamine (GlcNAc), in in muscle contraction, 557–559, 558f,
ferase), 223 glycoproteins, 516t
Accelerator (Ac-) globulin (factor V), 600t, 561–562, 561f, 562f
601, 602f N-Acetylglucosamine phosphotransferase regulation of striated muscle and,
Acceptor (A/aminoacyl) site, aminoacyl- (GlcNAc phosphotransferase)
tRNA binding to, in protein 562–563
synthesis, 368, 368f in I-cell disease, 532 in nonmuscle cells, 576–577
Acceptor arm, of tRNA, 310, 312f, 360, in pseudo-Hurler polydystrophy, 532 in red cell membranes, 615f, 616f, 616t,
361f N-Acetylglutamate, in urea biosynthesis,
Aceruloplasminemia, 589 617
ACEs. See Angiotensin-converting enzyme 245, 246f in striated vs. smooth muscle, 572t
inhibitors Acetyl hexosamines, in glycoproteins, 109t β-Actin, 577
Acetal links, 105–106 N-Acetyl lactosamines, on N-linked glycan F-Actin, 559, 559f, 561
Acetic acid, 112t in nonmuscle cells, 576, 577
pK/pKa value of, 12t chains, 521 G-Actin, 559, 559f
Acetoacetate, 183–184, 184f Acetyl (acyl)-malonyl enzyme, 173, 175f in nonmuscle cells, 576
in tyrosine catabolism, 254f, 255 N-Acetyl neuraminic acid, 169, 171f γ-Actin, 577
Acetoacetyl-CoA synthetase, in mevalonate Actin-filament capping protein, 540, 541f
synthesis, 219, 220f in gangliosides, 201, 203f Actin (thin) filaments, 557, 558f, 559f
Acetone, 183 in glycoproteins, 169, 171f, 515, 516t α-Actinin, 540, 566t
Acetone bodies. See Ketone bodies in mucins, 519f, 520 Activated protein C, in blood coagulation,
Acetylation Acetyl transacylase, 173, 174f, 175f
in covalent modification, mass increases Acetyltransferases, xenobiotic metabolism 603
and, 27t Activation energy, 61, 63
of xenobiotics, 630 and, 630 Activation energy barrier, enzymes affecting,
Acetyl-CoA, 122, 122f Acholuric jaundice, 282
carbohydrate metabolism and, 122, 122f, Achondroplasia, 432t, 551t, 553–554, 554f 63
123f Acid anhydride bonds, 287 Activation function 1, 460
catabolism of, 130–135, 131f, 132f. See Acid anhydrides, group transfer potential Activation function 2, 460
also Citric acid cycle Activation reaction, 456, 458f
cholesterol synthesis and, 219–220, 220f, for, 289–290, 289f, 290f, 290t Activator-recruited cofactor (ARC), 472t,
221f, 222f Acid-base balance, ammonia metabolism in,
fatty acid oxidation to, 123–124, 123f, 473
181–183, 181f, 182f 245 Activators
Acid-base catalysis, 51–52
in regulation of gene expression, 374,
HIV protease in, 52, 53f 376. See also Enhancers
α1-Acid glycoprotein (orosomucoid), 583t
Acid hydrolysis, for polypeptide cleavage, transcription, 351, 351t
Active chromatin, 316–318, 318f, 383
26t Active site, 51, 51f. See also Catalytic site
Acid phosphatase, diagnostic significance
∆GF and, 63
of, 57t
Acidemia, isovaleric, 259, 259–262
Acidosis

lactic. See Lactic acidosis
metabolic, ammonia in, 245
Acids
conjugate, 10

643

644 / INDEX metabolism in, 214–215, 214f, 235t Alanine (alanine-pyruvate) aminotransferase
control of, 216–217 (ALT/SGPT)
Active sulfate (adenosine 3′-phosphate-
5′-phosphosulfate), 289, 289f, 629 ADP, 287f diagnostic significance of, 57t
free energy of hydrolysis of, 82t in urea synthesis, 243–244, 244f
Active transport, 423, 423t, 424f, 426–427, mitochondrial respiratory rate and, β-Alanyl dipeptides, 264, 265f
427–428, 428f 94–95, 97t, 98f Albumin, 580, 581f, 583–584, 583t
myosin, muscle contraction and, 561, conjugated bilirubin binding to, 283
in bilirubin secretion, 280, 281f 561f free fatty acids in combination with, 180,
Activity (physical), energy expenditure and, in platelet activation, 606f, 607
in respiratory control, 94–95, 97, 97t, 206, 206t, 584
478 98f, 134–135 glomerular membrane permeability to,
Actomyosin, 560 structure of, 83f
ACTR coactivator, 472, 472t 540–541
Acute fatty liver of pregnancy, 188 ADP/ATP transporter, 95, 98f Albuminuria, 542
Acute inflammatory response, neutrophils ADPase, 607, 607t Alcohol, ethyl. See Ethanol
ADP-chaperone complex, 508. See also Alcohol dehydrogenase, in fatty liver, 212
in, 620 Alcoholism
Acute phase proteins, 583, 583t Chaperones
ADP-ribose, NAD as source of, 490 cirrhosis and, 212
negative, vitamin A as, 483–484 ADP-ribosylation, 490 fatty liver and, 212–214
Acylcarnitine, 180–181, 181f Adrenal cortical hormones. See also specific Aldehyde dehydrogenase, 87
Acyl carrier protein (ACP), 173, 174f in fatty liver, 212
hormone and Glucocorticoids; Aldolase A, deficiency of, 143
synthesis of, from pantothenic acid, 173, Mineralocorticoids Aldolase B, 167, 168f
495 synthesis of, 438–442, 440f, 441f deficiency of, 171
Adrenal gland, cytochrome P450 isoforms Aldolases, in glycolysis, 137, 138f
Acyl-CoA:cholesterol acyltransferase in, 627 Aldose-ketose isomerism, 103f, 104, 104f
(ACAT), 223 Adrenal medulla, catecholamines produced Aldose reductase, 167, 169f, 172
in, 445 Aldoses, 102, 102t, 104t
Acyl-CoA dehydrogenase, 87, 181, 182f Adrenergic receptors, in glycogenolysis, 148 ring structure of, 104
medium-chain, deficiency of, 188 Adrenocorticotropic hormone (ACTH), Aldosterone
437, 438, 439f, 453, 453f binding of, 455
Acyl-CoA synthetase (thiokinase) Adrenodoxin, 627 synthesis of, 438–440, 441f
in fatty acid activation, 180, 181f Adrenodoxin reductase, 627
in triacylglycerol synthesis, 199, 214f, 215 Adrenogenital syndrome, 442 angiotensin affecting, 451, 452
Adrenoleukodystrophy, neonatal, 503, 503t Aldosterone synthase (18-hydroxylase), in
Acylglycerols, 197 Aerobic glycolysis, 139
metabolism of, 197–201 as muscle ATP source, 575, 575f, 575t steroid synthesis, 440, 441f
catabolism, 197 Aerobic respiration Alkaline phosphatase
clinical aspects of, 202 citric acid cycle and, 130
synthesis, 197–201, 197f, 198f AF-1. See Activation function 1 in bone mineralization, 550
in endoplasmic reticulum, 126, 127f AF-2. See Activation function 2 isozymes of, diagnostic significance of,
AF-2 domain, 470
Adapter proteins, in absorptive pinocytosis, Affinity chromatography 57t
430 for protein/peptide purification, 23 in recombinant DNA technology, 400t
in recombinant fusion protein Alkalosis, metabolic, ammonia in, 245
Adenine, 288f, 288t purification, 58, 59f Alkaptonuria, 255
Adenosine, 287f, 288t AFP. See Alpha-fetoprotein Allergic reactions, peptide absorption
Agammaglobulinemia, 595
base pairing of in DNA, 303, 304, 305f Age, xenobiotic-metabolizing enzymes causing, 474
in uric acid formation, 299, 299f affected by, 630 Allopurinol, 290, 297
Adenosine deaminase Aggrecan, 542, 551t, 553, 553f Allosteric activators, 157
deficiency of, 300 Aggregates, formation of after denaturation, Allosteric effectors/modifiers, 129
localization of gene for, 407t 36
Adenosine diphosphate. See ADP Aging, glycosaminoglycans and, 549 in gluconeogenesis regulation, 157
Adenosine monophosphate. See AMP Aglycone, 105, 106 negative, 74. See also Feedback inhibition
Adenosine 3′-phosphate-5′-phosphosulfate, AHG. See Antihemophilic factor A/globulin second messengers as, 76
AIB1 coactivator, 472, 472t Allosteric enzymes, 75, 129
289, 289f, 629 ALA. See Aminolevulinate aspartate transcarbamoylase as model of,
Adenosine triphosphate. See ATP Alanine, 15t
S-Adenosylmethionine, 258f, 259, 264, pI of, 17 75
in pyruvate formation, 250, 252f Allosteric properties of hemoglobin, 42–46
266f, 289, 290f, 290t synthesis of, 237, 238f Allosteric regulation, of enzymatic catalysis,
Adenylic acid, as second messenger, 457 β-Alanine, 264, 300, 301f
Adenylyl cyclase 74, 74–76, 75f, 128f, 129
gluconeogenesis regulation and, 157
in cAMP-dependent signal transduction, Allosteric site, 74, 75
458–459, 460t Alpha-adrenergic receptors, in

cAMP derived from, 147 glycogenolysis, 148
in lipolysis, 215, 216f Alpha-amino acids. See also Amino acids
Adenylyl kinase (myokinase), 84
deficiencies of, 151–152 genetic code specifying, 14, 15–16t
in gluconeogenesis regulation, 157 in proteins, 14
as source of ATP in muscle, 573, 575f
Adhesion molecules, 529, 529t. See also Cell

adhesion
Adipose tissue, 111, 214–215, 214f

brown, 217, 217f

Alpha-amino nitrogen. See Amino acid absorption of, 477 INDEX / 645
nitrogen analysis/identification of, 20
blood glucose and, 159 Aminolevulinate dehydratase, 270, 273f
Alpha anomers, 104 branched chain, catabolism of, 259, in porphyria, 274, 277t
Alpha1 antiproteinase/antitrypsin. See
260f, 261f, 262f Aminolevulinate synthase, 270, 272–273,
α1-Antiproteinase disorders of, 259–262 273f, 276f
Alpha- (α) carotene, 482 in catalysis, conservation of, 54, 55t
Alpha-fetoprotein, 583t chemical reactions of, functional groups in porphyria, 274, 277f, 278
Alpha-globin gene, localization of, 407t Aminopeptidases, 477
Alpha (α) helix, 31–32, 32f, 33f dictating, 18–20 Aminophospholipids, membrane
deamination of. See Deamination
amphipathic, 31–32 deficiency of, 237, 480 asymmetry and, 420
in myoglobin, 40, 41f excitatory. See also Aspartate; Glutamate Aminoproteinase, procollagen, 537
Alpha (α) ketoglutarate. See glucogenic, 231–232 Amino sugars (hexosamines), 106, 106f
in gluconeogenesis, 133–134, 134f
α-Ketoglutarate interconvertability of, 231–232 glucose as precursor of, 169, 171f
Alpha-lipoproteins, 205. See also High- keto acid replacement of in diet, 240 in glycosaminoglycans, 109, 169, 171f
ketogenic, 232 in glycosphingolipids, 169, 171f
density lipoproteins melting point of, 18 interrelationships in metabolism of,
familial deficiency of, 228t metabolism of, 122f, 124, 124f, 125f. See
Alpha-R groups, amino acid properties 171f
also Amino acid carbon skeletons, Aminotransferases (transaminases),
affected by, 18 catabolism of; Amino acid
Alpha (α) thalassemia, 47 nitrogen, catabolism of 133–134, 134f
Alpha-tocopherol. See Tocopherol pyridoxal phosphate in, 491 diagnostic significance of, 57t
Alport syndrome, 538, 538t net charge of, 16–17, 17f in urea biosynthesis, 243–244, 244f
ALT. See Alanine aminotransferase nutritionally essential, 124 Ammonia
Alteplase (tissue plasminogen activator/t-PA), nutritionally nonessential, 124 in acid-base balance, 245
synthesis of, 237–241 detoxification of, 242
604–605, 605f, 606t, 607t in peptides, 14, 19, 19f excess of, 247
Alternative pathway, of complement pK/pKa values of, 15–16t, 17, 17f glutamine synthase fixing, 245, 245f
environment affecting, 18, 18t nitrogen removed as, 244, 244f
activation, 596 products derived from, 264–269. See also Ammonia intoxication, 244
Altitude, high, adaptation to, 46 specific product Ammonium ion, pK/pKa value of, 12t
Alu family, 321–322 properties of, 14–18 Amobarbital, oxidative phosphorylation/
Alzheimer disease, amyloid in, 37, 590 α-R group determining, 18
α-Amanitin, RNA polymerases affected by, protein degradation and, 242, 243f respiratory chain affected by, 92,
in proteins, 14 95, 96f
343 removal of ammonia from, 244, 244f AMP, 287f, 288f, 288t, 297f
Ambiguity, genetic code and, 359 requirements for, 480 coenzyme derivatives of, 290t
Amino acid carbon skeletons, catabolism of, sequence of, primary structure cyclic. See Cyclic AMP
determined by, 18–19 free energy of hydrolysis of, 82t
249–263 solubility point of, 18 IMP conversion to, 293, 296f
acetyl-CoA formation and, 254f, substitutions of, missense mutations feedback-regulation of, 294, 296f
caused by, 362–363, 362f PRPP glutamyl amidotransferase
255–259, 255f, 256f, 257f, 258f, synthesis of, 237–241 regulated by, 294
259f in carbohydrate metabolism, 123 structure of, 83f, 288f
branched-chain, 259, 260f, 261f, 262f citric acid cycle in, 133, 134f Amp resistance genes, 402, 403f
disorders of, 259–262 transamination of. See Transamination Amphibolic pathways/processes, 122
pyruvate formation and, 250–255, 252f, transporter/carrier systems for, 99 citric acid cycle and, 133
253f glutathione and, 629–630 Amphipathic α-helix, 31–32
transamination in initiation of, 249–250, hormones affecting, 427 Amphipathic lipids, 119–121, 120f
249f, 250f, 251f Aminoacyl residues, 18–19 in lipoproteins, 205, 207f
Amino acid nitrogen peptide structure and, 19 in membranes, 119, 120f, 417–418, 417f
catabolism of, 242–248 Aminoacyl (A/acceptor) site, aminoacyl- Amphipathic molecules, folding and, 6
in amino acid carbon skeleton tRNA binding to, in protein Ampicillin resistance genes, 402, 403f
catabolism, 249, 249f synthesis, 368, 368f Amplification, gene, in gene expression
end products of, 242–243 Aminoacyl-tRNA, in protein synthesis, 368 regulation, 392–393, 393f
urea as, 245–247, 246f Aminoacyl-tRNA synthetases, 360, 360f Amylases
L-glutamate dehydrogenase in, γ-Aminobutyrate, 267, 268f diagnostic significance of, 57t
244–245, 244f, 245f β-Aminoisobutyrate, 300, 301f in hydrolysis of starch, 474
transamination of, 243–244, 243f Aminolevulinate (ALA), 270, 273f β-Amyloid, in Alzheimer disease, 37, 590
L-Amino acid oxidase, 86–87 in porphyria, 278 Amyloid-associated protein, 590
in nitrogen metabolism, 244, 244f Amyloid precursor proteins, 590
Amino acid sequences. See also Protein in Alzheimer disease, 37, 590
sequencing Amyloidosis, 590–591
determination of, for glycoproteins, 515t Amylopectin, 107, 108f
primary structure determined by, 18–19 Amylopectinosis, 152t
repeating, in mucins, 519, 520f Amylose, 107, 108f
Amino acids, 2, 14–20, 15–16t. See also
Peptides

646 / INDEX Anti conformers, 287, 287f Apo A-IV, 206, 206t
Antibiotics Apo B-48, 206, 206t
Anabolic pathways/anabolism, 81, 122. See Apo B-100, 206, 206t
also Endergonic reaction; amino sugars in, 106
Metabolism bacterial protein synthesis affected by, in LDL metabolism, 209, 210f
regulation of, 223
Anaerobic glycolysis, 136, 137f, 139 371–372 Apo C-I, 206, 206t
as muscle ATP source, 574–576, 575f, folate inhibitors as, 494 Apo C-II, 206, 206t
575t Antibodies, 580, 581. See also in lipoprotein lipase activity, 207–208
Apo C-III, 206, 206t
Analbuminemia, 584 Immunoglobulins lipoprotein lipase affected by, 208
Anaphylaxis, slow-reacting substance of, monoclonal, hybridomas in production Apo D, 206, 206t
Apo E, 206, 206t
196 of, 595–596, 596f receptors for
Anaplerotic reactions, in citric acid cycle, in xenobiotic cell injury, 631, 631f in chylomicron remnant uptake,
Antibody diversity, 591
133 DNA/gene rearrangement and, 593–594 208–209, 209f
Anchorin, in cartilage, 551t Antichymotrypsin, 583t in LDL metabolism, 209, 210f
Andersen’s disease, 152t Anticoagulants, coumarin, 604 Apoferritin, 586
Androgen response element, 459t Anticodon region, of tRNA, 359, 360, 360f Apolipoproteins/apoproteins, 205,
Androgens Antifolate drugs, purine nucleotide
205–206
estrogens produced from, 442–445, 444f synthesis affected by, 293 distribution of, 205–206, 206t
receptors for, 471 Antigenic determinant (epitope), 33, 591 hemoglobin; oxygenation affecting, 42
synthesis of, 440–442, 441f, 443f Antigenicity, xenobiotics altering, cell injury Apomyoglobin, hindered environment for
Androstenedione
estrone produced from, 444f, 445 and, 631, 631f heme iron and, 41, 41f
synthesis of, 442, 443f Antigens, 591 Apoproteins. See Apolipoproteins/
Anemias, 47 Antihemophilic factor A/globulin (factor
Fanconi’s, 338 apoproteins
hemolytic, 136, 143, 609, 619, 620t VIII), 599f, 600, 600t Apoptosis, 201
deficiency of, 604
glucose-6-phosphate dehydrogenase Antihemophilic factor B (factor IX), 599f, p53 and, 339
deficiency causing, 163, Apo-transketolase, activation of, in thiamin
169–170, 613, 614f, 619 600, 600t
coumarin drugs affecting, 604 nutritional status assessment, 489
haptoglobin levels in, 584 deficiency of, 604 APP. See Amyloid precursor protein
hyperbilirubinemia/jaundice in, 282, Antimalarial drugs, folate inhibitors as, Apurinic endonuclease, in base excision-

284, 284t 494 repair, 337
pentose phosphate pathway/ Antimycin A, respiratory chain affected by, Apyrimidinic endonuclease, in base

glutathione peroxidase and, 166, 95, 96f excision-repair, 337
167f, 169–170 Antioxidants, 91, 119, 611–613, 613t Aquaporins, 424–426
primaquine-sensitive, 613 D-Arabinose, 104f, 105t
red cell membrane abnormalities retinoids and carotenoids as, 119, 482t Arabinosyl cytosine (cytarabine), 290
causing, 619 vitamin C as, 119 Arachidonic acid/arachidonate, 113t, 190,
iron deficiency, 478, 497, 586, 610t vitamin E as, 91, 119, 486, 487f
megaloblastic Antiparallel loops, mRNA and tRNA, 360 190f
folate deficiency causing, 482t, 492, Antiparallel β sheet, 32, 33f eicosanoid formation and, 192, 193f,
494 Antiparallel strands, DNA, 303
vitamin B12 deficiency causing, 482t, Antiport systems, 426, 426f 194, 194f, 195f
492, 610t for nucleotide sugars, 517 for essential fatty acid deficiency,
pernicious, 482t, 492 α1-Antiproteinase (α1-antitrypsin), 583t,
recombinant erythropoietin for, 526, 610 191–192
sickle cell. See Sickle cell disease 589 ARC, 472t, 473
Angiotensin II, 437, 451, 452f deficiency of, 589–590, 589f, 590f, ARE. See Androgen response element
synthesis of, 451–452, 452f Argentaffinoma (carcinoid), serotonin in,
Angiotensin III, 452, 452f 623
Angiotensin-converting enzyme, 451–452, as thrombin inhibitor, 603 266–267
452f Antiproteinases, 623, 624t Arginase
Angiotensin-converting enzyme inhibitors, Antithrombin/antithrombin III, 583t,
451–452 in periodic hyperlysinemia, 258
Angiotensinogen, 451, 452f 603–604 in urea synthesis, 246f, 247
Anion exchange protein, 615, 615f, 616t heparin binding to, 547, 603–604 Arginine, 16t, 265, 266f
Ankyrin, 615f, 616f, 616t, 617 α1-Antitrypsin (α1-antiproteinase), 583t, catabolism of, 250, 251f
Anomeric carbon atom, 104 in urea synthesis, 246f, 247
Anomers, α and β, 104 589 Arginosuccinase
Anserine, 264, 265, 265f deficiency of, 589–590, 589f, 590f, deficiency of, 248
Antennae (oligosaccharide branches), 521 in urea synthesis, 246f, 247
Anterior pituitary gland hormones, blood 623–624 Arginosuccinate, in urea synthesis, 245,
glucose affected by, 161 as thrombin inhibitor, 603
APC. See Activated protein C 246f, 247
Apo A-I, 206, 206t, 224 Arginosuccinate synthase, 246f, 247
deficiencies of, 228t
Apo A-II, 206t deficiency of, 247
lipoprotein lipase affected by, 207–208 Arginosuccinicaciduria, 248

Aromatase enzyme complex, 442, 444f, 445 Asymmetry INDEX / 647
ARS (autonomously replicating sequences), importin binding and, 501
lipid and protein, membrane assembly ATP synthase, membrane-located, 96, 97f,
326, 413 and, 511, 512f 98f
Arsenate, oxidation and phosphorylation in membranes, 416, 419–420
Atractyloside, respiratory chain affected by,
affected by, 137, 142 Ataxia-telangiectasia, 338 95
Arterial wall, intima of, proteoglycans in, ATCase. See Aspartate transcarbamoylase
Atherosclerosis, 205, 607 Attachment proteins, 540, 541f
548 Autoantibodies, in myasthenia gravis, 431
Arthritis cholesterol and, 117, 219, 227 Autonomously replicating sequences (ARS),
HDL and, 210–211
gouty, 299 hyperhomocysteinemia and, folic acid 326, 413
proteoglycans in, 548 Auto-oxidation. See Peroxidation
rheumatoid, glycosylation alterations in, supplements in prevention of, Autoradiography, definition of, 413
494 Autotrophic organisms, 82
533 LDL receptor deficiency in, 209 Avidin, biotin deficiency caused by, 494
Artificial membranes, 421–422 lysophosphatidylcholine (lysolecithin) Axial ratios, 30
Ascorbate, 167, 168f and, 116 Axonemal dyneins, 577
Ascorbic acid (vitamin C), 163, 482t, Atorvastatin, 229 5- or 6-Azacytidine, 290
ATP, 82, 82–85, 287f, 289 8-Azaguanine, 290, 291f
495–496, 496f in active transport, 427–428, 428f Azathioprine, 290
as antioxidant, 119 in coupling, 82, 84 5- or 6-Azauridine, 290, 291f
in collagen synthesis, 38, 496, 535 fatty acid oxidation producing, 182
deficiency of, 482t, 496 free energy of hydrolysis of, 82–83, 82t B blood group substance, 618, 619f
in free energy transfer from exergonic to B (β) cells, pancreatic, insulin produced by,
collagen affected in, 38–39, 496, endergonic processes, 82–83, 82f
538–539 hydrolysis of 160
in muscle contraction, 561–562, 561f B cyclins, 333, 334f, 335t
iron absorption and, 478, 496 by NSF, 509, 510f B gene, Gal transferase encoded by,
supplemental, 496 inorganic pyrophosphate production
Asialoglycoprotein receptors and, 85 618–619
in cotranslational insertion, 506, 506f in mitochondrial protein synthesis and B lymphocytes, 591
in glycoprotein clearance, 517 import, 499
Asn-GlcNAc linkage in muscle/muscle contraction, 556, in hybridoma production, 595–596, 596f
in glycoproteins, 521 561–562, 561f B vitamins. See Vitamin B complex
in glycosaminoglycans, 543 decrease in availability of, 564 BAC vector. See Bacterial artificial
Asparaginase, in amino acid nitrogen sources of, 573–574, 574–576, 575f,
575t chromosome (BAC) vector
catabolism, 245, 245f in purine synthesis, 293–294, 295f Bacteria
Asparagine, 15t respiratory control in maintenance of
supply of, 94–95, 97, 97t, 98f, intestinal, in bilirubin deconjugation, 281
in amino acid nitrogen catabolism, 245 134–135 transcription cycle in, 342–343, 342f
catabolism of, 249, 250f structure of, 83f Bacterial artificial chromosome (BAC)
synthesis of, 237–238, 238f synthesis of
Asparagine synthetase, 238, 238f ATP synthase in, 96, 97f, 98f vector, 401–402, 402t
Aspartate in citric acid cycle, 131f, 133, 142, for cloning in gene isolation, 635t
catabolism of, 249, 250f 143t in Human Genome project, 634
synthesis of, 237–238, 238f glucose oxidation yielding, 142, 143t Bacterial gyrase, 306
in urea synthesis, 246f, 247 respiratory chain in, 93–95, 98f Bacterial promoters, in transcription,
Aspartate 102, in covalent catalysis, 53–54, ATP/ADP cycle, 83, 84f
ATPase 345–346, 345f
54f in active transport, 427–428, 428f Bacteriophage, definition of, 413
Aspartate aminotransferase (AST/SGOT), chaperones exhibiting activity of, 508 Bacteriophage lambda (λ), 378–383, 379f,
copper-binding P-type, mutations in
diagnostic significance of, 57t gene for 380f, 381f, 382f
Aspartate transcarbamoylase, 75 Menkes diseases caused by, 588 BAL. See Dimercaprol
Wilson disease caused by, 588–589 BAL 31 nuclease, in recombinant DNA
in pyrimidine synthesis, 298f, 299 ATP-binding cassette transporter-1, 210,
Aspartic acid, 15t 211f technology, 400t
ATP-chaperone complex, 508. See also Balanced chemical equations, 60
pI of, 17 Chaperones BamHI, 398, 399t
Aspartic protease family, in acid-base ATP-citrate lyase, 134, 135f, 156t, 157 Barbiturates, respiratory chain affected by,
acetyl-CoA for lipogenesis and, 177
catalysis, 52, 53f 95, 96f
Aspartylglycosaminuria, 532–533, 533t Basal lamina, laminin as component of,
Aspirin
540–542
antiplatelet actions of, 607–608 Basal metabolic rate, 478
cyclooxygenase affected by, 193 Base excision-repair of DNA, 336t, 337,
prostaglandins affected by, 190
Assembly particles, in absorptive 337f
Base pairing in DNA, 7, 303, 304, 305f
pinocytosis, 430
AST. See Aspartate aminotransferase matching of for renaturation, 305–306
Asthma, leukotrienes in, 112 recombinant DNA technology and,
Asymmetric substitution, in porphyrins,
396–397
270, 271f replication/synthesis and, 328–330, 330f

648 / INDEX Bilirubin Blood cells, 609–625. See also Erythrocytes;
accumulation of (hyperbilirubinemia), Neutrophils; Platelets
Base substitution, mutations occurring by, 281–284, 284t
361, 361f, 362 conjugated Blood clotting. See Coagulation
binding to albumin and, 283 Blood glucose
Basement membranes, collagen in, 537 reduction of to urobilinogen, 281,
Bases 282f normal, 145
conjugation of, 280, 280f, 281f regulation of
conjugate, 10 fecal, in jaundice, 284t
as proton acceptors, 9 heme catabolism producing, 278–280, clinical aspects of, 161–162, 161f
strong, 9 279f diet/gluconeogenesis/glycogenolysis in,
weak, 9 liver uptake of, 280–281, 280f, 281f,
Bence Jones protein, 595 282f 158–161, 159f, 160f
Bends (protein conformation), 32–33, normal values for, 284t glucagon in, 160–161
secretion of into bile, 280, 281f glucokinase in, 159–160, 160f
34f unconjugated, disorders occurring in, glycogen in, 145
Beriberi, 482t, 489 282–283 insulin in, 160
Beta-alanine. See β-Alanine urine, in jaundice, 284, 284t limits of, 158
Beta anomers, 104 metabolic and hormonal mechanisms
Beta- (β) carotene, 482, 482t, 483, 483f. Biliverdin, 278, 279f
Biliverdin reductase, 278 in, 159, 160t, 161
See also Vitamin A Bimolecular membrane layer, 418–419. See Blood group substances, 618, 619f
as antioxidant, 119, 482t
Beta-endorphins, 453, 453f also Lipid bilayer glycoproteins as, 514, 618
Beta-globin gene Binding constant, Michaelis constant (Km) Blood group systems, 617–619, 619f
localization of, 407t Blood plasma. See Plasma
recombinant DNA technology in approximating, 66 Blood type, 617–618
Binding proteins, 454–455, 454t, 455t, 583t Blood vessels, nitric oxide affecting,
detection of variations in, Biochemistry
407–408, 408f, 409t 571–573, 573f, 574t
Beta-lipoproteins, 205. See also low density as basis of health/disease, 2–4, 3t Blot transfer techniques, 403, 404f
lipoproteins definition of, 1 Blunt end ligation/blunt-ended DNA, 398,
Beta-oxidation of fatty acids, 181–183, Human Genome Project and, 3–4
181f, 182f methods and preparations used in, 1, 2t 399–400, 400f, 413
ketogenesis regulation and, 186–187, relationship of to medicine, 1–4, 3f BMR. See Basal metabolic rate
187f, 188f Biocytin, 494, 495f Body mass index, 478
modified, 183, 183f Bioenergetics, 80–85. See also ATP Body water. See Water
Beta (β) sheet, 32, 33f Bioinformatics, 412, 638 Bohr effect, 44, 45f
Beta subunits of hemoglobin, myoglobin protein function and, 28–29
and, 42 Biologic oxidation. See also Oxidation in hemoglobin M, 46
Beta (β) thalassemia, 47 Biomolecules. See also specific type Bone, 549–550, 549f, 550f
Beta (β) turn, 32, 34f stabilization of, 7
BFU-E. See Burst-forming unit-erythroid water affecting structure of, 6–7, 6t metabolic and genetic disorders
BgIII, 399t Biotechnology, Human Genome Project involving, 551–552, 551t
BHA. See Butylated hydroxyanisole
BHT. See Butylated hydroxytoluene affecting, 638 proteins in, 548t, 549
Bi-Bi reactions, 69–70, 69f, 70f Biotin, 482t, 494–495, 495f Bone Gla protein, 548t
Michaelis-Menten kinetics and, 70, 70f Bone marrow, heme synthesis in, 272
Bicarbonate, in extracellular and deficiency of, 482t, 494 Bone matrix Gla protein, 488
intracellular fluid, 416t in malonyl-CoA synthesis, 173, 174f Bone morphogenetic proteins, 548t
Biglycan as prosthetic group, 50 Bone sialoprotein, 548t
in bone, 548t BiP. See Immunoglobulin heavy chain Bone SPARC protein, 548t
in cartilage, 551t Botulinum B toxin, 511
Bilayers, lipid, 418–419, 418f, 419f binding protein Bovine spongiform encephalopathy, 37
membrane proteins and, 419 1,3-Bisphosphoglycerate (BPG), free energy BPG. See 1,3-Bisphosphoglycerate;
Bile, bilirubin secretion into, 280, 281f
Bile acids (salts), 225–227 of hydrolysis of, 82t 2,3-Bisphosphoglycerate
enterohepatic circulation of, 227 2,3-Bisphosphoglycerate (BPG), T structure Bradykinin, in inflammation, 621
in lipid digestion and absorption, 475, Brain, metabolism in, 235t
476f of hemoglobin stabilized by, 45,
secondary, 226f, 227 45f glucose as necessity for, 232
synthesis of, 225–227, 226f Bisphosphoglycerate mutase, in glycolysis in Branched chain amino acids, catabolism of,
regulation of, 226, 226f, 227 erythrocytes, 140, 140f
Bile pigments, 278–284, 282f. See also 2,3-Bisphosphoglycerate phosphatase, in 259, 260f, 261f, 262f
Bilirubin erythrocytes, 140, 140f disorders of, 259–262
Biliary obstruction, Blindness, vitamin A deficiency causing, 483 Branched-chain α-keto acid dehydrogenase,
hyperbilirubinemia/jaundice Blood
caused by, 283, 284, 284t coagulation of, 598–608. See also 259
Coagulation; Coagulation factors Branched chain ketonuria (maple syrup
functions of, 580, 581t
urine disease), 259
Branching enzymes

absence of, 152t
in glycogen biosynthesis, 145, 147f
Brefeldin A, 510–511
Brittle bones (osteogenesis imperfecta), 551t
Broad beta disease, 228t

Bronze diabetes, 587 in platelet activation, 606f, 607 INDEX / 649
Brown adipose tissue, 217, 217f as second messenger, 436–437, 437t,
Brush border enzymes, 475 in urea synthesis, 245, 246–247, 246f,
BSE. See Bovine spongiform encephalopathy 457, 463–465, 463t 247
Buffers phosphatidylinositide metabolism
Carbamoyl phosphate synthase I
Henderson-Hasselbalch equation affecting, 464–465, 464f, 465f deficiency of, 247
describing behavior of, 11, 12f vitamin D metabolism affected by, in urea synthesis, 245–246, 246f

weak acids and their salts as, 11–12, 12f 485–486 Carbamoyl phosphate synthase II, in pyrim-
“Bulk flow,” of membrane proteins, 507 Calcium ATPase, 463, 568 idine synthesis, 296, 298f, 299
Burst-forming unit-erythroid, 610, 611f Calcium-binding proteins, vitamin K and
Butylated hydroxyanisole (BHA), as Carbohydrates, 102–110. See also specific
glutamate carboxylation and type and Glucose; Sugars
antioxidant/food preservative, 119 postsynthetic modification
Butylated hydroxytoluene (BHT), as and, 487–488, 488f in cell membranes, 110
cell surface, glycolipids and, 116
antioxidant/food preservative, 119 synthesis and, 488, 604 classification of, 102, 102t
Butyric acid, 112t Calcium/calmodulin, 463 complex (glycoconjugate), glycoproteins
Calcium/calmodulin-sensitive phosphorylase
C1–9 (complement proteins), 596 as, 514
C-peptide, 449, 450f kinase, in glycogenolysis, 148 digestion and absorption of, 474–475,
C20 polyunsaturated acids, eicosanoids Calcium channels, 463. See also Calcium
475f
formed from, 190, 192, 193f, release channel interconvertibility of, 231
194f in cardiac muscle, 566–567 isomerism of, 102–104, 103f
C-reactive protein, 583, 583t Calcium-induced calcium release, in cardiac in lipoproteins, 110
C regions/segments. See Constant metabolism of, 122–123, 122f, 123f,
regions/segments muscle, 567
Ca2+ ATPase, 463 Calcium pump, 463, 568 124–125, 125f
Ca2+-Na+ exchanger, 463, 567–568 Calcium release channel diseases associated with, 102
Cachexia, cancer, 136, 479 vitamin B1 (thiamin) in, 488–489,
Caffeine, 289, 289f dihydropyridine receptor and, 563–564,
hormonal regulation of lipolysis and, 215 563f 489f
Calbindin, 477 in proteoglycans, 542, 543, 543f
Calcidiol (25-hydroxycholecalciferol), in mutations in gene for, malignant Carbon dioxide
vitamin D metabolism, 484, 485f hyperthermia caused by, citric acid cycle in production of,
Calciferol. See Vitamin D 564–565, 565f, 630t
Calcineurin, 566t 130–133, 132f
Calcinosis, 486 Calcium release channel, 563, 564f transport of, by hemoglobin, 44, 45f
Calcitonin, 437 Calcium-sodium exchanger, 463 Carbon monoxide
Calcitriol (1,25(OH)2-D3), 437, 439f, 485 Caldesmon, 571 heme catabolism producing, 278
calcium concentration regulated by, 485 Calmodulin, 463, 463t, 562 oxidative phosphorylation/respiratory
storage/secretion of, 453, 454t
synthesis of, 445, 446f, 484, 485f muscle phosphorylase and, 148, 149f chain affected by, 92, 95, 96f
Calcium, 496t Calmodulin-4Ca2+, in smooth muscle Carbon skeleton, amino acid. See Amino
absorption of, 477
vitamin D metabolism and, 477, 484, contraction, 570–571, 571f acid carbon skeletons
484–485 Calnexin, 508, 526 Carbonic acid, pK/pKa value of, 12t
in blood coagulation, 599f, 600, 600t, Calreticulin, 508, 526 Carbonic anhydrase, in osteopetrosis, 552
601 Calsequestrin, 563, 563f Carboxybiotin, 494, 495f
in bone, 549 cAMP. See Cyclic AMP γ-Carboxyglutamate, vitamin K in synthesis
in extracellular fluid, 416, 416t Cancer/cancer cells. See also
in intracellular fluid, 416, 416t of, 487, 488f
iron absorption affected by, 478 Carcinogenesis/carcinogens Carboxyl terminal repeat domain, 350
in malignant hyperthermia, 564–565, cyclins and, 334 Carboxylase enzymes, biotin as coenzyme
565f glycoproteins and, 514, 526, 530t, 531
metabolism of, 463 hormone-dependent, vitamin B6 of, 494–495
vitamin D metabolism and, 484–485 Carboxypeptidases, 477
in muscle contraction, 562 deficiency and, 491 Carboxyproteinase, procollagen, 537
in cardiac muscle, 566–568 membrane abnormalities and, 432t Carcinogenesis/carcinogens, 631
phosphorylase activation and, 148 mucins produced by, 520
sarcoplasmic reticulum and, 563–564, Cancer cachexia, 136, 479 chemical, 631
563f, 564f Cancer chemotherapy cytochrome P450 induction and, 628
in smooth muscle, 570, 571 folate inhibitors in, 494 indirect, 631
neutropenia caused by, 610 Carcinoid (argentaffinoma), serotonin in,
synthetic nucleotide analogs in,
266–267
290–291, 291f Carcinoid syndrome, 490
Cancer phototherapy, porphyrins in, Cardiac developmental defects, 570
Cardiac glycosides, 106
273 Cardiac muscle, 556, 566–570, 568t, 569t
CAP. See Catabolite gene activator protein Cardiolipin, 115, 115f
Caproic acid, 112t
Carbamates, hemoglobin, 44 synthesis of, 197, 197f, 199, 199f
Carbamoyl phosphate Cardiomyopathies, 556, 569–570, 569t
Cargo proteins/molecules, 510
excess, 301
free energy of hydrolysis of, 82t in export, 503
in import, 501, 502f

650 / INDEX factors affecting rates of, 61–63, 62f, CDK-cyclin inhibitor/CDKI, DNA/-
63–64, 64f chromosome integrity and, 339
Carnitine
deficiency of, 180, 187 free energy changes and, 60–61 CDKs. See Cyclin-dependent protein
in fatty acid transport, 180–181, 181f initial velocity and, 64 kinases
multiple substrates and, 69–70, 69f,
Carnitine-acylcarnitine translocase, 180, cDNA, 413
181f 70f sequencing, in glycoprotein analysis, 515t
substrate concentration and, 64, 64f,
Carnitine palmitoyltransferase, deficiency cDNA library, 402, 413
of, 180 65f CDRs. See Complementarity-determining
models of, 65–67, 66f, 67f
Carnitine palmitoyltransferase-I, 180, transition states and, 61 regions
181f mechanisms of, 51–52, 52f Celiac disease, 474
prosthetic groups/cofactors/coenzymes Cell, 1
deficiency of, 187
in ketogenesis regulation, 186–187, 187f, in, 50–51, 51f injury to
site-directed mutagenesis in study of, oxygen species causing, 611–613,
188f 613t
Carnitine palmitoyltransferase-II, 181, 181f 58 xenobiotics causing, 631, 631f
oxaloacetate and, 130
deficiency of, 187–188 ping-pong, 69–70, 69f lysis of, complement in, 596
Carnosinase deficiency, 264 prosthetic groups in, 50–51, 51f in macromolecule transport, 428–431,
Carnosine, 264, 265, 265f by proximity, 51
Carnosinuria, 264 regulation of, 72–79, 128f, 129 429f, 430f
β-Carotene, 482, 482t, 483, 483f. See also Cell adhesion
active and passive processes in, 72, 73f
Vitamin A allosteric, 74, 74–76, 75f, 128f, 129 fibronectin in, 540, 541f
as antioxidant, 119, 482t compartmentation in, 72–73 glycosphingolipids in, 202
Carotene dioxygenase, 482–483, 483f covalent, 74, 76, 77–78, 78f integrins in, 620–621, 622t
Carotenoids, 482–484, 483f, 484f. See also enzyme quantity and, 73–74 selectins in, 528–529, 529t, 530f
feedback inhibition and, 74–76, 75f, Cell biology, 1
Vitamin A Cell-cell interactions, 415
Carrier proteins/systems, 426, 426f 76, 129 mucins in, 520
feedback regulation and, 76, 129 Cell cycle, S phase of, DNA synthesis
for nucleotide sugars, 517 metabolite flow and, 72, 73f
Cartilage, 543, 551t, 552–553, 553f Michaelis constant (Km) in, 72, 73f during, 333–335, 334f, 335t
phosphorylation-dephosphorylation Cell death, 201
chondrodysplasia affecting, 553–554 Cell-free systems, vesicles studied in, 509
Catabolic pathways/catabolism, 81, 122. in, 78–79, 78t Cell fusion, 595
proteolysis in, 76–77, 77f Cell-mediated immunity, 591
See also Exergonic reaction; second messengers in, 76 Cell membrane. See Plasma membrane
Metabolism RNA and, 356 Cell migration, fibronectin in, 540
Catabolite gene activator protein (cyclic sequential (single) displacement, 69, 69f Cell recognition, glycosphingolipids in, 202
AMP regulatory protein), 376, specificity of, 49, 50f Cell sap. See Cytosol
378 by strain, 52 Cell surface carbohydrates, glycolipids and,
Catabolite regulatory protein, 460 substrate concentration affecting rate of,
Catalase, 88–89 116
as antioxidant, 119, 611–613, 613t 64, 64f, 65f Cell surfaces, heparan sulfate on, 545
in nitrogen metabolism, 244, 244f Hill model of, 66–67, 67f Cellulose, 109
Catalysis/catalytic reactions (enzymatic). See Michaelis-Menten model of, 65–66, Cellulose acetate zone electrophoresis, 580,
also Metabolism
acid-base, 51–52 66f 582f
HIV protease in, 52, 53f Catalytic residues, conserved, 54, 55t Central core disease, 565, 569t
at active site, 51, 51f Catalytic site, 75. See also Active site Central nervous system, glucose as
Bi-Bi, 69–70, 69f, 70f Cataracts, diabetic, 172
Michaelis-Menten kinetics and, 70, Catecholamines. See also specific type metabolic necessity for, 232
70f Centromere, 318, 319f
coenzymes/cofactors in, 50–51, 51f receptors for, 436 Cephalin (phosphatidylethanolamine), 115,
conservation of residues and, 54, 55t storage/secretion of, 453, 454t
covalent, 52, 52f, 63 synthesis of, 445–447, 447f 115f
chymotrypsin in, 52–54, 54f, 63 Cathepsins, in acid-base catalysis, 52 membrane asymmetry and, 420
fructose-2,6-bisphosphatase in, 54, 55f Caveolae, 422 synthesis of, 197, 197f
double displacement, 69–70, 69f Caveolin-1, 422 Ceramide, 116, 116f, 201–202, 202f, 203f
enzyme detection facilitated by, 55–56, CBG. See Corticosteroid-binding globulin synthesis of, 201–202, 202f
56f CBP/CBP/p300 (CREB-binding protein), Cerebrohepatorenal (Zellweger) syndrome,
equilibrium constant and, 63
isozymes and, 54–55 461, 468, 469, 469f, 471–472, 188, 503, 503t
kinetics of, 63–70 472t Cerebrosides, 201
activation energy and, 61, 63 CD11a-c/CD18, in neutrophils, 621, 621t Ceruloplasmin, 583t, 587, 588
balanced equations and, 60 CD18, 620–621
competitive versus noncompetitive CD49a/e/f, 622t deficiency of, 589
inhibition and, 67–69, 67f, CD59, 531 diagnostic significance of, 57t, 587
68f, 69f Cervonic acid, 113t
CFTR. See Cystic fibrosis transmembrane

regulator

CFU-E. See Colony-forming unit-erythroid in lipoprotein, 205, 207f INDEX / 651
Chain elongation. See also Elongation in membranes, 417
reconstitution of, in DNA replication,
by DNA polymerase, 328 fluid mosaic model and, 422 333
in glycosaminoglycan synthesis, 543 metabolism of, 123–124, 123f
in transcription cycle, 342, 342f remodeling of in gene expression,
Chain initiation. See also Initiation clinical aspects of, 227–229, 228t 383–384
in transcription cycle, 342, 342f diurnal variations in, 220
Chain termination. See also Termination high-density lipoproteins in, Chromatography. See also specific type
in glycosaminoglycan synthesis, 543 affinity
in transcription cycle, 342, 342f 209–211, 211f for protein/peptide purification, 23
Channeling, in citric acid cycle, 130 plasma levels of for recombinant fusion protein
Channelopathies, 568, 569t purification, 58, 59f
Chaperones, 36–37, 507–508, 508t atherosclerosis and coronary heart for protein/peptide purification, 21–24
ATPase activity of, 508 disease and, 227 Sepharose-lectin column, for
ATP-dependent protein binding to, 499, glycoprotein analysis, 515t
dietary changes affecting, 227
508 drug therapy affecting, 229 Chromium, 496t
histone, 315 lifestyle changes affecting, 227–229 Chromosomal integration, 324, 324f
in protein sorting, 499, 508t normal, 223 Chromosomal recombination, 323–324,
Chaperonins, 36–37 synthesis of, 219–220, 220f, 221f, 222f
Charging, in protein synthesis, 360, 360f acetyl-CoA in, 123f, 124, 219–220, 323f, 324f
Checkpoint controls, 339 Chromosomal transposition, 324–325
Chédiak-Higashi syndrome, 512t 220f, 221f, 222f Chromosome jumping, 635t
Chemical carcinogenesis/carcinogens, 631 carbohydrate metabolism and, 123 Chromosome walking, 411, 411f, 635t
Chemiosmotic theory, 92, 95–97, 97f HMG-CoA reductase in regulation of, Chromosomes, 318–319, 319f, 319t, 320f,
experimental findings in support of, 96
respiratory control and uncouplers and, 220, 223f 321f
in tissues, 118, 119f integrity of, monitoring, 339
97 interphase, chromatin fibers in, 316
Chemotactic factors, 620 factors affecting balance of, 220–223, metaphase, 317f, 318, 319t
Chemotherapy, cancer 224f polytene, 318, 318f
variations in, 636
folate inhibitors in, 494 transport of, 223–224, 225f Chronic granulomatous disease, 623, 623f
neutropenia caused by, 610 reverse, 210, 211f, 219, 224 Chyle, 207
synthetic nucleotide analogs in, Chylomicron remnants, 206t, 208, 209f
Cholesteryl ester hydrolase, 223 liver uptake of, 208–209
290–291, 291f Cholesteryl ester transfer protein, 224, 225f Chylomicrons, 125, 205, 206t
Chenodeoxycholic acid, 225, 226f Cholesteryl esters, 118, 205, 224 apolipoproteins of, 206, 206t
Chenodeoxycholyl CoA, 226, 226f metabolism of, 125, 126f, 207–209,
Chimeric gene approach, 385–386, 387f, in lipoprotein core, 205, 207f
Cholestyramine resins, for 209f
388f in triacylglycerol transport, 207, 208f,
Chimeric molecules, 397–406, 413 hypercholesterolemia, 229
Cholic acid, 225 209f
restriction enzymes and DNA ligase in Choline, 114–115, 115f Chymotrypsin, 477
preparation of, 399–400, 401f
deficiency of, fatty liver and, 212 conserved residues and, 55t
Chips, gene array, protein expression and, in glycine synthesis, 238, 239f in covalent catalysis, 52–54, 54f
28 membrane asymmetry and, 420 in digestion, 477
Cholinesterase. See Acetylcholinesterase for polypeptide cleavage, 26t
Chitin, 109, 109f Choluric jaundice, 282 Chymotrypsinogen, 477
Chloride Cholyl CoA, in bile acid synthesis, 226, cI repressor protein/cI repressor gene,

in extracellular and intracellular fluid, 226f 379–383, 380f, 381f, 382f
416, 416t Chondrodysplasias, 551t, 553–554, 554f CICR. See Calcium-induced calcium release
Chondroitin sulfates, 109, 109f, 538, Cirrhosis of liver, 130, 212
permeability coefficient of, 419f
Chlorophyll, 270 543–545, 544f, 544t in α1-antitrypsin deficiency, 590
Cholecalciferol (vitamin D3) functions of, 547 Cistron, 375–376
Chondronectin, 551t, 553 Citrate
synthesis of in skin, 445, 446f, 484, 485f Chorionic gonadotropin, human (hCG),
in vitamin D metabolism, 484, 485f in citric acid cycle, 130, 131f
Cholestatic jaundice, 283 438 in lipogenesis regulation, 178
Cholesterol, 117, 118, 119f, 205, 219–230 Christmas factor (factor IX), 599f, 600, 600t Citrate synthase, 130, 132f
in bile acid synthesis, 225–227, 226f Citric acid, pK/pKa value of, 12t
in calcitriol (1,25(OH)2-D3) synthesis, coumarin drugs affecting, 604 Citric acid cycle (Krebs/tricarboxylic acid
deficiency of, 604
445, 446f Chromatids cycle), 83, 130–135, 131f, 132f
dietary, 219 nucleoprotein packing in, 318, 319t, ATP generated by, 131f, 133, 142, 143t
excess of. See Hypercholesterolemia carbon dioxide liberated by, 130–133,
excretion of, 225–227, 226f 320f
in hormone synthesis, 438, 438–445, sister, 318, 319f 132f
deamination and, 133–134
439t, 440f exchanges between, 325, 325f gluconeogenesis and, 133, 134f,
Chromatin, 314–316, 315f, 315t
153–155, 154f
active vs. inactive regions of, 316–318,
318f

higher order structure/compaction of,
316, 317f

652 / INDEX vitamin K in, 486–488, 488f secretion of, 537
coumarin anticoagulants affecting, 604 triple helix structure of, 38, 38f,
Citric acid cycle (cont.)
in metabolism, 122, 122f, 123f, 124f, Coagulation factors, 600t. See also specific 535–539, 536f
126, 127f, 130, 133–135, 134f type under Factor types of, 535, 536t
amino acid, 122f, 124f Collision-induced dissociation, in mass
carbohydrate, 122–123, 122f, 123f, vitamin K in synthesis of, 486–488, 488f
133–134, 134f Coat proteins, recruitment of, 509, 510f spectrometry, 27
lipid/fatty acid, 122f, 123, 123f, 134, Coated pits, in absorptive pinocytosis, 429f, Collision (kinetic) theory, 61
135f Colon cancer. See Colorectal cancer
at subcellular level, 126, 127f 430 Colony-forming unit-erythroid, 610, 611f
in mitochondria, 126, 127f Coating, vesicle, 509, 510f Colony hybridization, 403–404. See also
reducing equivalents liberated by,
130–133, 132f brefeldin A affecting, 510–511 Hybridization
regulation of, 134–135 Cobalamin (vitamin B12), 482t, 491–492, Colorectal cancer, mismatch repair genes in,
respiratory chain substrates provided by,
130, 131f 492f 336
transamination and, 133–134, 134f absorption of, 491–492 Coltranslational glycosylation, 504
vitamins in, 133 Column chromatography, for protein/
intrinsic factor in, 477, 491–492
Citrulline, in urea synthesis, 245, 246–247, deficiency of, 482t, 492 peptide purification, 21, 22f
246f, 247 Combinatorial diversity, 592
functional folate deficiency and, 492, Compartmentation, 72–73
Citrullinemia, 247 494 Competitive inhibition, noncompetitive
CJD. See Creutzfeldt-Jakob disease
Cl. See Chloride in methylmalonic aciduria, 155 inhibition differentiated from,
Class B scavenger receptor B1, 210, 211f Cobalophilin, 492 67–69, 67f, 68f, 69f
Class (isotype) switching, 594 Cobalt, 496t Complement, 583t, 596–597
Classic pathway, of complement activation, in inflammation, 596, 621t
in vitamin B12 Complementarity
596 Cobamide, coenzymes derived from, 51 of DNA, 306, 307f
Clathrin, 429f, 430 Coding regions, 319, 321f, 637 recombinant DNA technology and,
Clathrin-coated vesicles, 510 396–397
Cleavage, in protein sequencing, 25, 26t in recombinant DNA technology, 397, of RNA, 306, 309f
CLIP, 453, 453f 398f Complementarity-determining regions,
Clofibrate, 229 591–592, 594f
Clones Coding strand, 304 Complementary DNA (cDNA), 413
in RNA synthesis, 341 Complementary DNA (cDNA) library,
definition of, 413 402, 413
library of, 402, 413 Codon usage tables, 359–360 Complex (glycoconjugate) carbohydrates,
in monoclonal antibody production, 596 Codons, 358, 359t glycoproteins as, 514
Cloning, 400–402, 401f, 402t, 403f Complex oligosaccharide chains, 521, 522f
in gene isolation, 635t amino acid sequence of encoded protein formation of, 521, 524
Cloning vectors, 400–402, 401f, 402t, specified by, 358 Concanavalin A (ConA), 110, 518t
Conformational diseases, 590
403f, 414 nonsense, 359 Congenital disorders of glycosylation
Closed complex, 345 Coenzyme A, synthesis of from pantothenic (CDG), 530t, 531
Clotting factors, 600t. See also specific type Congenital long QT syndrome, 432t
acid, 495, 495f Congenital nonhemolytic jaundice (type I
under Factor Coenzyme Q (Q/ubiquinone), 92, 95f Crigler-Najjar syndrome), 283
vitamin K in synthesis of, 486–488, 488f Coenzymes, 50 Conjugate acid, 10
CMP, 288t Conjugate base, 10
CMP-NeuAc, 516t, 517 in catalysis, 50–51, 51f Conjugation
CNBr. See Cyanogen bromide nucleotide derivatives, 290, 290t of bilirubin, 280, 280f, 281f
CO. See Carbon monoxide Cofactors, 50 of xenobiotics, 626, 628–630
CO2. See Carbon dioxide in blood coagulation, 600, 600t, 603 Connective tissue, 535
CoA. See Coenzyme A in catalysis, 50–51, 51f bone as, 549–550
Coactivators, transcription, 351, 351t in citric acid cycle regulation, 134–135 keratan sulfate I in, 545
Coagulation (blood), 598–608 Colipase, 475 Connexin, 431
endothelial cell products in, 607, 607t Collagen, 37–39, 371, 535–539, 536t Consensus sequences, 353, 353f
extrinsic pathway of, 598, 599f, 601 in bone, 548t, 549 Kozak, 365
fibrin formation in, 598–601, 599f in cartilage, 551t, 552, 553f Conservation of energy, 83
final common pathway in, 598, 599, classification of, 535, 536t Conserved residues, 54, 55t
elastin differentiated from, 539t Constant regions/segments, 593
601, 602f fibril formation by, 535–539, 536f, 537t gene for, 593
intrinsic pathway of, 598, 599f, 600–601 genes for, 535, 536t DNA rearrangement and, 325–326,
laboratory tests in evaluation of, 608 393, 593–594
prostaglandins in, 190 diseases caused by mutations in, 39,
proteins involved in, 599–600, 600t. See 538–539, 538t

also Coagulation factors chondrodysplasias, 551t, 553
osteogenesis imperfecta, 551
maturation/synthesis of, 38–39
ascorbic acid (vitamin C) in, 38, 496
disorders of, 38–39
O-glycosidic linkage in, 518
in platelet activation, 605, 606f, 607
posttranslational modification of,

537–538, 537t

immunoglobulin heavy chain, 591, 592f Corticotropin. See Adrenocorticotropic INDEX / 653
immunoglobulin light chain, 325–326, hormone
binding of to DNA, by helix-turn-helix
393, 591, 592f Cortisol, 439f, 440f motif, 389–390, 389f
Constitutive enzymes, 75 binding of, 454, 455, 455t
Constitutive gene expression, 376, 378 synthesis of, 440, 441f Cross-bridges, 557, 557–559, 558f, 562f
Constitutive heterochromatin, 316 Cross-links, covalent in collagen, 537
Constitutive mutation, 376 Cos sites, 401 Crossing-over, in chromosomal recombina-
Constitutive secretion, 498 Cosmids, 401, 402t, 413
Contig map, 634f tion, 323–324, 323f, 324f
Contractility/contraction. See Muscle for cloning in gene isolation, 635t Crouzon syndrome, 551t
Cothromboplastin (factor VII), 599f, 600t, CRP. See C-reactive protein; Catabolite
contraction
Cooperative binding 601 regulatory protein; Cyclic AMP
coumarin drugs affecting, 604 regulatory protein
hemoglobin, 42 Cotranslational insertion, 504, 505–506 Cryoprecipitates, recombinant DNA tech-
Bohr effect and, 44, 45f Cotransport systems, 426, 426f nology in production of, 604
Coulomb’s law, 5 Cryptoxanthin, 482
Hill equation describing, 66–67, 67f Coumarin, 604 Crystallography, x-ray, protein structure
COPI vesicles, 510 Coupling, 81–82, 81f, 82f demonstrated by, 35
COPII vesicles, 510 ATP in, 82, 84 CS-PG I/II/III, in bone, 548t
Coplanar atoms, partial double-bond hormone receptor-effector, 435–436 CT. See Calcitonin
Coupling domains, on hormone receptors, CTD. See Carboxyl terminal repeat domain
character and, 19, 20f CTP, 290
Copper, 496t 435–436 in phosphorylation, 85
Covalent bonds CY282Y mutation, in hemochromatosis, 587
ceruloplasmin in binding of, 587, 588 Cyanide, oxidative phosphorylation/
as cofactor, 588, 588t biologic molecules stabilized by, 6, 6t respiratory chain affected by, 92,
enzymes containing, 588t membrane lipid-protein interaction and, 95, 96f
in Menkes disease, 588 Cyanogen bromide, for polypeptide cleav-
metallothioneins in regulation of, 588 419 age, 25, 26t
in oxidases, 86 xenobiotic cell injury and, 631, 631f Cyclic AMP, 147, 148f, 289, 289f, 290t,
tests for disorders of metabolism of, 588, Covalent catalysis, 52, 52f, 63 458–462, 460t, 462f
chymotrypsin in, 52–54, 54f, 63 adenylyl cyclase affecting, 147, 458–459,
589t fructose-2,6-bisphosphatase in, 54, 55f 460t
in Wilson disease, 587, 588–589 Covalent cross-links, collagen, 537 in cardiac muscle regulation, 566
Copper-binding P-type ATPase, mutations Covalent modification in gluconeogenesis, 158, 158f
mass spectrometry in detection of, 27, in glycogen metabolism regulation,
in gene for 147–150, 148f, 149f, 150f
Menkes diseases caused by, 588 27f, 27t as second messenger, 147, 436, 437t,
Wilson disease caused by, 588–589 in protein maturation, 37–39 457, 458–462, 460t, 462f
Copper toxicosis, 588. See also Wilson in regulation of enzymatic catalysis, 74, smooth muscle contraction affected by,
571
disease 76, 77–78, 78f. See also Cyclic AMP-dependent protein kinase. See
Coproporphyrinogen I, 271, 275f Phosphorylation; Proteolysis Protein kinases
Coproporphyrinogen III, 271, 275f gluconeogenesis regulation and, 157 Cyclic AMP regulatory protein (catabolite
Coproporphyrinogen oxidase, 271, 275f, irreversible, 76–77, 77f gene activator protein), 376, 378
metabolite flow and, 79 Cyclic AMP response element, 459t, 461
276f reversible, 77–79, 78f, 78t Cyclic AMP response element binding
in porphyria, 277t CPT-I. See Carnitine palmitoyl protein, 461
Coproporphyrins, 272f transferase-I Cyclic GMP, 289f, 290
spectrophotometry in detection of, CRE. See Cyclic AMP response element as second messenger, 290, 436, 437t,
Creatine, 267, 268f 457, 462–463
273–274 Creatine kinase, diagnostic significance of, role in smooth muscle, 573f
Coprostanol (coprosterol), 225 57t Cyclic 3′,5′-nucleotide phosphodiesterase,
Core proteins, 542, 543f Creatine phosphate, 267, 268f in lipolysis, 215
free energy of hydrolysis of, 82t Cyclin-dependent protein kinases, 333,
in glycosaminoglycan synthesis, 542–543 in muscle, 573–574, 574–576, 575f, 334f, 335t
Coregulator proteins, 469, 471–473, 472f 575t inhibition of, DNA/chromosome
Corepressors, 472t, 473 Creatine phosphate shuttle, 100, 101f integrity and, 339
Cori cycle, 159, 159f Creatinine, 267, 268f Cyclins, 333–335, 334f, 335t
Cori’s disease, 152t CREB, 461 Cycloheximide, 372
Cornea, keratan sulfate I in, 545, 546, 547 CREB-binding protein, 461, 469, 469f, 471 Cyclooxygenase, 192
Coronary (ischemic) heart disease. See also Creutzfeldt-Jakob disease, 37 as “suicide enzyme,” 194
Crigler-Najjar syndrome Cyclooxygenase pathway, 192, 192–194,
Atherosclerosis type I (congenital nonhemolytic 193f, 194f
cholesterol and, 227 jaundice), 283
Corrinoids, 491. See also Cobalamin type II, 283
Corticosteroid-binding globulin (CBG/ Cro protein/cro gene, 379–383, 380f, 381f,
382f
transcortin), 454–455, 455t, 583t
cyclooxygenases affected by, 193
Corticosterone
binding of, 454, 455t
synthesis of, 438, 440, 441f

654 / INDEX Cytoskeleton/cytoskeletal proteins, 556, Delta4 (∆4) (progesterone) pathway, 442,
576–578 443f
CYP nomenclature, for cytochrome P450
isoforms, 627 red cell, 615f, 616–617, 616f, 616t Delta5 (∆5) (dehydroepiandrosterone)
Cytosol pathway, 442, 443f
CYP2A6, polymorphism of, 628, 630t
CYP2C9, in warfarin–phenobarbital ALA synthesis in, 270, 273f Delta9 (∆9) desaturase
glycolysis in, 126, 127f, 136 in monounsaturated fatty acid synthesis,
interaction, 628 lipogenesis in, 173–177, 174f, 175f 191, 191f
CYP2D6, polymorphism of, 628, 630t pentose phosphate pathway reactions in, in polyunsaturated fatty acid synthesis,
CYP2E1, enzyme induction and, 628 191, 191f
Cysteine, 15t, 265 163
pyrimidine synthesis in, 296, 298f Denaturation
metabolism of, 250, 252f, 253f Cytosolic branch, for protein sorting, 498, DNA structure analysis and, 304–305
abnormalities of, 250–255, 253f protein refolding and, 36
499f temperature and, 63
in pyruvate formation, 250, 252f Cytosolic dynein, 577
requirements for, 480 Cytosolic proteins, O-glycosidic linkages in, Deoxoynojirimycin, 527, 527t
synthesis of, 238–239, 239f Deoxyadenylate, 303
Cystic fibrosis, 431–432, 432t, 474, 569t 518 Deoxycholic acid, synthesis of, 226
Cystic fibrosis transmembrane regulator Cytotoxicity, xenobiotic, 631, 631f Deoxycorticosterone

(CFTR), 431, 431f, 432t D-amino acids, free, 14 binding of, 454–455
Cystine reductase, 250, 252f D arm, of tRNA, 310, 312f, 360, 361f synthesis of, 438, 441f
Cystinosis (cystine storage disease), D cyclins, 333, 334f, 335t 11-Deoxycortisol, synthesis of, 440, 441f
Deoxycytidine residues, methylation of,
250–255 cancer and, 334
Cystinuria (cystine-lysinuria), 250 D isomerism, 102–104, 103f gene expression affected by, 383
Cytarabine (arabinosyl cytosine), 290 DAF. See Decay accelerating factor Deoxycytidylate, 303
Cytidine, 287f, 288t dAMP, 288f Deoxyguanylate, 303
Cytidine monophosphate (CMP), 288t Dantrolene, for malignant hyperthermia, Deoxyhemoglobin, proton binding by, 44,
Cytidine monophosphate
564 45f
N-acetylneuraminic acid DBD. See DNA-binding domain Deoxyhemoglobin A, “sticky patch” recep-
(CMP-NeuAc), 516t, 517 DBH. See Dopamine-β-hydroxylase
Cytidine triphosphate (CTP), 290 Deamination, 124, 124f tor on, 46
in phosphorylation, 85 Deoxyhemoglobin S, “sticky patch”
Cytochrome b5, 89, 627 citric acid cycle in, 133–134
Cytochrome b558, 622 liver in, 125 receptor on, 46
Cytochrome c, 93 Debranching enzymes Deoxynucleotides, 303–304, 304f, 305f
Cytochrome oxidase/cytochrome aa3, 86, absence of, 152t Deoxyribonucleases (DNase)/DNase I, 312
93 in glycogenolysis, 146–147, 148f
Cytochrome P450-dependent microsomal Debrisoquin, CYP2D6 in metabolism of, active chromatin and, 316
ethanol oxidizing system, Deoxyribonucleic acid. See DNA
212–214 628 Deoxyribonucleoside diphosphates
Cytochrome P450 side chain cleavage en- Decay accelerating factor, 531
zyme (P450scc), 438, 440f, 442 Decorin (dNDPs), reduction of NDPs to,
Cytochrome P450 system, 86, 89–90, 90f, 294, 297f
626 in bone, 548t Deoxyribonucleosides, 286
ALA synthase affected by, 272, 278 in cartilage, 551t in pyrimidine synthesis, 296
enzyme induction and, 272–273, Defensins, 621t Deoxyribose, 102, 106, 106f
627–628 Degeneracy, of genetic code, 359 Deoxy sugars, 106, 106f
genes encoding, nomenclature for, 627 Degradation, rate of (kdeg), 74 3-Deoxyuridine, 290
isoforms of, 627–628 Dehydrocholesterol, in vitamin D Dephosphorylation. See also
in metabolism of xenobiotics, 626–628, Phosphorylation
629t metabolism, 484, 485f in covalent modification, 78–79, 78t
membrane insertion, 504 Dehydroepiandrosterone (DHEA), Depolarization, in nerve impulse
mitochondrial, 89–90 transmission, 428
nomenclature system for, 627 synthesis of, 440, 441f Depurination, DNA, base excision-repair
in xenobiotic cell injury, 631, 631f Dehydroepiandrosterone (∆5) pathway, 442, and, 337
Cytochromes, as dehydrogenases, 88 Dermatan sulfate, 544f, 544t, 545
Cytogenetic abnormalities, detection of, 443f functions of, 547
635t Dehydrogenases, 86, 87–88, 88f ∆9 Desaturase
Cytogenetic map, 633, 634f in monounsaturated fatty acid synthesis,
Cytokines, α2-macroglobulin binding of, in enzyme detection, 56, 56f 191, 191f
590 nicotinamide coenzyme-dependent, 87, in polyunsaturated fatty acid synthesis,
Cytosine, 288t 191, 191f
base pairing of in DNA, 303, 304, 305f 89f Desmin, 566t, 577t
deoxyribonucleosides of, in pyrimidine in respiratory chain, 87 Desmosines, 539
synthesis, 296–297, 298f riboflavin-dependent, 87 Desmosterol, in cholesterol synthesis, 220,
Deletions, DNA, recombinant DNA tech- 222f
Detergents, 417–418
nology in detection of, 409,
409t
Delta5,4 (∆5,4) isomerase, 438, 441f, 442,
443f

Detoxification, 626 Dihydrobiopterin, defect in synthesis of, 255 INDEX / 655
cytochrome P450 system in, 89–90, 90f, Dihydrobiopterin reductase, defect in, 255
626–628, 629t Dihydrofolate/dihydrofolate reductase, Diversity
antibody, 592, 593–594
Dextrinosis, limit, 152t methotrexate affecting, 296–297, combinatorial, 592
Dextrins, 109 494 in gene expression, 387, 388f
Dextrose, 104 Dihydrolipoyl dehydrogenase, 140, 141f junctional, 593–594
DHA. See Docosahexaenoic acid Dihydrolipoyl transacetylase, 140, 141f
DHEA. See Dehydroepiandrosterone Dihydropyridine receptor, 563–564, 563f, Diversity segment, DNA rearrangement
DHPR. See Dihydropyridine receptor 564f and, 593–594
DHT. See Dihydrotestosterone Dihydrotestosterone, 442, 444f
Diabetes mellitus, 102, 161–162 binding of, 455t DNA, 303, 303–306, 314 –340
Dihydroxyacetone, 106f base excision-repair of, 336t, 337, 337f
fatty liver and, 212 Dihydroxyacetone phosphate, in glycolysis, base pairing in, 7, 303, 304, 305f
free fatty acid levels in, 206 197, 197f, 198f matching of for renaturation, 305–306
hemochromatosis and, 587 1,25-Dihydroxyvitamin D3. See Calcitriol recombinant DNA technology and,
insulin resistance and, 611 24,25-Dihydroxyvitamin D3 (24-hydroxy- 396–397
ketosis/ketoacidosis in, 188 calcidiol), in vitamin D replication/synthesis and, 328–330,
lipid transport and storage disorders and, metabolism, 484, 485f 330f
Diiodotyrosine (DIT), 447, 448f, 449 binding of to regulatory proteins, motifs
205 Dilated cardiomyopathy, 570 for, 387–390, 388t, 389f, 390f,
lipogenesis in, 173 Dimercaprol (BAL), respiratory chain 391f
as metabolic disease, 122, 231 affected by, 95, 96f blunt-ended, 398, 399–400, 400f, 413
starvation and, 236 Dimeric proteins, 34 in chromatin, 314 –318, 315f, 315t,
Diabetic cataract, 172 Dimers 317f, 318f
Diacylglycerol, 115, 475, 476f Cro protein, 380, 381f chromosomal, 318–319, 319f, 319t,
in calcium-dependent signal histone, 315 320f, 321f
lambda repressor (cI) protein, 380, 381f relationship of to mRNA, 321f
transduction, 464, 465f Dimethylallyl diphosphate, in cholesterol coding regions of, 319, 321f, 637
formation of, 197f, 198f synthesis, 219, 221f complementarity of, 306, 307f
in platelet activation, 606, 606f Dimethylaminoadenine, 289f recombinant DNA technology and,
in respiratory burst, 623 Dinitrophenol, respiratory chain affected 396–397
Diacylglycerol acyltransferase, 198f, 199 by, 95, 96f damage to, 335, 335t
Diagnostic enzymology, 57, 57t Dinucleotide, 291 repair of, 335–339, 335t, 336t
Dicarboxylate anions, transporter systems Dioxygenases, 89 ADP-ribosylation for, 490
Dipalmitoyl lecithin, 115 deletions in, recombinant DNA technol-
for, 98–99 Dipeptidases, 477 ogy in detection of, 409, 409t
Dicarboxylic aciduria, 188 Diphosphates, nucleoside, 287, 287f depurination of, base excision-repair and,
Dicumarol (4-hydroxydicoumarin), 486 Diphosphatidylglycerol. See Cardiolipin 337
Dielectric constant, of water, 5 Diphtheria toxin, 372 double-strand break repair of, 336t,
Diet. See also Nutrition Dipoles, water forming, 5, 6f 337–338, 338f
Disaccharidases, 102, 475 double-stranded, 304
blood glucose regulation and, 159–161 Disaccharides, 106–107, 107f, 107t. See flanking sequence, 397
cholesterol levels affected by, 227 also specific type genetic information contained in,
hepatic VLDL secretion and, 211–212, Disease 303 –306
biochemical basis of, 2, 3t grooves in, 305f, 306
213f Human Genome Project and, 3–4 insertions in, recombinant DNA
high-fat, fatty liver and, 212 major causes of, 3t technology in detection of, 409
Diet-induced thermogenesis, 217, 478 Displacement reactions integrity of, monitoring, 339
Diethylenetriaminepentaacetate (DTPA), double, 69–70, 69f “jumping,” 325
sequential (single), 69, 69f mismatch repair of, 36f, 336, 336f,
as preventive antioxidant, 119 Dissociation, of water, 8–9 336t
Diffusion Dissociation constant, 8–9 mitochondrial, 322–323, 322f, 323t
Michaelis constant (Km) and, 66 mutations in, 314, 323 –326, 323f, 324f,
facilitated, 423, 423t, 424f, 426–427, in pH calculation, 10 325f. See also Mutations
427, 427f of weak acids, 10–11, 12 in nucleosomes, 315–316, 316f
Distal histidine (histidine E7), in oxygen nucleotide excision-repair of, 336, 337,
of bilirubin, 280 binding, 40, 41f 338f
of glucose. See also Glucose Disulfide bonds, protein folding and, 37 rearrangements of
DIT. See Diiodotyrosine in antibody diversity, 325–326, 393,
transporters Diurnal rhythm, in cholesterol synthesis, 593–594
insulin affecting, 427 220 recombinant DNA technology in
in red cell membrane, 611 detection of, 409, 409t
hormones in regulation of, 427 recombinant. See Recombinant DNA/
“Ping-Pong” model of, 427, 427f recombinant DNA technology
net, 423, 424f
passive, 423, 423t, 424f
simple, 423, 423t, 424f
Digestion, 474–480
Digitalis
Ca2+-Na+ exchanger in action of, 568
Na+-K+ ATPase affected by, 428, 568

656 / INDEX DNA-PK. See DNA-dependent protein Dopamine, 446, 447f. See also Cate-
kinase cholamines
DNA (cont.)
relaxed form of, 306 DNA polymerases, 326, 327–328, 327f, synthesis of, 267, 267f, 445–447, 447f
renaturation of, base pair matching and, 328, 328t Dopamine-β-hydroxylase, 447
305–306
repair of, 335–339, 335t, 336t in recombinant DNA technology, 400t vitamin C as coenzyme for, 495–496
repetitive-sequence, 320–322 DNA primase, 327, 327f, 328t Dopamine β-oxidase, 267, 267f
replication/synthesis of, 306, 307f, DNA probes, 402, 414 Double displacement reactions, 69–70, 69f
326–339, 326t, 327f, 328t Double helix, of DNA structure, 7, 303,
DNA polymerase complex in, 328, for gene isolation, 635t
328t library searched with, 402 304, 305f
DNA primer in, 328, 329f, 330f in porphyria diagnosis, 274 recombinant DNA technology and, 396,
initiation of, 328–330, 329f, 330f, DNA-protein interactions, bacteriophage
331f 397
origin of, 326 lambda as paradigm for, Double reciprocal plot
polarity of, 330–331 378–383, 379f, 380f, 381f, 382f
proteins involved in, 328t DNA sequences inhibitor evaluation and, 68, 68f, 69f
reconstitution of chromatin structure amplification of by PCR, 405–406, Km and Vmax estimated from, 66, 66f
and, 333 406f Double-strand break repair of DNA, 336t,
repair during, 335–339, 335t, 336t determination of, 404, 405f
replication bubble formation and, in gene isolation, 635t 337–338, 338f
331–333, 331f, 332f, 333f protein sequencing and, 25–26 Double-stranded DNA, 304, 314
replication fork formation and, DNA topoisomerases, 306, 328t, 332,
327–328, 327f 332f unwinding
ribonucleoside diphosphate reduction DNA transfection, identification of for replication, 326, 326–327
and, 294, 297f enhancers/regulatory elements RNA synthesis and, 344
in S phase of cell cycle, 333–335, and, 386
334f, 335t DNA unwinding element, 326 Downstream promoter element, 346–348,
semiconservative nature of, 306, 307f DNase (deoxyribonuclease)/DNase I, 312 347f
semidiscontinuous, 327f, 331, 331f active chromatin and, 316
unwinding and, 326, 326–327 in recombinant DNA technology, 400t DPE. See Downstream promoter element
in RNA synthesis, 341–343, 342f, 343t dNDPs. See Deoxyribonucleoside DRIPs, 472t, 473
stabilization of, 7 diphosphates Drug detoxification/interactions,
structure of, 303–306, 304f, 305f DOC. See 11-Deoxycorticosterone
denaturation in analysis of, 304–305 Docking, in nuclear import, 501, 502f cytochromes P450 and,
double-helical, 7, 303, 304, 305f Docking protein, 504 89–90, 90f, 628
recombinant DNA technology and, Docosahexaenoic acid, 191–192 Drug development, pharmacogenetics and,
396, 397 Dolichol, 118, 119f, 522, 523f 631–632
supercoiled, 306, 332, 333f in cholesterol synthesis, 220, 221f Drug resistance, gene amplification in, 393
transcription of, 306 in N-glycosylation, 522 DS-PG I/DS-PG II, in cartilage, 551t
transposition of, 325 Dolichol kinase, 522 dsDNA. See Double-stranded DNA
unique-sequence (nonrepetitive), 320, Dolichol-P-P-GlcNAc, 522–523 DTPA, as preventive antioxidant, 119
320–321 Dolichol-P-P-oligosaccharide (dolichol- Dubin-Johnson syndrome, 283
unwinding of, 326, 326–327 pyrophosphate-oligosaccharide), Duchenne muscular dystrophy, 556,
RNA synthesis and, 344 521, 524f 565–566, 566f
xenobiotic cell injury and, 631 in N-glycosylation, 521–524, 523f DUE. See DNA unwinding element
Dolichol phosphate, 522 Dwarfism, 551t, 553–554
DNA binding domains, 390–391, 392f, 470 Domains. See also specific type Dynamin, in absorptive pinocytosis, 430,
DNA binding motifs, 387–390, 388t, 389f, albumin, 584 577
carboxyl terminal repeat, 350 Dyneins, 577
390f, 391f chromatin, 316, 318, 319f Dysbetalipoproteinemia, familial, 228t
DNA-dependent protein kinase, in coupling, on hormone receptors, 435–436 Dyslipoproteinemias, 228t, 229
DNA binding, 390–391, 392f, 470 Dystrophin, 556, 565–566, 566t, 567f
double-strand break repair, 338 fibronectin, 540, 541f mutation in gene for, in muscular
DNA-dependent RNA polymerases, protein, 33–34 dystrophy, 565–566, 566f
Src homology 2 (SH2)
342–343, 342f, 343t in insulin signal transmission, 465, E0. See Redox (oxidation-reduction)
DNA elements, gene expression affected by, 466f, 467 potential
in Jak/STAT pathway, 467, 467f
384–385, 384f, 385t, 386f trans-activation, of regulatory proteins, Eact. See Activation energy
diversity and, 387, 388f 390–391, 392f E coli, lactose metabolism in, operon
DNA fingerprinting, 413 transcription, 387
DNA footprinting, 413 L-Dopa, 446, 447f hypothesis and, 376–378,
DNA helicase, 326–327, 327f, 328, 328t Dopa decarboxylase, 267, 267f, 446, 447f 376f, 377f
DNA ligase, 328t, 330 E coli bacteriophage P1-based (PAC) vector,
in recombinant DNA technology, 401–402, 402t, 413
E cyclins, 333, 334f, 335t
399–400, 400t, 401f E-selectin, 529t
E (exit) site, in protein synthesis, 38f, 368
ECF. See Extracellular fluid
ECM. See Extracellular matrix

EcoRI, 398, 399t, 401f in glycosaminoglycan synthesis, 543 INDEX / 657
EcoRII, 399t in protein synthesis, 367–370, 368f
Edema in RNA synthesis, 342, 342f, 344 neutrophil interaction and
Elongation arrest, 504 integrins in, 529t, 620–621, 622t
in kwashiorkor, 479 Elongation factor 2, in protein synthesis, selectins in, 528–529, 529t, 530f
plasma protein concentration and, 580
in thiamin deficiency, 489 368, 368f Endothelium-derived relaxing factor, 572,
Edman reaction, for peptide/protein Elongation factor EF1A, in protein 607t. See also Nitric oxide

sequencing, 25, 26f synthesis, 368, 368f Energy
Edman reagent (phenylisothiocyanate), in Elongation factors, in protein synthesis, activation, 61, 63
conservation of, 83
protein sequencing, 25, 26f 367, 368, 368f free. See Free energy
EDRF. See Endothelium-derived relaxing Emelin, 539 in muscle, creatine phosphate as reserve
Emphysema, α1-antiproteinase deficiency for, 573–574, 575f
factor nutritional requirement for, 478
EDTA, as preventive antioxidant, 119 and, 589, 589f, 623–624 transduction of
EFA. See Essential fatty acids Emulsions, amphipathic lipids forming, membranes in, 415
EFs. See Elongation factors in muscle, 556–559
EGF. See Epidermal growth factor 120f, 121
Egg white, uncooked, biotin deficiency Encephalopathies Energy balance, 478–479
Energy capture, 82–83, 82f, 83
caused by, 494 hyperbilirubinemia causing (kernicterus), Energy expenditure, 478
Ehlers-Danlos syndrome, 538, 538t 282, 283 Energy transfer, 82–83, 82f
Eicosanoids, 112, 190, 192, 193f, 194f, Enhanceosome, 385, 386f
mitochondrial, with lactic acidosis and Enhancers/enhancer elements, 348
621t stroke (MELAS), 100–101
Eicosapentaenoic acid, 190f in gene expression, 384–385, 384f, 385t
eIF-4E complex, in protein synthesis, 367, spongiform (prion diseases), 37 tissue-specific expression and, 385
Wernicke’s, 489
367f Endergonic reaction, 80, 81 recombinant DNA technology and, 397
eIFs, in protein synthesis, 365 coupling and, 81–82, 81f, 82f reporter genes in definition of, 385–386,
80S initiation complex, in protein synthesis,
ATP in, 82, 84 387f, 388f
366f, 367 Endocrine system, 434 – 455. See also Enolase, in glycolysis, 137, 138f
Elaidic acid, 112, 113, 113t, 114f ∆2Enoyl-CoA hydratase, 181, 182f
Elastase, in digestion, 477 Hormones ∆3cis-Enoyl-CoA isomerase, 183
Elastin, 539, 539t diversity of, 437– 438 ∆2trans-Enoyl-CoA isomerase, 183
Electrochemical potential difference, in Endocytosis, 428, 429–430, 429f Entactin, in basal lamina, 540
receptor-mediated, 429f Enterohepatic circulation, 227
oxidative phosphorylation, 96 Endoglycosidase F, 517
Electron carriers, flavin coenzymes as, 490 Endoglycosidase H, 517 lipid absorption and, 475
Electron movement, in active transport, 427 Endoglycosidases, in glycoprotein analysis, Enterohepatic urobilinogen cycle, 281
Electron-transferring flavoprotein, 87, 181 Enteropeptidase, 477
Electron transport chain system, 622. See 515t, 517, 517t Enthalpy, 80
Endonucleases, 312, 413 Entropy, 80
also Respiratory chain Enzyme induction, 630
Electrophiles, 7 apurinic and apyrimidinic, in base
Electrophoresis excision-repair, 337 cytochrome P450 and, 272–273,
627–628
for plasma protein analysis, 580 restriction, 312, 397–399, 399t, 400f,
polyacrylamide, for protein/peptide 414 in gluconeogenesis regulation, 155–157,
156t
purification, 24, 24f, 25f in recombinant DNA technology,
pulsed-field gel, for gene isolation, 635t 399–400, 399t, 400f, 400t, 401f Enzyme-linked immunoassays (ELISAs), 55
two-dimensional, protein expression and, Enzymes, 7–8
Endopeptidases, 477
28 Endoplasmic reticulum, 370 active sites of, 51, 51f
Electrospray dispersion, in mass assay of, 55–56, 56f
acylglycerol synthesis and, 126, 127f branching, in glycogen biosynthesis, 145,
spectrometry, 27 core protein synthesis in, 543
Electrostatic bonds/interactions, 7. See also fatty acid chain elongation in, 177, 177f 147f
rough catalytic activity of, 49, 50f. See also
Salt (electrostatic) bonds
oxygen binding rupturing, Bohr effect glycosylation in, 524–525, 525f Catalysis
in protein sorting, 498, 499f, 500f detection facilitated by, 55–56, 56f
protons and, 44–45, 45f protein synthesis and, 370 kinetics of, 63–70. See also Kinetics
ELISAs. See Enzyme-linked immunoassays routes of protein insertion into,
Elliptocytosis, hereditary, 617 (enzyme)
Elongase, 177, 177f 505–507, 506f regulation of, 72–79, 128f, 129
signal hypothesis of polyribosome RNA and, 356
in polyunsaturated fatty acid synthesis, specificity of, 49, 50f
191, 191f, 192f binding to, 503–505, 504t, 505f classification of, 49–50
smooth, cytochrome P450 isoforms in, constitutive, 75
Elongation debranching
chain 627 absence of, 152t
in fatty acid synthesis, 177, 177f Endoproteinase, for polypeptide cleavage, in glycogenolysis, 146–147, 148f
in transcription cycle, 342, 342f
in DNA synthesis, 328 26t
Endorphins, 453, 453f
Endothelial cells

in clotting and thrombosis, 607, 607t

658 / INDEX Erythrocytes, 609–610, 610–619 iron absorption and, 478
2,3-bisphosphoglycerate pathway in, thiamin deficiency and, 489
Enzymes (cont.) 140, 140f Ethylenediaminetetraacetate (EDTA), as
degradation of, control of, 74 disorders affecting, 609, 610t
in disease diagnosis/prognosis, 56 –57, erythropoietin in regulation of, 609–610, preventive antioxidant, 119
57, 57t, 58f, 580 611f Euchromatin, 316
in DNA repair, 335, 336t, 338–339 glucose-6-phosphate dehydrogenase defi- Eukaryotic gene expression, 383–387,
hydrolysis rate affected by, 7–8 ciency affecting, 613, 614f, 619
irreversible inhibition (“poisoning”) of, glucose as metabolic necessity for, 232 391–395, 392t. See also Gene
69 glycolysis in, 140, 140f expression
isozymes and, 54 –55 hemoglobin S “sticky patch” affecting, 46 chromatic remodeling in, 383–384
kinetics of, 60–71. See also Kinetics hemolysis of, pentose phosphate diversity of, 387, 388f
(enzyme) pathway/glutathione peroxidase DNA elements affecting, 384–385, 384f,
mechanisms of action of, 49–59 and, 166, 167f, 169–170 385t, 386f
membranes in localization of, 415 life span of, 609 DNA-protein interactions in, bacterio-
metal-activated, 50 membranes of, 614–617, 615f, 615t, phage lambda as paradigm for,
as mitochondrial compartment markers, 616f, 616t 378–383, 379f, 380f, 381f, 382f
92 glucose transporter of, 611, 612t locus control regions and insulators in,
plasma, diagnostic significance of, 57, 57t hemolytic anemias and, 619, 620t 387
quantity of, catalytic capacity affected by, metabolism of, 235t, 610–614, 612t prokaryotic gene expression compared
73–74 oxidants produced during, 611–613, with, 391–395, 392t
rate of degradation of (kdeg), control of, 613t reporter genes and, 385–386, 387f, 388f
74 recombinant DNA technology in study tissue-specific, 385
rate of synthesis of (ks), control of, 74 of, 624 Eukaryotic promoters, in transcription,
recombinant DNA technology in study structure and function of, 609–610 346–349, 347f, 348f, 349f
of, 58, 59f Eukaryotic transcription complex,
regulatory, 126–129, 128f Erythroid ALA synthase (ALAS2), 272, 273 350–352, 351t
restriction. See Restriction endonucleases in porphyria, 274, 277t Exchange transporters, 98–100, 98f, 99f
specificity of, 49, 50f Excitation-response coupling, membranes
substrates affecting conformation of, 52, Erythropoiesis, 609–610, 611f in, 415
53f Erythropoietin/recombinant erythropoietin Exergonic reaction, 80, 81
coupling and, 81–82, 81f, 82f
Enzymopathies, 619 (epoitin alfa/EPO), 526, 583t, ATP in, 82, 84
Epidermal growth factor (EGF), receptor 609–610, 611f Exinuclease, in DNA repair, 337, 337f
D-Erythrose, 104f Exit (E) site, in protein synthesis, 368,
for, 436 Escherichia coli, lactose metabolism in, 368f
Epidermolysis bullosa, 538, 538t operon hypothesis and, 376–378, Exocytosis, 429, 430–431, 430f
Epimerases 376f, 377f in insulin synthesis, 430–431
Escherichia coli bacteriophage P1-based Exocytotic (secretory) pathway, 498
in galactose metabolism, 167, 170f (PAC) vector, 401–402, 402t, Exoglycosidases, in glycoprotein analysis,
in glycosaminoglycan synthesis, 543 413 515t, 517, 517t
in pentose phosphate pathway, 163, 165f Essential amino acids. See Nutritionally Exons, 319, 358, 413
Epimers, 104, 104f essential amino acids interruptions in. See Introns
Epinephrine, 439f, 447, 447f. See also Essential fatty acids, 190, 190f, 193 in recombinant DNA technology, 397,
abnormal metabolism of, 195–196 398f
Catecholamines deficiency of, 191–192, 194–195 splicing, 352–354, 414
blood glucose affected by, 161 prostaglandin production and, 190 alternative, in regulation of gene
in gluconeogenesis regulation, 157 Essential fructosuria, 163, 171–172 expression, 354, 354f,
in lipogenesis regulation, 178 Essential pentosuria, 163, 170 393–394, 636
synthesis of, 267, 267f, 445–447, 447f Estradiol/17β-Estradiol, 439f, 440f recombinant DNA technology and,
Epitope (antigenic determinant), 33, 591 binding of, 455, 455t 397, 398f
Epoxide hydrolase, 631 synthesis of, 442–445, 444f Exonucleases, 312, 413
Epoxides, 631 Estriol, synthesis of, 442, 444f in recombinant DNA technology, 400t
Equilibrium constant (Keq), 62–63 Estrogen response element, 459t Exopeptidases, 477
in enzymatic catalysis, 63 Estrogens Exportins, 503
free energy changes and, 60–61 binding of, 455, 455t Expression vector, 402
ER. See Estrogens, receptors for receptors for, 471 Extra arm, of tRNA, 310, 312f
Ercalcitriol, 484 synthesis of, 442–445, 444f, 445f Extracellular environment, membranes in
ERE. See Estrogen response element Estrone maintenance of, 415–416, 416t
eRF. See Releasing factors binding of, 455t Extracellular fluid (ECF), 415–416, 416,
Ergocalciferol (vitamin D2), 484 synthesis of, 442, 444f 416t
Ergosterol, 118, 119f Ethanol Extracellular matrix, 535–555. See also spe-
Erythrocyte aminotransferases, in vitamin CYP2E1 induction and, 628 cific component and under Matrix
fatty liver and, 212–214
B6 status assessment, 491
Erythrocyte transketolase activation, in

thiamin nutritional status
assessment, 489

Extrinsic pathway of blood coagulation, Farber’s disease, 203t INDEX / 659
598, 599f, 601 Farnesoid X receptor, in bile acid synthesis
trans, 113–114, 192
Eye, fructose and sorbitol in, diabetic regulation, 227 transport of, carnitine in, 180–181, 181f
cataract and, 172 Farnesyl diphosphate, in cholesterol/ triacylglycerols (triglycerides) as storage

F0, in ATP synthesis, 96, 97f, 98f polyisoprenoid synthesis, form of, 114, 115f
F1, in ATP synthesis, 96, 97f, 98f 219, 220, 221f unesterified (free). See Free fatty acids
Fab region, 591, 592f Fast acetylators, 630 unsaturated. See Unsaturated fatty acids
Fabry’s disease, 203t Fast (white) twitch fibers, 574–576, 575t Fatty liver
Facilitated diffusion/transport system, 423, Fat tissue. See Adipose tissue alcoholism and, 212–214
Fatal infantile mitochondrial myopathy and of pregnancy, 188
423t, 424f, 426–427, 427, 427f renal dysfunction, oxidoreductase triacylglycerol metabolism imbalance
for bilirubin, 280 deficiency causing, 100
for glucose. See also Glucose transporters Fatigue (muscle), 136 and, 212
Fats, 111. See also Lipids Favism, 170
insulin affecting, 427 diets high in, fatty liver and, 212 Fc fragment, 591, 592f
in red cell membrane, 611 metabolism of, 122f, 123–124, 123f,
hormones in regulation of, 427 125–126, 126f receptors for, in neutrophils, 621t
“Ping-Pong” model of, 427, 427f Fatty acid-binding protein, 180, 207 Fe. See Iron
Factor I (fibrinogen), 580, 600, 600t Fatty acid chains, elongation of, 177, 177f Fed state, metabolic fuel reserves and, 232,
conversion of to fibrin, 601–602 Fatty acid elongase system, 177, 177f
Factor II (prothrombin), 600t, 601 in polyunsaturated fatty acid synthesis, 234t
coumarin drugs affecting, 487, 604 191, 191f, 192f Feedback inhibition, in allosteric regulation,
vitamin K in synthesis of, 487 Fatty acid oxidase, 181, 182f
Factor III (tissue factor), 599f, 600t, 601 Fatty acid synthase, 156t, 173 74–76, 75f, 76, 129
Factor IV. See Calcium Fatty acid synthase complex, 173–176, Feedback regulation
Factor V (proaccelerin/labile factor/accelera- 174f, 175f, 179
Fatty acid-transport protein, membrane, in allosteric regulation, 76, 129
tor globulin), 600t, 601, 602f 207 thrombin levels controlled by, 602
Factor V Leiden, 603–604 Fatty acids, 2, 111–114 Fenton reaction, 612
Factor VII (proconvertin/serum activation of, 180–181, 181f Ferric iron, 278
calcium absorption affected by, 477 in methemoglobinemia, 46
prothrombin conversion accelera- eicosanoids formed from, 190, 192, Ferrireductase, 585
tor/cothromboplastin), 599f, 193f, 194f Ferritin, 478, 585, 586
600t, 601 essential, 190, 190f, 193 protein synthesis affected by, 370
coumarin drugs affecting, 604 abnormal metabolism of, 195–196 Ferritin receptor, 586
Factor VIII (antihemophilic factor deficiency of, 191–192, 194–195 Ferrochelatase (heme synthase), 271, 272f
A/globulin), 599f, 600, 600t prostaglandin production and, 190 in porphyria, 277t
deficiency of, 604 free. See Free fatty acids Ferrous iron
Factor VIII concentrates, recombinant interconvertibility of, 231 incorporation of into protoporphyrin,
DNA technology in production in membranes, 417, 418f
of, 604 metabolism of, 123–124, 123f 271–272, 272f
Factor IX (antihemophilic factor B/Christ- nomenclature of, 111–112, 112f in oxygen transport, 40–41
mas factor/plasma thromboplas- oxidation of, 180–189. See also Fertilization, glycoproteins in, 528
tin component), 599f, 600, 600t Ketogenesis FeS. See Iron sulfur protein complex
coumarin drugs affecting, 604 acetyl-CoA release and, 123–124, Fetal hemoglobin, P50 of, 42
deficiency of, 604 123f, 181–183, 181f, 182f Fetal warfarin syndrome, 488
Factor X (Stuart-Prower factor), 599f, 600, β, 181–183, 181f, 182f α-Fetoprotein, 583t
600t ketogenesis regulation and, FFA. See Free fatty acids
activation of, 599f, 600–601 186–187, 187f, 188f FGFs. See Fibroblast growth factors
coumarin drugs affecting, 604 modified, 183,183f Fibrillin, 535, 539
Factor XI (plasma thromboplastin clinical aspects of, 187–189 Marfan syndrome caused by mutations in
antecedent), 599f, 600, 600t hypoglycemia caused by impairment
deficiency of, 601 of, 187–188 gene for, 539–540, 540f
Factor XII (Hageman factor), 599f, 600, in mitochondria, 180–181, 181f Fibrils, collagen, 535–539, 536f, 537t
600t physical/physiologic properties of, 114 Fibrin
Factor XIII (fibrin stabilizing factor/ saturated, 111, 112, 112t
fibrinoligase), 600t synthesis of, 173–179, 174f, 175f. See dissolution of by plasmin, 604–605,
Facultative heterochromatin, 316 also Lipogenesis 604f
FAD. See Flavin adenine dinucleotide carbohydrate metabolism and, 123
FADH2, fatty acid oxidation yielding, 181 citric acid cycle in, 133, 134, 135f formation of, 598–601, 599f
Familial hypertrophic cardiomyopathy, extramitochondrial, 173 thrombin in, 601–602, 603f
569–570, 570f
Fanconi’s anemia, 338 in thrombi, 598
Fibrin deposit, 598
Fibrin mesh, formation of, 598
Fibrin split products, in inflammation, 621t
Fibrin stabilizing factor (factor XIII), 600t
Fibrinogen (factor I), 580, 600, 600t

conversion of to fibrin, 601–602
Fibrinoligase (factor XIII), 600t
Fibrinolysis, 604–605
Fibrinopeptides A and B, 602, 603f

660 / INDEX Follicle-stimulating hormone (FSH), 437, Fructose
438, 439f absorption of, 475, 475f
Fibroblast growth factor receptor 3, achon- in diabetic cataract, 172
droplasia caused by mutation Footprinting, DNA, 413 glycemic index of, 474
in gene for, 551t, 554, 554f Forbes’ disease, 152t hepatic
Forensic medicine hyperlipidemia/hyperuricemia and,
Fibroblast growth factor receptors, chon- 170–171
drodysplasias caused by mutation polymerase chain reaction (PCR) in, metabolism affected by, 167, 169f
in gene for, 551t, 554, 554f 405 iron absorption affected by, 478
metabolism of, 167, 169f
Fibroblast growth factors (FGFs), 554 restriction fragment length defects in, 171–172
Fibronectin, 535, 537–538, 540, 541f polymorphisms (RFLPs) in, 411 pyranose and furanose forms of, 103f
Fibrous proteins, 30
variable numbers of tandemly repeated D-Fructose, 105t, 106f
collagen as, 38 units (VNTRs) in, 411 Fructose-1,6-bisphosphatase, 156t, 166
Figlu. See Formiminoglutamate
Final common pathway of blood Formic acid, pK/pKa value of, 12t deficiency of, 171–172
Formiminoglutamate, in histidine Fructose-2,6-bisphosphatase, 157, 158f
coagulation, 599, 601, 602f
Fingerprinting, DNA, 413 catabolism, 250, 251f in covalent catalysis, 54, 55f
FISH. See Fluorescence in situ hybridization Formyl-tetrahydrofolate, 493, 493f, 494 Fructose-1,6-bisphosphate
Fish-eye disease, 228t 43S initiation complex, in protein synthesis,
5′ cap, mRNA modification and, 355 in gluconeogenesis, 153, 154f
Flanking-sequence DNA, 397 365, 366f in glycolysis, 137, 138f
Flavin adenine dinucleotide (FAD), 86–87, 43S preinitiation complex, in protein Fructose-2,6-bisphosphate, 157–158,

290t, 489 synthesis, 365, 366f 158f
in citric acid cycle, 133 FPA/FPB. See Fibrinopeptides A and B Fructose intolerance, hereditary, 171
Flavin mononucleotide (FMN), 50, 86–87, Frameshift mutations, 363, 364f Fructose 6-phosphate

489 ABO blood group and, 619 free energy of hydrolysis of, 82t
Flavoproteins Framework regions, 592 in gluconeogenesis, 153, 154f
Free amino acids, absorption of, 477 in glycolysis, 137, 138f
electron-transferring, 87 Free energy Fructosuria, essential, 163, 171–172
as oxidases, 86–87, 88f FSF. See Fibrin stabilizing factor
Flip-flop rate, phospholipid, membrane changes in, 80–81 FSH. See Follicle-stimulating hormone
chemical reaction direction and, Fucose, in glycoproteins, 516t
asymmetry and, 420 60–61 Fucosidosis, 532–533, 533t
Flippases, membrane asymmetry and, 420 coupling and, 81–82, 81f, 82f Fucosylated oligosaccharides, selectins
Fluid mosaic model, 421f, 422 enzymes affecting, 63
Fluid-phase pinocytosis, 429–430, 429f equilibrium state and, 60–61 binding, 530
Fluidity, membrane, 422 redox potential and, 86, 87t Fucosyltransferase/fucosyl (Fuc) transferase,
Fluorescence, of porphyrins, 273–274, transition states and, 61
618
277f of hydrolysis of ATP, 82–83, 82t Fumarase (fumarate hydratase), 132f, 133
Fluorescence in situ hybridization, in gene liberation of as heat, 95 Fumarate, 132f, 133
Free fatty acids, 111, 180, 205, 206t
mapping, 406–407, 407t, in fatty liver, 212 in tyrosine catabolism, 254, 255f
635t glucose metabolism affecting, 215 in urea synthesis, 246f, 247
Fluoride, 496t insulin affecting, 215 Fumarylacetoacetate, in tyrosine catabolism,
Fluoroacetate, 130, 132f ketogenesis regulation and, 186–187,
1-Fluoro-2,4-dinitrobenzene (Sanger’s 254f, 255
reagent), for polypeptide 187f, 188f Fumarylacetoacetate hydrolase, defect at, in
sequencing, 25 lipogenesis affected by, 177–178, 177f
5-Fluorouracil, 290, 291f, 297 metabolism of, 206–207 tyrosinemia, 255
Flux-generating reaction, 129 Functional groups
FMN. See Flavin mononucleotide starvation and, 232–234, 234f, 234t
Folate. See Folic acid Free polyribosomes, protein synthesis on, amino acid chemical reactions affected
Folate trap, 492f, 494 by, 18–20
Folding 498, 506. See also
polar and charged group positioning and, Polyribosomes amino acid properties affected by, 18
6 Free radicals (reactive oxygen species). See physiologic significance of, 10–11
protein, 36–37, 37f also Antioxidants pK of, medium affecting, 13
after denaturation, 36 hydroperoxidases in protection against, Functional plasma enzymes, 57. See also
Folic acid (folate/pteroylglutamic acid), 88
482t, 492–494, 493f in kwashiorkor, 479 Enzymes
coenzymes derived from, 51 lipid peroxidation producing, 118–119, Furanose ring structures, 103f, 104
deficiency of, 250, 482t, 494 120f Fusion proteins, recombinant, in enzyme
functional, 492, 494 in oxygen toxicity, 90–91, 611–613,
forms of in diet, 492, 493f 613t study, 58, 59f
inhibitors of metabolism of, 494 xenobiotic cell injury and, 631, 631f FXR. See Farnesoid X receptor
supplemental, 494 D-Fructofuranose, 103f
Folinic acid, 493 Fructokinase, 167, 169f ∆G. See Free energy
deficiency of, 171–172 ∆G0, 60, 61, 81
D-Fructopyranose, 103f ∆GD, 61

∆GF, 61 Gastroenteropathy, protein-losing, 582 INDEX / 661
enzymes affecting, 63 Gated ion channels, 424
Gaucher’s disease, 203t disease causing, recombinant DNA
G-CSF. See Granulocyte colony-stimulating GDH. See Glutamate dehydrogenase/ technology in detection of,
factor 407–408, 408f, 409t
L-Glutamate dehydrogenase
G protein-coupled receptors (GPCRs), 458, GDP-Fuc, 516t human genome information and, 638
459, 460f GDP-Man, 516t, 517 heterogeneous nuclear RNA processing
GEFs. See Guanine nucleotide exchange
G proteins, 459, 461t in regulation of, 354
in calcium-dependent signal factors housekeeping, 376
transduction, 464f, 465 Gel electrophoresis immunoglobulin, DNA rearrangement
in cAMP-dependent signal transduction,
436, 459, 461t polyacrylamide, for protein/peptide and, 325–326, 393, 593–594
in Jak/STAT pathway, 467 purification, 24, 24f, 25f double-strand break repair and,
in respiratory burst, 623
pulsed-field, for gene isolation, 635t 337–338
GABA. See γ-Aminobutyrate Gel filtration, for protein/peptide inducible, 376
GAGs. See Glycosaminoglycans knockout, 412
Gal-Gal-Xyl-Ser trisaccharide, 518 purification, 21–22, 23f processed, 325
Gal-hydroxylysine (Hyl) linkage, 518 Gemfibrozil, 229 reporter, 385–386, 387f, 388f
Gal transferase, 618–619, 619f Gender, xenobiotic-metabolizing enzymes targeted disruption of, 412
Galactokinase, 167, 170f variations in
affected by, 630
inherited defects in, 172 Gene. See Genes; Genome methods for isolation of, 635t
Galactosamine, 169, 171f Gene array chips, protein expression and, normal, recombinant DNA techniques
D-Galactosamine (chondrosamine), 106
Galactose, 102, 167–169, 170f 28 for identification of, 407
Gene conversion, 325 size/complexity and, 397, 399t
absorption of, 475, 475f Gene disruption/knockout, targeted, 412 Genetic code, 303, 358–363, 359t
glycemic index of, 474 Gene expression features of, 358–359, 360t
in glycoproteins, 516t L-α-amino acids encoded by, 14, 15–16t
metabolism of, 167–169, 170f constitutive, 376, 378 Genetic diseases
in pyrimidine nucleotide synthesis, diagnosis of
enzyme deficiencies and, 172 enzymes in, 57
D-Galactose, 104f, 105t regulation of, 297–299 recombinant DNA technology in,
α-D-Galactose, 104f regulation of, 374–395
Galactose 1-phosphate uridyl transferase, 407–412, 408f, 409t, 410f, 411f
alternative splicing and, 354, 354f, gene therapy for, 411
167, 170f 393–394, 636 Genetic linkage. See Linkage analysis
Galactosemia, 102, 163, 172 Genetic mapping, 633, 634f. See also
Galactosidases, in glycoprotein analysis, eukaryotic transcription and, 383–387
hormones in, 458f Human Genome Project
517 negative versus positive, 374, 375t, Genetics. See also Human Genome Project
Galactoside, 106
Galactosylceramide, 116, 117f, 201, 203f 378, 380 molecular, 1
GalCer. See Galactosylceramide in prokaryotes versus eukaryotes, xenobiotic-metabolizing enzymes affected
Gallstones, 474
391–395, 392t by, 630
cholesterol, 219 regulatory protein–DNA binding Genevan system, for fatty acid
GalNAc, in glycoproteins, 515, 516t
GalNAc-Ser(Thr) linkage motifs and, 387–390, 388t, nomenclature, 111
389f, 390f, 391f Genome
in glycoproteins, 518, 519f regulatory protein DNA binding and
in glycosaminoglycans, 543 trans-activation domains and, redundancy in, 320–322
GalNAc transferase, in ABO system, 390–391, 392f removal of gene from (targeted gene
retinoic acid in, 483
618–619, 619f temporal responses and, 374–375, disruption/knockout), 412
Gamma- (γ) aminobutyrate. See 375f sequencing. See also Human Genome
Gene mapping, 319, 406–407, 407t, 633,
γ-Aminobutyrate 634f, 635t Project
Gamma- (γ) carotene, 482 Gene products, diseases associated with approaches used in, 634, 635t
Gamma-globulin, 581f deficiency of, 407t results of, 636–637, 636t, 637t
Gamma- (γ) glutamyltransferase, 630 gene therapy for, 411 working draft of, 633
Gamma- (γ) glutamyl transpeptidase Gene therapy, 411 Genomic library, 402, 413
for α1-antitrypsin deficiency emphysema, Genomic technology, 396. See also
(γ-glutamyltransferase), 589
diagnostic significance of, 57t for urea biosynthesis defects, 248 Recombinant DNA/recombinant
Gangliosides, 116 Gene transcription. See Transcription DNA technology
amino sugars in, 106, 169, 171f General acid/base catalysis, 52 Genomics, protein sequencing and, 28
sialic acids in, 110 Genes Geometric isomerism, of unsaturated fatty
synthesis of, 201–202, 203f alteration of, 323–326, 324f, 325f acids, 112–114, 114f
Gap junctions, 431 amplification of, in gene expression Geranyl diphosphate, in cholesterol
GAPs. See Guanine activating proteins regulation, 323–326, 324f, synthesis, 219, 221f
Gastric lipase, 475 325f GGT. See γ-Glutamyltransferase
Ghosts, red cell membrane analysis and, 614
Gibbs free energy/Gibbs energy. See Free
energy

662 / INDEX regulation of, 155–158, 156t, 158f Glucose 1-phosphate
allosteric modification in, 157 free energy of hydrolysis of, 82t
Gilbert syndrome, 283 covalent modification in, 157 in gluconeogenesis, 154f, 155
GK (glucokinase) gene, regulation of, 355, enzyme induction/repression in,
155–157, 156t Glucose 6-phosphate
355f fructose 2,6-bisphosphate in, free energy of hydrolysis of, 82t
Gla. See γ-Carboxyglutamate 157–158, 158f in gluconeogenesis, 153, 154f
GlcCer. See Glucosylceramide substrate (futile) cycles in, 158 in glycogen biosynthesis, 145, 146f
GlcNAc. See N-Acetylglucosamine thermodynamic barriers to glycolysis in glycolysis, 137, 138f
Glial fibrillary acid protein, 577t and, 153–155, 154f
Glibenclamide. See Glyburide Glucose-6-phosphate dehydrogenase
Globin, 278 Gluconolactone hydrolase, 163, 165f deficiency of, 163, 169–170, 613, 614f,
α-Globin gene, localization of, 407t D-Glucopyranose, 103f 619, 630t
β-Globin gene αD-Glucopyranose (α-anomer), 103f, 104 in pentose phosphate pathway, 156t,
βD-Glucopyranose (β-anomer), 103f, 104 163, 164f, 165f
localization of, 407t Glucosamine, 106f, 169, 171f
recombinant DNA technology in Glucose tolerance, 161–162, 161f
in heparin, 545 Glucose transporters, 159, 160t
detection of variations in, Glucosan (glucan), 107
407–408, 408f, 409t Glucose, 102, 102–106 in blood glucose regulation, 159, 160
Globular proteins, 30 insulin affecting, 427
β-turns in, 32, 34f absorption of, 474, 475, 475f red cell membrane, 611, 612t
β1-Globulin, 581f as amino sugar precursor, 169, 171f Glucoside, 106
transferrin as, 586 blood levels of. See Blood glucose Glucosuria, 161
γ-Globulin, 581f epimers of, 104, 104f Glucosylceramide, 116, 201, 203f
Globulins, 580 in extracellular and intracellular fluid, Glucuronate/glucuronic acid, 166–167,
Glomerular filtration, basal lamina in, 540
Glomerular membrane, laminin in, 540–542 416, 416t 168f
Glomerulonephritis, 541 furanose forms of, 103f, 104 bilirubin conjugation with, 280, 280f,
Glomerulus, renal, laminin in, 540–542 galactose conversion to, 167–169,
Glucagon, 148, 160–161 281f
in gluconeogenesis regulation, 157 170f D-Glucuronate, 105, 106f
in lipogenesis regulation, 178, 178f glycemic index of, 474 β-Glucuronidases, 281
Glucagon/insulin ratio, in ketogenesis in glycogen biosynthesis, 145, 146f Glucuronidation
regulation, 187 in glycoproteins, 516t
Glucagon-like peptide, 437 insulin secretion and, 160, 161–162 of bilirubin, 280, 280f, 281f
Glucan (glucosan), 107 interconvertibility of, 231 of xenobiotics, 628–629
Glucan transferase, in glycogenolysis, 146, isomers of, 102–104, 103f Glucuronides, 163
146f, 148f as metabolic necessity, 232 GLUT 1–4. See Glucose transporters
Glucocorticoid receptor-interacting protein metabolism of, 122–123, 122f, 123f, Glutamate
(GRIP1 coactivator), 472, 472t carboxylation of, vitamin K as cofactor
Glucocorticoid response element (GRE), 124–125, 125f, 136–140, 138f,
456, 458f, 459t 139f, 140f, 159, 159f. See also for, 487–488, 488f
Glucocorticoids, 437. See also specific type Gluconeogenesis; Glycolysis catabolism of, 249, 250f
in amino acid transport, 427 ATP generated by, 142, 143t in proline synthesis, 238, 239f
blood glucose affected by, 161 in fed state, 232 synthesis of, 237, 238f
in lipolysis, 215, 216f free fatty acids and, 215
NF-κB pathway regulated by, 468, 468f insulin affecting, 160, 161–162 transamination and, 243–244, 243f,
receptors for, 471 by pentose phosphate pathway, 123, 244f
synthesis of, 440, 441f 163–166, 164f, 165f, 167f
transport of, 454–455, 455t starvation and, 232–234, 234f, 234t, in urea biosynthesis, 243–244, 243f,
D-Glucofuranose, 103f 236 244f
Glucogenic amino acids, 231–232 permeability coefficient of, 419f
Glucokinase, 156t pyranose forms of, 103f, 104 L-Glutamate decarboxylase, 267, 268f
in blood glucose regulation, 159–160, renal threshold for, 161 Glutamate dehydrogenase/L-glutamate
160f structure of, 102, 103f
in glycogen biosynthesis, 145, 146f, 156t transport of, 159, 160t, 428, 429f, 475, dehydrogenase, 237, 238f
in glycolysis, 137, 138f, 156t 475f in nitrogen metabolism, 244–245, 244f,
Glucokinase gene, regulation of, 355, 355f insulin affecting, 427
Gluconeogenesis, 123, 125, 153–162, 154f D-Glucose, 103f, 104f, 105t 245f
blood glucose regulation and, 158–161, α-D-Glucose, 104f Glutamate-α-ketoglutarate transaminase
159f, 160f L-Glucose, 103f
citric acid cycle in, 133–134, 134f, Glucose-alanine cycle, 159 (glutamate transaminase), in urea
153–155, 154f Glucose-6-phosphatase biosynthesis, 243–244, 244f
glycolysis and, 136–140, 138f, 139f, deficiency of, 152t, 300 Glutamate-γ-semialdehyde dehydrogenase,
153–155, 154f in gluconeogenesis, 156t block at in hyperprolinemia,
in glycogenolysis, 147 250
Glutamic acid, 15t
Glutaminase, in amino acid nitrogen
catabolism, 245, 245f
Glutamine, 15t
in amino acid nitrogen catabolism, 245,
245f
catabolism of, 249, 250f
synthesis of, 237, 238f

Glutamine analogs, purine nucleotide Glycine, 15t, 264 INDEX / 663
synthesis affected by, 293 catabolism of, pyruvate formation and,
250, 252f glycogen synthase and phosphorylase in
Glutamine synthetase/synthase, 237, 238f, in collagen, 535 regulation of, 148–150,
245, 245f in heme synthesis, 264, 270–273, 273f, 150–151, 150f, 151f
274f, 275f, 276f
Glutamyl amidotransferase, PRPP, synthesis of, 238, 239f Glycolipid storage diseases, 197
regulation of, 294, 295f Glycolipids (glycosphingolipids), 111, 116,
Glycine synthase complex, 250
γ-Glutamyltransferase, 630 Glycinuria, 250 117f
γ-Glutamyl transpeptidase Glycocalyx, 110 ABO blood group and, 618
Glycochenodeoxycholic acid, synthesis of, amino sugars in, 169, 171f
(γ-glutamyltransferase), galactose in synthesis of, 167–169, 170f
diagnostic significance of, 57t 226f Glycolysis, 83, 122, 123f, 136–144, 137f
Glutaric acid, pK/pKa value of, 12t Glycocholic acid, synthesis of, 226f aerobic, 139
Glutathione Glycoconjugate (complex) carbohydrates, anaerobic, 136, 137f, 139
as antioxidant, 611–613, 613t
in conjugation of xenobiotics, glycoproteins as, 514 as muscle ATP source, 574–576, 575f,
629–630 Glycoforms, 514 575t
as defense mechanism, 629 Glycogen, 102, 107, 108f
functions of, 629–630 ATP generated by, 142, 143t
Glutathione peroxidase, 88, 166, 167f, 170, in carbohydrate metabolism, 123, 123f, clinical aspects of, 142–143
612, 613t 155 in erythrocytes, 140, 140f
Glutathione reductase, erythrocyte glucose utilization/gluconeogenesis and,
pentose phosphate pathway and, 166, carbohydrate storage and, 145, 146t
167f metabolism of, 145–152. See also 136–140, 138f, 139f, 153–155,
riboflavin status and, 490 154f. See also Gluconeogenesis
Glutathione S-transferases, 629 Glycogenesis; Glycogenolysis pathway of, 136–140, 138f, 139f, 140f
in enzyme study, 58, 59f branching in, 145, 147f pyruvate oxidation and, 134, 135f,
Glyburide (glibenclamide), 188 clinical aspects of, 151–152, 152f 140–142, 141f, 142f, 143t
Glycan intermediates, formation of during regulation of regulation of, 140
N-glycosylation, 526 enzymes in, 156t
Glycemic index, 474 cyclic AMP in, 147–150, 148f, fructose 2,6-bisphosphate in,
Glyceraldehyde (glycerose), D and L isomers 149f, 150f 157–158, 158f
of, 103f, 104f gluconeogenesis and, 140, 155–158,
Glyceraldehyde 3-phosphate glycogen synthase and 156t, 158f
in glycolysis, 137, 138f phosphorylase in, 150–151, 151f at subcellular level, 126, 127f
oxidation of, 137, 139f thermodynamic barriers to reversal of,
Glyceraldehyde 3-phosphate dehydrogenase in starvation, 234 153–155
in glycolysis, 137, 138f muscle, 145, 146t, 573, 575f Glycolytic enzymes, in muscle, 556
in red cell membranes, 615f, 616t Glycogen phosphorylase, 145–146, 146f Glycomics, 533
Glycerol, 114 pyridoxal phosphate as cofactor for, Glycophorins, 110, 518, 615–616, 615f,
in lactic acid cycle, 159 616f, 616t
permeability coefficient of, 419f 491 Glycoprotein IIb-IIIa, in platelet activation,
synthesis of, 155 regulation of, 148–150, 150–151, 150f, 607, 622t
Glycerol ether phospholipids, synthesis of, Glycoprotein glycosyltransferases, 520
199, 200f 151f Glycoproteins, 30, 109–110, 109t, 439f,
Glycerol kinase, 155, 197, 198f, 214 Glycogen storage diseases, 102, 145, 514–534, 580, 581–582. See also
Glycerol moiety, of triacylglycerols, 123 specific type and Plasma proteins
Glycerol phosphate pathway, 198f 151–152, 152t amino sugars in, 106, 169, 171f
Glycerol-3-phosphate Glycogen synthase, in glycogen metabolism, asialoglycoprotein receptor in clearance
acylglycerol biosynthesis and, 197, 197f, of, 517
198f 145, 146f, 155, 156t as blood group substances, 514, 618
free energy of hydrolysis of, 82t regulation of, 148–150, 150–151, 150f, carbohydrates in, 109t
triacylglycerol esterification and, classes of, 518, 519f
214–215, 214f 151f complex, 521, 522f
Glycerol-3-phosphate acyltransferase, 198f, Glycogen synthase a, 148–150, 150f formation of, 521, 524
199 Glycogen synthase b, 150, 150f diseases associated with abnormalities of,
Glycerol-3-phosphate dehydrogenase, 155, Glycogenesis, 124–125, 145, 146f 530, 530t, 531f, 531t, 532f, 533t
198f, 199 extracellular, absorptive pinocytosis of,
mitochondrial, 87 regulation of 430
Glycerophosphate shuttle, 99, 100f cyclic AMP in, 147–150, 148f, 149f, in fertilization, 528
Glycerophospholipids, 111 150f functions of, 514, 515t, 528–533, 529t
Glycerose (glyceraldehyde), D and L isomers enzymes in, 156t galactose in synthesis of, 167–169, 170f
of, 103f, 104f glycogen synthase and phosphorylase glycosylphosphatidylinositol-anchored,
in, 148–150, 150–151, 150f, 518, 519f, 527–528, 528t
151f high-mannose, 521, 522f
formation of, 521, 524
Glycogenin, 145, 146f
Glycogenolysis, 125, 145–147, 146f

blood glucose regulation and, 158–161,
159f, 160f

cyclic AMP-independent, 148
cyclic AMP in regulation of, 147–150,

148f, 149f, 150f
debranching enzymes in, 146–147,

148f

664 / INDEX Glycosylphosphatidylinositol-anchored GTP-γ-S, vesicle coating and, 510
(GPI-anchored/GPI-linked) Guanine, 288t
Glycoproteins (cont.) glycoproteins, 518, 519f, Guanine activating proteins, 501, 502f
hybrid, 521, 522f 527–528, 528t Guanine nucleotide exchange factors, 501,
formation of, 521
immunoglobulins as, 593 in paroxysmal nocturnal hemoglobinuria, 502f
membrane asymmetry and, 420 531, 531f Guanosine, 287f, 288t
N-linked, 518, 519f, 521–527
nucleotide sugars, 516–517, 516t Glycosyltransferases, glycoprotein, 520, base pairing of in DNA, 303, 304, 305f
O-linked, 518, 518–520, 519f, 520f, 526–527 in uric acid formation, 299, 299f
520t, 521t Guanosine diphosphate fucose (GDP-Fuc),
oligosaccharide chains of, 514 Glypiation, 528
red cell membrane, 615, 615f GM-CSF. See Granulocyte-macrophage 516t
sugars in, 515–517, 516t Guanosine diphosphate mannose
techniques for study of, 514, 515t colony-stimulating factor
asialoglycoprotein receptor in, 517 GM1 ganglioside, 116, 117f (GDP-Man), 516t, 517
glycosidases in, 517, 517t GM3 ganglioside, 116 Guanosine monophosphate. See GMP
lectins in, 517–518, 518t GMP, 288t, 297f Guanylyl cyclase, 462, 463
in zona pellucida, 528 Gyrase, bacterial, 306
cyclic, 289f, 290 Gyrate atrophy of retina, 250
Glycosaminoglycans, 109, 109f, 542, as second messenger, 290, 436, 437t,
542–547. See also specific type 457, 462–463 H bands, 556, 557f, 558f
H blood group substance, 618, 619f
amino sugars in, 106 IMP conversion to, 293, 296f H chains. See Heavy chains
deficiencies of enzymes in degradation of, feedback-regulation of, 294, 296f H1 histones, 314, 315f
H2A histones, 314, 315
545–547, 546t, 547f PRPP glutamyl amidotransferase H2B histones, 314, 315
disease associations of, 548–549 regulated by, 294 H3 histones, 314, 314–315
distributions of, 543–545, 544f, 544t H4 histones, 314, 314–315
functions of, 547–549, 548t Golgi apparatus H2S. See Hydrogen sulfide
structural differences among, 543–545, core protein synthesis in, 543 H substance, ABO blood group and, 618
glycosylation and, 509, 524–525, 525f Haber-Weiss reaction, 612
544f, 544t, 545f in membrane synthesis, 509 Hageman factor (factor XII), 599f, 600,
synthesis of, 542–543 in protein sorting, 498, 500f, 509
Glycosidases, in glycoprotein analysis, 517 in VLDL formation. 213f 600t
Glycosides, 105–106 retrograde transport from, 507 Hairpin, 306, 309f, 413
β-N-Glycosidic bond, 286, 287f Half life
Glycosphingolipids (glycolipids), 111, 116, Gout/gouty arthritis, 299
GPIIb-IIIa, in platelet activation, 607, 622t enzyme, 242
117f, 201–202, 203f GPCRs. See G protein-coupled receptors protein, 242
ABO blood group and, 618 GPI-anchored/linked glycoproteins, 518,
amino sugars in, 169, 171f plasma protein, 582
galactose in synthesis of, 167–169, 170f 519f, 527–528, 528t Halt-transfer signal, 506
in membranes, 417 in paroxysmal nocturnal hemoglobinuria, Hapten, in xenobiotic cell injury, 631,

membrane asymmetry and, 420 531, 531f 631f
Glycosuria, 161 Granulocyte-colony stimulating factor, 610 Haptoglobin, 583t, 584, 584f
N-Glycosylases, in base excision-repair, 337, Granulocyte-macrophage colony- Hartnup disease, 258, 490
HAT activity. See Histone acetyltransferase
337f stimulating factor, 610
Glycosylated hemoglobin (HbA1c), 47 Granulomatous disease, chronic, 623, 623f activity
Glycosylation Granulosa cells, hormones produced by, HbA (hemoglobin A), P50 of, 42
HbA1c (glycosylated hemoglobin), 47
of collagen, 537 442 HbF (fetal hemoglobin), P50 of, 42
congenital disorders of, 531, 531t Gratuitous inducers, 378 HbM (hemoglobin M), 46, 363, 614
in covalent modification, mass increases GRE. See Glucocorticoid response element HbS (hemoglobin S), 46, 46f, 363
GRIP1 coactivator, 472, 472t hCG. See Human chorionic gonadotropin
and, 27t Group transfer potential, 83, 83f HDL. See High-density lipoproteins
inhibitors of, 527, 527t Health, normal biochemical processes as
nucleotide sugars in, 516–517, 516t of nucleoside triphosphates, 289–290,
N-Glycosylation, 521–527, 523f, 524f, 289f, 290f, 290t basis of, 2–4, 3t
Heart
525f, 526t Group transfer reactions, 8
dolichol-P-P-oligosaccharide in, Growth factors, hematopoietic, 610 developmental defects of, 570
Growth hormone, 437, 438 metabolism in, 235t
521–524, 523f thiamin deficiency affecting, 489
in endoplasmic reticulum, 524–525, amino acid transport affected by, 427 Heart disease, coronary (ischemic). See also
localization of gene for, 407t
525f receptor for, 436 Atherosclerosis
glycan intermediates formed during, 526 GSH. See Glutathione cholesterol and, 227
in Golgi apparatus, 524–525, 525f GSLs. See Glycosphingolipids Heart failure, 556
inhibition of, 527, 527t GST (glutathione S-transferase) tag, in in thiamin deficiency, 489
regulation of, 526–527, 527t
tunicamycin affecting, 527, 527t enzyme study, 58, 59f
O-Glycosylation, 520, 521f GTP, 290

cyclic GMP formed from, 462
in phosphorylation, 85
GTPases, 459

Heat, free energy liberated as, 95 oxygen dissociation curve for, 41–42, INDEX / 665
Heat-shock proteins, as chaperones, 36–37 42f
Heavy chains Heparin, 109, 109f, 544f, 544t, 545, 545f,
in oxygen transport, 40–41 603–604
immunoglobulin, 591, 592f oxygenation of
genes producing, 593 antithrombin III activity affected by,
conformational changes and, 43, 43f, 547, 603–604
myosin, 560 44f
familial hypertrophic cardiomyopathy in basal lamina, 540
caused by mutations in gene for, apoprotein, 42 binding of, fibronectin in, 540, 541f
569–570, 570f 2,3-bisphosphoglycerate stabilizing, functions of, 547
lipoprotein and hepatic lipases affected
Heavy meromyosin, 560f, 561, 561f 45, 45f
Heinz bodies, 613 high altitude adaptation and, 46 by, 207
Helicases, DNA, 326–327, 327f, 328, 328t mutant hemoglobins and, 46 Heparin cofactor II, as thrombin inhibitor,
Helicobacter pylori, ulcers associated with, in proton transport, 44
tetrameric structure of, 42 603
474 changes in during development, Hepatic ALA synthase (ALAS1), 272
Helix
42–43, 43f in porphyria, 277t, 278
Double, of DNA structure, 7, 303, 304, Hemoglobin A (HbA), P50 of, 42 Hepatic lipase, 207
305f Hemoglobin A1c (glycosylated hemoglobin),
in chylomicron remnant uptake, 209,
recombinant DNA technology and, 47 209f
396, 397 Hemoglobin A2
Hemoglobin Bristol, 362 deficiency of, 228t
triple, of collagen structure, 38, 38f, Hemoglobin Chesapeake, 46 Hepatic portal system, 158
535–539, 536f Hemoglobin F(fetal hemoglobin), P50 of, 42
Hemoglobin Hikari, 362–363 in metabolite circulation, 124, 125f
α-Helix, 31–32, 32f, 33f Hemoglobin M, 46, 363, 614 Hepatitis, 130
amphipathic, 31–32 Hemoglobin Milwaukee, 362
in myoglobin, 40, 41f Hemoglobin S, 46, 46f, 363 in α1-antitrypsin deficiency, 590
Hemoglobin Sydney, 362 jaundice in, 284t
Helix-loop-helix motifs, 33 Hemoglobinopathies, 46, 619 Hepatocytes
Helix-turn-helix motif, 387, 388t, Hemoglobinuria, paroxysmal nocturnal, glycoprotein clearance from, asialoglyco-

389–390, 389f 432t, 528, 530t, 531, 531f protein receptor in, 517
Hemagglutinin, influenza virus, calnexin Hemolytic anemias, 136, 143, 609, 619, heme synthesis in, 272

binding to, 526 620t ALA synthase in regulation of,
Hematology, recombinant DNA glucose-6-phosphate dehydrogenase 272–273, 276f

technology affecting, 624 deficiency causing, 163, Hepatolenticular degeneration (Wilson
Hematopoietic growth factors, 610 169–170, 613, 614f, 619 disease), 432t, 587, 588–589
Heme, 40, 41f, 270 haptoglobin levels in, 584
hyperbilirubinemia/jaundice in, 282, ceruloplasmin levels in, 587
catabolism of, bilirubin produced by, 284, 284t gene mutations in, 432t, 588–589
278–280, 279f pentose phosphate pathway/glutathione Heptoses, 102, 102t
peroxidase and, 166, 167f, Hereditary elliptocytosis, 617
in proteins, 270. See also Heme proteins 169–170 Hereditary erythroblastic multinuclearity
synthesis of, 270–273, 273f, 274f, 275f, primaquine-sensitive, 613
red cell membrane abnormalities causing, with a positive acidified lysis test
276f 619 (HEMPAS), 530t, 531
disorders of (porphyrias), 274–278, Hemopexin, 583t Hereditary hemochromatosis, 586–587,
Hemophilia A, 604 587f
277f, 277t Hemophilia B, 604 Hereditary nonpolyposis colon cancer,
Heme iron, 278, 585 Hemoproteins. See Heme proteins mismatch repair genes in, 336
Hemosiderin, 586 Hereditary spherocytosis, 432t, 617, 617f
absorption of, 478, 585, 585f Hemostasis, 598–608. See also Coagulation Hermansky-Pudlak syndrome, 512t
hindered environment for, 41, 41f laboratory tests in evaluation of, 608 Hers’ disease, 152t
Heme oxygenase system, 278, 279f phases of, 598 Heterochromatin, 316
Heme proteins (hemoproteins), 270, 271t. HEMPAS. See Hereditary erythroblastic Heterogeneous nuclear RNA (hnRNA), 310
multinuclearity with a positive processing of, gene regulation and, 354
See also Hemoglobin; Myoglobin acidified lysis test Heterotrophic organisms, 82
cytochrome P450 isoforms as, 627 Henderson-Hasselbalch equation, 11 Hexapeptide, in albumin synthesis, 583
Heme synthase (ferrochelatase), 271, 272f Heparan sulfate, 538, 544f, 544t, 545, Hexokinase, 156t
in porphyria, 277t 547–548 in blood glucose regulation, 159, 160f
Hemin, 278, 279f in basal lamina, 540 in fructose metabolism, 167, 169f
Hemochromatosis, 478, 586–587, 587f clotting/thrombosis affected by, 607, in glycogen biosynthesis, 145, 156t
Hemoglobin, 40–48, 581f 607t in glycolysis, 136–137, 138f, 156t
allosteric properties of, 42–46 as flux-generating reaction, 129
β subunits of, myoglobin and, 42 regulation and, 140
bilirubin synthesis and, 278–280, 279f Hexosamines (amino sugars), 106, 106f
in carbon dioxide transport, 44, 45f glucose as precursor of, 169, 171f
extracorpuscular, haptoglobin binding of, in glycosaminoglycans, 109, 169, 171f
in glycosphingolipids, 169, 171f
583f, 584 interrelationships in metabolism of, 171f
glycosylated (HbA1c), 47
mutant, 46, 362–363
oxygen affinities (P50) and, 42–43, 43f

666 / INDEX Histidine F8 receptors for, 435– 436, 436f, 471
in oxygen binding, 40, 41f proteins as, 436
Hexose monophosphate shunt. See Pentose replacement of in hemoglobin M, 46 recognition and coupling domains on,
phosphate pathway 435–436
Histidinemia, 250 specificity/selectivity of, 435, 436f
Hexoses, 102, 102t Histone acetyltransferase activity, of
in glycoproteins, 109t signal transduction and, 456 –473
metabolism of, 163–166, 164f, 165f, coactivators, 383, 472, 473 intracellular messengers and,
167f. See also Pentose phosphate Histone chaperones, 315 457–468, 461t, 463t
pathway Histone dimer, 315 response to stimulus and, 456, 457f
clinical aspects of, 169–172 Histone octamer, 315, 315f signal generation and, 456–457, 458f,
physiologic importance of, 105, 105t Histone tetramer, 314–315, 315 459f, 459t
Histones, 314, 314–315, 315f, 315t transcription modulation and,
HFE mutations, in hemochromatosis, 468–473, 470f, 471f, 472t
586–587 acetylation and deacetylation of, gene
expression affected by, 383 stimulus recognition by, 456, 457f
HGP. See Human Genome Project storage/secretion of, 453, 454t
HhaI, 399t HIV-I, glycoproteins in attachment of, 533 synthesis of
Hierarchical shotgun sequencing, 634 HIV protease, in acid-base catalysis, 52, 53f
High altitude, adaptation to, 46 HMG-CoA. See 3-Hydroxy-3-methyl- chemical diversity of, 438, 439f
High-density lipoproteins, 205, 206t cholesterol in, 438, 438–445, 439t,
glutaryl-CoA
apolipoproteins of, 205–206, 206t HMM. See Heavy meromyosin 440f
atherosclerosis and, 210–211, 227 hMSH1/hMSH2, in colon cancer, 336 peptide precursors and, 449–453
metabolism of, 209–211, 211f HNCC. See Hereditary nonpolyposis colon specialization of, 437
ratio of to low-density lipoproteins, 227 tyrosine in, 438, 439–449, 439t
receptor for, 210, 211f cancer target cells for, 434–435, 435t
High-density microarray technology, 412 hnRNA. See Heterogeneous nuclear RNA transport of, 454–455, 454t, 455t
High-energy phosphates, 83. See also ATP Holocarboxylase synthetase, biotin as vitamin D as, 484–486
in energy capture and transfer, 82–83, Housekeeping genes, 376
coenzyme of, 494 Hp. See Haptoglobin
82f, 82t, 83f Homeostasis HpaI, 399t
as “energy currency” of cell, 83–85, 84f, HPETE. See Hydroperoxides
blood in maintenance of, 580 HPLC. See High-performance liquid
85f hormone signal transduction in
symbol designating, 83 chromatography
transport of, creatine phosphate shuttle regulation of, 456, 457f HREs. See Hormone response elements
Homocarnosine, 264, 265f HRPT. See Hypoxanthine-guanine
in, 100, 101f Homocarnosinosis, 264
High-mannose oligosaccharides, 521, Homocysteine phosphoribosyl transferase
hsp60/hsp70, as chaperones, 36–37
522f in cysteine and homoserine synthesis, 5HT (5-hydroxytryptamine). See Serotonin
formation of, 521, 524 238–239, 239f Human chorionic gonadotropin (hCG), 438
High-molecular-weight kininogen, 599f, 600 Human Genome Project, 3–4, 633–641
High-performance liquid chromatography, functional folate deficiency and, 494
Homocystinurias, 250 approaches used in elucidation of, 634,
reversed phase, for protein/ 635t
peptide purification, 23–24 vitamin B12 deficiency/functional folate
Hill coefficient, 67 deficiency and, 492f, 494 future work and, 637
Hill equation, 66–67, 67f goals of, 633–635
Hindered environment, for heme iron, 41, Homodimers, 34 implications of, 637–638
41f Homogentisate, in tyrosine catabolism, major findings of, 636–637, 636t, 637t
HindIII, 399t protein sequencing and, 28
Hinge region 254f, 255 Human immunodeficiency virus (HIV-I),
immunoglobulin, 591, 592f Homogentisate dioxygenase/oxidase, 89
nuclear receptor protein, 460 glycoproteins in attachment of,
Hippuric acid/hippurate, synthesis of, 264, deficiency of, in alkaptonuria, 255 533
265f Homology Hunter syndrome, 546t
Histamine, 621t Hurler syndrome, 546t
formation of, 265 conserved residues and, 54, 55t Hurler-Scheie syndrome, 546t
Histidase, impaired, 250 in protein classification, 30 Hyaluronic acid, 109, 109f, 543, 544f, 544t
Histidine, 16t, 265, 265f Homopolymer tailing, 399 disease associations and, 548
β-alanyl dipeptides and, 264, 265f Homoserine, synthesis of, 239, 239f functions of, 547
catabolism of, 250, 251f Hormone-dependent cancer, vitamin B6 Hyaluronidase, 547
conserved residues and, 55t Hybrid glycoproteins, 521, 522f
decarboxylation of, 265 deficiency and, 491 formation of, 521
in oxygen binding, 40, 41f Hormone response elements, 349, 386, Hybrid mapping, radiation, 635t
requirements for, 480 Hybridization, 397, 403–404, 413
Histidine 57, in covalent catalysis, 53–54, 388f, 456–457, 459t, 469, 470f in situ, in gene mapping, 406–407, 407t,
54f Hormone-sensitive lipase, 214–215, 214f 635t
Histidine E7, in oxygen binding,
40, 41f insulin affecting, 215
Hormones. See also specific type

in blood glucose regulation, 159
classification of, 436–437, 437t
facilitated diffusion regulated by, 427
glycoproteins as, 514
lipid metabolism regulated by, 215–217,

216f
in metabolic control, 128f, 129

Hybridomas, 595–596, 596f 17α-Hydroxylase, in steroid synthesis, 440, INDEX / 667
Hydrocortisone. See Cortisol 441f, 442, 443f
Hydrogen bonds, 5, 6f Hyperglycemia. See also Diabetes mellitus
18-Hydroxylase, in steroid synthesis, 440, glucagon causing, 161
in DNA, 303, 304, 305f 441f insulin release in response to, 466f
Hydrogen ion concentration. See also pH
21-Hydroxylase, in steroid synthesis, 440, Hyperhomocysteinemia, folic acid supple-
enzyme-catalyzed reaction rate affected 441f ments in prevention of, 494
by, 64, 64f
27-Hydroxylase, sterol, 226 Hyperhydroxyprolinemia, 255
Hydrogen peroxide Hydroxylase cycle, 89, 90f Hyperkalemic periodic paralysis, 569t
glutathione in decomposition of, 629 Hydroxylases, 89–90 Hyperlacticacidemia, 212
as hydroperoxidase substrate, 88–89 Hyperlipidemia, 170–171, 490
production of in respiratory burst, 622 in steroid synthesis, 438, 440, 441f Hyperlipoproteinemias, 205, 228t, 229
Hydroxylation
Hydrogen sulfide, respiratory chain affected familial, 228t
by, 95, 96f in collagen processing, 537 Hyperlysinemia, periodic, 258
in covalent modification, mass increases Hypermetabolism, 136, 479
Hydrolases, 50 Hyperornithinemia-hyperammonemia
cholesteryl ester, 223 and, 27t
fumarylacetoacetate, defect at, in of xenobiotics, 626, 626–628, 629t syndrome, 250
tyrosinemia, 255 Hydroxylysine, synthesis of, 240 Hyperoxaluria, primary, 250
gluconolactone, 163, 165f 5-Hydroxymethylcytosine, 287, 289f Hyperparathyroidism, bone and cartilage
lysosomal, deficiencies of, 532–533, 533t 3-Hydroxy-3-methylglutaryl-CoA
affected in, 551t
Hydrolysis (hydrolytic reactions), 7–8. See (HMG-CoA) Hyperphenylalaninemias, 255
also specific reaction in ketogenesis, 184–185, 185f Hyperprolinemias, types I and II, 249–250
in mevalonate synthesis, 219, 220f Hypersensitive sites, chromatin, 316
free energy of, 82–83, 82t 3-Hydroxy-3-methylglutaryl-CoA Hypersplenism, in hemolytic anemia, 619
in glycogenolysis, 146, 146f, 148f Hypertension, hyperhomocysteinemia and,
of triacylglycerols, 197 (HMG-CoA) lyase
Hydropathy plot, 419 deficiency of, 188 folic acid supplements in
Hydroperoxidases, 86, 88–89 in ketogenesis, 185, 185f prevention of, 494
Hydroperoxides, formation of, 194, 195f 3-Hydroxy-3-methylglutaryl-CoA Hyperthermia, malignant, 556, 564–565,
Hydrophilic compounds, hydroxylation 565f, 569t
(HMG-CoA) reductase Hypertriacylglycerolemia
producing, 627 cholesterol synthesis controlled by, 220, in diabetes mellitus, 205
Hydrophilic portion of lipid molecule, 119, familial, 228t
223f Hypertrophic cardiomyopathy, familial,
120f in mevalonate synthesis, 219, 220f 569–570, 570f
Hydrophobic effect, in lipid bilayer self- 3-Hydroxy-3-methylglutaryl-CoA Hyperuricemia, 170–171, 300
Hypervariable regions, 591–592, 594f
assembly, 418 (HMG-CoA) synthase Hypoglycemia, 153
Hydrophobic interaction chromatography, in ketogenesis, 185, 185f fatty acid oxidation and, 180, 187–188
in mevalonate synthesis, 219, 220f fructose-induced, 171–172
for protein/peptide purification, p-Hydroxyphenylpyruvate, in tyrosine insulin excess causing, 162
23 during pregnancy and in neonate, 161
Hydrophobic interactions, 6–7 catabolism, 254f, 255 Hypoglycin, 180, 188
Hydrophobic portion of lipid molecule, 17-Hydroxypregnenolone, 440, 441f Hypokalemic periodic paralysis, 569t
119, 120f 17-Hydroxyprogesterone, 440, 441f Hypolipidemic drugs, 229
Hydrostatic pressure, 580 Hydroxyproline Hypolipoproteinemia, 205, 228t, 229
L(+)-3-Hydroxyacyl-CoA dehydrogenase, Hypouricemia, 300
181, 182f synthesis of, 240, 240f, 535–537 Hypoxanthine, 289
3-Hydroxyanthranilate dioxygenase/ tropoelastin hydroxylation and, 539 Hypoxanthine-guanine phosphoribosyl
oxygenase, 89 4-Hydroxyproline, catabolism of, 253f, transferase (HRPT)
Hydroxyapatite, 549 defect of in Lesch-Nyhan syndrome, 300
D(–)-3-Hydroxybutyrate (β-hydroxy- 255 localization of gene for, 407t
butyrate), 183–184, 184f 4-Hydroxyproline dehydrogenase, defect in, Hypoxia, lactate production and, 136, 137f,
D(–)-3-Hydroxybutyrate dehydrogenase, 139–140
184, 184f in hyperhydroxyprolinemia,
24-Hydroxycalcidiol (24,25-dihydroxyvita- 255 I. See Iodine/iodide
min D3), in vitamin D 15-Hydroxyprostaglandin dehydrogenase, I bands, 556, 557f, 558f
metabolism, 484, 485f 194 I-cell disease, 431, 432t, 512t, 524, 530t,
25-Hydroxycholecalciferol (calcidiol), in 3β-Hydroxysteroid dehydrogenase, 438,
vitamin D metabolism, 484, 485f 441f, 442, 443f 531–532, 532t, 546–547, 546t
4-Hydroxydicoumarin (dicumarol), 486 17β-Hydroxysteroid dehydrogenase, 442, Ibuprofen, cyclooxygenases affected by, 193
Hydroxylamine, for polypeptide cleavage, 443f ICAM-1, 529, 529t
26t 5-Hydroxytryptamine. See Serotonin ICAM-2, 529, 529t
7α-Hydroxylase, bile acid synthesis Hyperalphalipoproteinemia, familial, 228t ICF. See Intracellular fluid
regulated by, 226, 226f, 227 Hyperammonemia, types 1 and 2, 247
11β-Hydroxylase, in steroid synthesis, 440, Hyperargininemia, 248
441f Hyperbilirubinemia, 281–284, 284t
Hypercholesterolemia, 205
familial, 1, 228t, 432t
LDL receptor deficiency in, 209, 432t
Hyperchromicity of denaturation, 304–305

668 / INDEX in gluconeogenesis regulation, Insert/insertions, DNA, 413
155–157 recombinant DNA technology in
Icterus (jaundice), 270, 281–284, 284t detection of, 409
IDDM. See Insulin-dependent diabetes gratuitous, 378
in regulation of gene expression, 376 Inside-outside asymmetry, membrane,
mellitus Inducible gene, 376 419–420
Idiotypes, 594 Infantile Refsum disease, 188, 503, 503t
IDL. See Intermediate-density lipoproteins Infection Insulators, 387
L-Iduronate, 105, 106f glycoprotein hydrolase deficiencies and, nonpolar lipids as, 111
IEF. See Isoelectric focusing
IgA, 591, 594t, 595f 533 Insulin, 107–109, 438, 449, 450f
IgD, 591, 594t neutrophils in, 620, 621t adipose tissue metabolism affected by,
IgE, 591, 594t protein loss and, 480 216–217
IGF-I. See Insulin-like growth factor-I respiratory burst in, 622–623 in blood glucose regulation, 160–162
IgG, 591, 592f, 594t Inflammation, 190 deficiency of, 161. See also Diabetes
acute phase proteins in, 583, 583t mellitus
deficiency of, 595 complement in, 596 free fatty acids affected by, 215
hypervariable regions of, 591–592, neutrophils in, 620, 621t gene for, localization of, 407t
glucagon opposing actions of, 160–161
594f integrins and, 529t, 620–621, 622t in glucose transport, 427
IgM, 591, 594t, 595f selectins and, 528–529, 529t, 530f in glycolysis, 137, 155–157
Immune response, class/isotype switching NF-κB in, 468 initiation of protein synthesis affected by,
prostaglandins in, 190 367, 367f
and, 594 selectins in, 528–530, 529f, 529t, 530f in lipogenesis regulation, 178–179
Immunoglobulin genes, 593 Influenza virus in lipolysis regulation, 178–179, 215,
hemagglutinin in, calnexin binding to, 216f
DNA rearrangement and, 325–326, 393, phosphorylase b affected by, 148
593–594 526 receptor for, 436, 465, 466f
neuraminidase in, 533 signal transmission by, 465–467, 466f
double-strand break repair and, Information pathway, 457, 459f storage/secretion of, 453, 454t
337–338 Inhibition synthesis of, 449, 450f
competitive versus noncompetitive,
Immunoglobulin heavy chain binding Insulin-dependent diabetes mellitus
protein, 508 67–69, 67f, 68f, 69f (IDDM/type 1), 161–162. See
feedback, in allosteric regulation, 74–76, also Diabetes mellitus
Immunoglobulin heavy chains, 591, 592f
genes producing, 593 75f Insulin/glucagon ratio, in ketogenesis
irreversible, 69 regulation, 187
Immunoglobulin light chains, 591, 592f Inhibitor-1, 148, 149f, 151, 151f
in amyloidosis, 590 Initial velocity, 64 Insulin-like growth factor I, receptor for, 436
genes producing, 593 inhibitors affecting, 68, 68f, 69f Insulin resistance, 611
DNA rearrangement and, 325–326, Initiation Integral proteins, 30, 420, 421f
393, 593–594 in DNA synthesis, 328–330, 329f, 330f,
as receptors, 431
Immunoglobulins, 583t, 591–597, 593t. 331f red cell membrane, 615–616, 615f, 616f,
See also specific type under Ig in protein synthesis, 365–367, 366f
in RNA synthesis, 342, 342f, 343–344 616t
class switching and, 594 Initiation complexes, in protein synthesis, Integration, chromosomal, 324, 324f
classes of, 591, 593t, 594t Integrins, neutrophil interactions and, 529t,
diseases caused by over- and 365, 366f, 367
Initiator sequence, 346–348, 347f 620–621, 622t
underproduction of, 594–595 Inner mitochondrial membrane, 92, 93f Intercellular junctions, 431
functions of, 593, 594t Intermediate-density lipoproteins, 206t
genes for. See Immunoglobulin genes impermeability of, exchange transporters Intermediate filaments, 577–578, 577t
hybridomas as sources of, 595–596, 596f and, 98–100, 98f, 99f Intermembrane space, proteins in, 501
structure of, 591, 592, 592f, 594f, 595f Intermittent branched-chain ketonuria, 259
IMP (inosine monophosphate) protein insertion in, 501 Internal presequences, 501
conversion of to AMP and GMP, 293, Inorganic pyrophosphatase, in fatty acid Internal ribosomal entry site, 371, 371f
Interphase chromosomes, chromatin fibers
296f activation, 85
feedback regulation of, 294, 296f Inosine monophosphate (IMP) in, 316
synthesis of, 293–294, 295f, 296f, 297f Intervening sequences. See Introns
Importins, 501, 502f conversion of to AMP and GMP, 293, Intestinal bacteria, in bilirubin conjugation,
In situ hybridization/fluorescence in situ 296f
281
hybridization, in gene mapping, feedback-regulation of, 294, 296f Intracellular environment, membranes in
406–407, 407t, 635t synthesis of, 293–294, 295f, 296f, 297f
Inactive chromatin, 316–318, 383 Inositol hexaphosphate (phytic acid), calcium maintenance of, 415–416, 416t
Inborn errors of metabolism, 1, 249, 545 Intracellular fluid (ICF), 415, 416, 416t
Inclusion cell (I-cell) disease, 431, 432t, absorption affected by, 477 Intracellular membranes, 415
512t, 524, 530t, 531–532, 532t Inositol trisphosphate, 464–465, 464f, 465f Intracellular messengers, 457–468, 461t,
Indole, permeability coefficient of, 419f
Indomethacin, cyclooxygenases affected by, in platelet activation, 606, 606f, 607 463t. See also specific type and
193 in respiratory burst, 623 Second messengers
Induced fit model, 52, 53f Inotropic effects, 566
Inducers Inr. See Initiator sequence
enzyme synthesis affected by, 74

Intracellular signals, 457–458 metabolism of, 585, 585f INDEX / 669
Intracellular traffic, 498–513. See also disorders of, 586, 587t
J chain, 595f
Protein sorting nonheme, 92, 95f, 585 Jackson-Weiss syndrome, 551t
disorders due to mutations in genes transferrin in transport of, 584–586, JAK kinases, 436, 467, 467f
Jak-STAT pathway, 436, 467, 467f
encoding, 512t, 513 585f, 585t Jamaican vomiting sickness, 188
Intrinsic factor, 477, 491–492 Iron-binding capacity, total, 586 Jaundice (icterus), 270, 281–284, 284t
Iron deficiency/iron deficiency anemia, 478, Joining region, gene for, 593
in pernicious anemia, 492
Intrinsic pathway of blood coagulation, 497, 586 DNA rearrangement and, 393, 593–594
Iron porphyrins, 270 “Jumping DNA,” 325
598, 599f, 600–601 Iron regulatory protein, 585 Junctional diversity, 593–594
Introns (intervening sequences), 319, Iron response elements, 586 Juxtaglomerular cells, in renin-angiotensin
Iron-sulfur protein complex, 92, 95f
352–354, 353f, 358, 413 Irreversible covalent modifications, 76–77, system, 451
in recombinant DNA technology, 397,
77f K. See Dissociation constant
398f Irreversible inhibition, enzyme, 69 K. See Potassium
removal of from primary transcript, IRS 1–4, in insulin signal transmission, k. See Rate constant
Kd. See Dissociation constant
352–354, 353f 465, 466f kdeg. See Rate of degradation
Inulin, glomerular membrane permeability Ischemia, 136, 431 Keq. See Equilibrium constant
Islets of Langerhans, insulin produced by, Km. See Michaelis constant
to, 540 ks. See Rate of synthesis
“Invert sugar,” 107 160 Kw. See Ion product
Iodine/iodide, 496t Isocitrate dehydrogenase, 130–131, 132f Kappa (κ) chains, 591
Kartagener syndrome, 577
deficiency of, 447–449 in NADPH production, 176, 176f Karyotype, 320f
in thyroid hormone synthesis, 447, 448f, Isoelectric focusing, for protein/peptide Kayser-Fleischer ring, 588
KDEL-containing proteins, 506–507,
449 purification, 24, 25f
5-Iodo-2′-deoxyuridine, 291f Isoelectric pH (pI), amino acid net charge 508t
Iodopsin, 483 Keratan sulfates, 544f, 544t, 545
o-Iodosobenzene, for polypeptide cleavage, and, 17
Isoenzymes. See Isozymes functions of, 547
26t Isoleucine, 15t Keratins, 577t, 578
Iodothyronyl residues, 447. See also Kernicterus, 282, 283
catabolism of, 259, 260f, 261f α-Keto acid decarboxylase, defect/absence
Thyroxine; Triiodothyronine interconversion of, 240
5-Iodouracil, 290 requirements for, 480 of, in maple syrup urine disease
Ion channels, 415, 423–424, 425f, 426t, ∆5,4-Isomerase, 438, 441f, 442, 443f (branched-chain ketonuria), 259
Isomerases, 50 α-Keto acid dehydrogenase,
568t in steroid synthesis, 438, 441f, 442, branched-chain, 259
in cardiac muscle, 566–567, 568, 568t thiamin diphosphate as coenzyme for,
diseases associated with disorders of, 568, 443f 488–489
Isomerism α-Keto acids
569t amino acids in diet replaced by, 240
Ion exchange chromatography, for protein/ geometric, of unsaturated fatty acids, oxidative carboxylation of, 259, 260f,
112–114, 114f 261f, 262f
peptide purification, 22–23 Ketoacidosis, 180, 188–189
Ion product, 8–9 of steroids, 117, 118f 3-Ketoacyl-CoA thiolase deficiency, 188
Ion transport, in mitochondria, 99 of sugars, 102–104, 103f 3-Ketoacyl synthase, 173, 175f
Ionizing radiation, nucleotide excision- Isoniazid, acetylation of, 630 Ketogenesis, 125–126, 126f, 183–187
Isopentenyl diphosphate, in cholesterol high rates of fatty acid oxidation and,
repair of DNA damage caused 183–186, 184f
by, 337 synthesis, 219, 221f HMG-CoA in, 184–185, 185f
Ionophores, 99, 424 Isoprene units, polyprenoids synthesized regulation of, 186–187, 187f, 188f
IP3. See Inositol trisphosphate Ketogenic amino acids, 232
IPTG. See Isopropylthiogalactoside from, 118, 119f α-Ketoglutarate, 131
IREG1. See Iron regulatory protein Isoprenoids, synthesis of, in cholesterol in amino acid carbon skeleton
IRES. See Internal ribosomal entry site catabolism, 249, 250, 250f,
Iron, 496t synthesis, 219, 221f, 222f 251f
absorption of, 478, 584–586, 585f, Isopropylthiogalactoside, 378 in glutamate synthesis, 237, 238f, 243,
585t Isoprostanes (prostanoids), 112, 119 243f, 244f
in hemochromatosis, 478 transporter systems for, 99
vitamin C and ethanol affecting, 478, cyclooxygenase pathway in synthesis of, in urea synthesis, 244, 244f
496 192, 192–194, 193f, 194f
deficiency of, 497
distribution of, 585t Isothermic systems, biologic systems as,
ferrous, in oxygen transport, 40–41 80
heme, 278, 585
absorption of, 478, 585, 585f Isotopes. See also specific type
hindered environment for, 41, 41f in plasma protein analysis, 581
in methemoglobinemia, 46
incorporation of into protoporphyrin, Isotype (class) switching, 594
271–272, 272f Isotypes, 594
Isovaleric acidemia, 259, 259–262
Isovaleryl-CoA dehydrogenase, in isovaleric

acidemia, 259–262
Isozymes, 54–55

670 / INDEX Kynurenine-anthranilate pathway, for Lauric acid, 112t
tryptophan catabolism, 257f, 258 Laws of thermodynamics, 80–81
α-Ketoglutarate dehydrogenase complex,
131, 132f Kynurenine formylase, 257f, 258 hydrophobic interactions and, 7
LBD. See Ligand-binding domain
regulation of, 135 L-α-amino acids, 14. See also Amino acids LCAT. See Lecithin:cholesterol
thiamin diphosphate as coenzyme for, genetic code specifying, 14, 15–16t
in proteins, 14 acyltransferase
488–489 LCRs. See Locus control regions
Ketone bodies, 124, 125–126, 126f, 180, L chains. See Light chains LDH. See Lactate dehydrogenase isozymes
L-Dopa, 446, 447f LDL. See Low-density lipoproteins
183–184, 184f L isomerism, 102–104, 103f LDL:HDL cholesterol ratio, 227
free fatty acids as precursors of, 186 L-selectin, 529f, 529t Lead poisoning, ALA dehydratase inhibition
as fuel for extrahepatic tissues, 185–186, L-type calcium channel, 567
Labile factor (factor V), 600t, 601, 602f and, 270, 278
186f lacA gene, 376, 376f, 377f, 378 Leader sequence. See Signal peptide
in starvation, 232–234, 234f, 234t lacI gene, 377, 377f, 378 Leading (forward) strand, in DNA
Ketonemia, 186, 188 lac operon, 375, 376–378, 376f, 377f
Ketonuria, 188 lac repressor, 377, 377f replication, 327f, 328, 330
branched chain (maple syrup urine lacY gene, 376, 376f, 377f, 378 Lecithin:cholesterol acyltransferase (LCAT),
lacZ gene, 376, 376f, 377f, 378
disease), 259 Lactase, 475 200–201, 209–210, 211f, 223,
Ketoses (sugars), 102, 102t 224
Ketosis, 180, 186, 188 deficiency of (lactose/milk intolerance), familial deficiency of, 228t
102, 474, 475 Lecithins (phosphatidylcholines), 114–115,
in cattle 115f
fatty liver and, 212 Lactate in cytochrome P450 system, 617
lactation and, 188 anaerobic glycolysis and, 136, 137f, membrane asymmetry and, 420
139–140 synthesis of, 197, 197f, 198f
in diabetes mellitus, 188 hypoxia and, 137f, 139–140 Lectins, 110, 517–518, 518t
ketoacidosis caused by, 188–189 in glycoprotein analysis, 515t, 517–518,
nonpathologic, 188–189 Lactate dehydrogenase, in anaerobic 518t
in starvation, 188 glycolysis, 139 Leiden factor V, 603
Kidney Lens of eye, fructose and sorbitol in,
glycogenolysis in, 147 Lactate dehydrogenase isozymes, 57, 139 diabetic cataract and, 172
metabolism in, 235t diagnostic significance of, 57, 57t, 58f Leptin, 215–216
in renin-angiotensin system, 451 Lesch-Nyhan syndrome, 300
vitamin D3 synthesis in, 445, 446f, 484 Lactic acid, pK/pKa value of, 12t Leucine, 15t
Kinases, protein. See Protein kinases Lactic acid cycle, 159, 159f catabolism of, 259, 260f, 261f
Kinesin, 577 Lactic acidosis, 92, 136 interconversion of, 240
Kinetic (collision) theory, 61 requirements for, 480
Kinetics (enzyme), 60–71. See also Catalysis with mitochondrial encephalopathy and Leucine aminomutase, 492
activation energy affecting, 61, 63 stroke-like episodes (MELAS), Leucine zipper motif, 387–388, 388t, 390,
balanced equations and, 60 100–101 391f
competitive versus noncompetitive inhi- Leucovorin, 493
pyruvate metabolism and, 142–143 Leukocyte adhesion deficiency
bition and, 67–69, 67f, 68f, 69f thiamin deficiency and, 489 type I, 621
factors affecting reaction rate and, type II, 530t, 531
Lactoferrin, 621t Leukocytes, 620–624
61–63, 62f, 63–64, 64f Lactogenic hormone. See Prolactin growth factors regulating production of,
free energy changes affecting, 60–61 Lactose, 106–107, 107f, 107t 610
initial velocity and, 64 recombinant DNA technology in study
multisubstrate enzymes and, 69–70, 69f, galactose in synthesis of, 167–169, 170f of, 624
metabolism of, operon hypothesis and, Leukodystrophy, metachromatic, 203t
70f Leukotriene A4, 114f
saturation, 64f, 66 376–378, 376f, 377f Leukotrienes, 112, 114f, 190, 192
Lactose (milk) intolerance, 102, 474, 475 clinical significance of, 196
sigmoid (Hill equation), 66–67, 67f Lactose synthase, 167, 170f lipoxygenase pathway in formation of,
substrate concentration and, 64, 64f, 65f Lagging (retrograde) strand, in DNA 192, 193f, 194, 195f
LFA-1, 529, 529t, 620, 622t
models of effects of, 65–67, 66f, 67f replication, 327f, 328, 330–331 LH. See Luteinizing hormone
transition states and, 61 Lambda (λ) chains, 591 Library, 402, 413
Kinetochore, 318 Lambda (λ) phage, 378–383, 379f, 380f, Lifestyle changes, cholesterol levels affected
Kininogen, high-molecular-weight, 599f, by, 227–228
381f, 382f Ligand-binding domain, 470
600 Lambda repressor (cI) protein/gene, Ligand-gated channels, 424, 568t
Kinky hair disease (Menkes disease), 588
Knockout genes, 412 379–383, 380f, 381f, 382f
Korsakoff’s psychosis, 489 Laminin, 535, 540–542, 541f
Kozak consensus sequences, 365 Lamins, 577t, 578
Krabbe’s disease, 203t Langerhans, islets of, insulin produced by,
Krebs cycle. See Citric acid cycle
Ku, in double-strand break repair, 338, 160
Lanosterol, in cholesterol synthesis, 219,
338f
Kwashiorkor, 237, 478, 478–479 220, 222f
Kynureinase, 257f, 258 Latch state, 571

Ligand-receptor complex, in signal disorders associated with abnormalities INDEX / 671
generation, 456–457 of, 431
remnant, 206t, 208, 209f
Ligases, 50 fatty acids, 111–114 liver uptake of, 208–209
DNA, 328t, 330, 332, 332f glycolipids, 111, 116, 117f
interconvertibility of, 231 Liposomes, 421
Ligation, 413 in membranes, 416–418 amphipathic lipids forming, 119–121,
in RNA processing, 352 120f
ratio of to protein, 416, 416f artificial membranes and, 421
Light, in active transport, 427 metabolism of, 122f, 123–124, 123f,
Light chains Lipotropic factor, 212
125–126, 126f. See also Lipolysis β-Lipotropin, 453, 453f
immunoglobulin, 591, 592f in fed state, 232 Lipoxins, 112, 114f, 190, 192
in amyloidosis, 590 in liver, 211–212, 213f
genes producing, 593 neutral, 111 clinical significance of, 196
DNA rearrangement and, 325–326, peroxidation of, 118–119, 120f lipoxygenase pathway in formation of,
393, 593–594 phospholipids, 111, 114–116, 115f
precursor, 111 192, 193f, 194, 195f
myosin, 560 simple, 111 Lipoxygenase, 119, 194, 195f
in smooth muscle contraction, 570 steroids, 117–118, 117f, 118f, 119f
transport and storage of, 205–218 reactive species produced by, 119
Light meromyosin, 560–561, 560f adipose tissue and, 214–215, 214f 5-Lipoxygenase, 194, 195f
Limit dextrinosis, 152t brown adipose tissue and, 217, 217f Lipoxygenase pathway, 192, 193f, 194,
Lines, definition of, 413 clinical aspects of, 212–214
LINEs. See Long interspersed repeat fatty acid deficiency and, 194–195 195f
as lipoproteins, 205–206, 206t, 207f Liquid chromatography, high-performance
sequences liver in, 211–212, 213f
Lineweaver-Burk plot triacylglycerols (triglycerides), 114, 115f reversed-phase, for peptide
turnover of, membranes and, 511–512 separation, 23–24
inhibitor evaluation and, 68, 68f, 69f Lipogenesis, 125, 173–177, 174f, 175f Lithium, 496t
Km and Vmax estimated from, 66, 66f acetyl-CoA for, 176–177 Lithocholic acid, synthesis of, 226f
Lingual lipase, 475 fatty acid synthase complex in, 173–176, Liver
Link trisaccharide, in glycosaminoglycan angiotensinogen made in, 451
174f, 175f bilirubin uptake by, 280–281, 280f,
synthesis, 543 malonyl-CoA production in, 173, 174f 281f, 282f
Linkage analysis, 635t NADPH for, 175f, 176, 176f cirrhosis of, 130, 212
regulation of, 178–179, 178f in α1-antitrypsin deficiency, 590
in glycoprotein study, 515t cytochrome P450 isoforms in, 627
Linoleic acid/linoleate, 113t, 190, 190f, enzymes in, 156t, 173, 174f, 178, disorders of, in α1-antitrypsin deficiency,
178f 589–590, 590f
192 fatty
in essential fatty acid deficiency, 191 nutritional state in, 177–178 alcoholism and, 212–214
synthesis of, 191f Lipolysis, 125, 126f, 216–217, 216f. See of pregnancy, 188
α-Linolenic acid/α-linolenate, 113t, 190, triacylglycerol metabolism imbalance
also Lipids, metabolism of and, 212
190f, 192 hormone-sensitive lipase in, 214–215, fructose overload and, 170–171
in essential fatty acid deficiency, 191 glycogen in, 145, 146t
synthesis of, 191, 191f 214f heme synthesis in, 272
γ-Linolenic acid/γ-linolenate, 113t hormones affecting, 215–216, 216f ALA synthase in regulation of,
in essential fatty acid deficiency, 191 insulin affecting, 178–179 272–273, 276f
in polyunsaturated fatty acid synthesis, triacylglycerol, 197 ketone bodies produced by, 183–184,
Lipophilic compounds, cytochrome P450 184f, 186
191, 192f metabolism in, 124–125, 125f, 126f,
Lipases isoforms in hydroxylation of, 627 130, 235t
Lipoprotein lipase, 125, 126f, 207–208, fatty acid oxidation, ketogenesis and,
diagnostic significance of, 57t 183–186, 184f
in digestion, 475, 476f 209f, 210f fructose, 167, 169f
in triacylglycerol metabolism, 197, familial deficiency of, 228t glucose, 154f, 159, 159–160,
involvement in remnant uptake, 208, 159f
214–215, 214f, 475, 476f fructose 2,6-bisphosphate in
Lipid bilayer, 418–419, 418f, 419f 209f regulation of, 157–158, 158f
α1-Lipoprotein, 581f glycogen, 145–147, 145, 146f, 148
membrane proteins and, 419 β1-Lipoprotein, 581f lipid, 211–212, 213f
Lipid core, of lipoprotein, 205 Lipoprotein(a) excess, familial, 228t plasma protein synthesis in, 125, 581
Lipid rafts, 422 Lipoproteins, 30, 111, 125, 205–206, 206t, vitamin D3 synthesis in, 445, 446f, 484,
Lipid storage disorders (lipidoses), 485f
207f, 580, 583t. See also specific Liver phosphorylase, 147
202–203, 203t type deficiency of, 152t
Lipids, 111–121. See also specific type carbohydrates in, 110 LMM. See Light meromyosin
in cholesterol transport, 223–224, 225f Lock and key model, 52
amphipathic, 119–121, 120f classification of, 205, 206t
asymmetry of, membrane assembly and, deficiency of, fatty liver and, 212
disorders of, 228t, 229
511, 512f
classification of, 111
complex, 111
in cytochrome P450 system, 627
derived, 111
digestion and absorption of, 475–477,

476f

672 / INDEX Lysosomal enzymes, 623 D-Mannose, 104f, 105t
in I-cell disease, 431, 432t, 531–532, α-D-Mannose, 104f
Locus control regions, 387 532f Mannose-binding protein, deficiency of, 533
Long interspersed repeat sequences Mannose 6-phosphate/mannose 6-P signal,
Lysosomal hydrolases, deficiencies of,
(LINEs), 321–322 532–533, 533t 526
Looped domains, chromatin, 316, 318, in I-cell disease, 531, 532, 532f
Lysosomes in protein flow, 507, 508t
319f in oligosaccharide processing, 524 Mannosidosis, 532–533, 533t
Loops (protein conformation), 32–33 protein entry into, 507, 507f, 508t MAP (mitogen-activated protein) kinase
Loose connective tissue, keratan sulfate I in, disorders associated with defects in, in insulin signal transmission, 466f, 467
512t, 513 in Jak/STAT pathway, 467
545 Maple syrup urine disease (branched-chain
Low-density lipoprotein receptor-related Lysozyme, 621t
Lysyl hydroxylase ketonuria), 259
protein, 206 Marasmus, 80, 237, 478, 478–479
in chylomicron remnant uptake, diseases caused by deficiency of, 538t Marble bone disease (osteopetrosis), 552
in hydroxylysine synthesis, 240, 537 Marfan syndrome, fibrillin mutations
208–209, 209f Lysyl oxidase, 537, 539
Low-density lipoproteins, 205, 206t Lytic pathway, 379, 379f causing, 539–540, 540f
D-Lyxose, 104f, 105t Maroteaux-Lamy syndrome, 546t
apolipoproteins of, 206, 206t Mass spectrometry, 27, 27f
metabolism of, 209, 210f Mac-1, 529, 529t
ratio of to high-density lipoproteins, α2-Macroglobulin, 583t, 590, 624 covalent modifications detected by, 27,
27f, 27t
atherosclerosis and, 227 antithrombin activity of, 603
receptors for, 209 Macromolecules, cellular transport of, for glycoprotein analysis, 514, 515t
tandem, 27
in chylomicron remnant uptake, 428–431, 429f, 430f transcript-protein profiling and, 412
208–209, 209f Mad cow disease (bovine spongiform Mast cells, heparin in, 545
Matrix
in cotranslational insertion, 505–506, encephalopathy), 37 extracellular, 535–555. See also specific
506f Magnesium, 496t
component
regulation of, 223 in chlorophyll, 270 mitochondrial, 92, 93f, 130
Low-energy phosphates, 83 in extracellular and intracellular fluid, Matrix-assisted laser-desorption (MALDI),
β-LPH. See β-Lipotropin
LRP. See Low-density lipoprotein 416, 416t in mass spectrometry, 27
Major groove, in DNA, 305f, 306 Matrix-processing peptidase, 499
receptor-related protein Matrix proteins, 499
L-tryptophan dioxygenase (tryptophan operon model and, 378
Malate, 132f, 133 diseases caused by defects in import of,
pyrrolase), 89 Malate dehydrogenase, 132f, 133 503
LTs. See Leukotrienes Malate shuttle, 99, 100f
Lung surfactant, 115, 197 MALDI. See Matrix-assisted laser-desorption Maxam and Gilbert’s method, for DNA
Maleylacetoacetate, in tyrosine catabolism, sequencing, 404–405
deficiency of, 115, 202
Luteinizing hormone (LH), 437, 438, 439f 254f, 255 Maximal velocity (Vmax)
LXs. See Lipoxins Malic enzyme, 156t, 157 allosteric effects on, 75–76
LXXLL motifs, nuclear receptor inhibitors affecting, 68, 68f, 69f
in NADPH production, 176, 176f Michaelis-Menten equation in
coregulators, 473 Malignancy/malignant cells. See determination of, 65–66, 66f
Lyases, 50 substrate concentration and, 64, 64f
Cancer/cancer cells
in steroid synthesis, 440–442, 441f, Malignant hyperthermia, 556, 564–565, McArdle’s disease/syndrome, 152t, 573
443f Mechanically gated ion channels, 568t
565f, 569t Mediator-related proteins, 472t, 473
Lymphocyte homing, selectins in, 528–530, Malonate Medicine
529f, 529t, 530f
respiratory chain affected by, 95, 96f preventive, biochemical research
Lymphocytes. See also B lymphocytes; succinate dehydrogenase inhibition by, affecting, 2
T lymphocytes
67–68, 67f relationship of to biochemistry, 1–4, 3f
recombinant DNA technology in study Malonyl-CoA, in fatty acid synthesis, 173, Medium-chain acyl-CoA dehydrogenase,
of, 624
174f deficiency of, 188
Lysine, 16t Malonyl transacylase, 173, 174f, 175f Megaloblastic anemia
catabolism of, 256f, 258 Maltase, 475
pI of, 17 Maltose, 106–107, 107f, 107t folate deficiency causing, 482t, 492, 610t
requirements for, 480 Mammalian target of rapamycin (mTOR), vitamin B12 deficiency causing, 482t,

Lysine hydroxylase, vitamin C as coenzyme in insulin signal transmission, 492, 494, 610t
for, 496 466f, 467 Melanocyte-stimulating hormone (MSH),
Mammotropin. See Prolactin
Lysis, cell, complement in, 596 Manganese, 496t 453, 453f
Lysogenic pathway, 379, 379f Mannosamine, 169, 171f MELAS (mitochondrial encephalomyopa-
Lysolecithin (lysophosphatidylcholine), D-Mannosamine, 106
Mannose, in glycoproteins, 516t thy with lactic acidosis and
116, 116f stroke-like episodes), 100–101
metabolism of, 200–201, 201f
Lysophosphatidylcholine. See Lysolecithin
Lysophospholipase, 200, 201f
Lysophospholipids, 116, 116f
Lysosomal degradation pathway, defect in

in lipidoses, 203

Melting point, of amino acids, 18 6-Mercaptopurine, 290, 291f INDEX / 673
Melting temperature/transition Mercapturic acid, 629
Mercuric ions, pyruvate metabolism control of quantity and, 73–74
temperature, 305, 422 covalent modification and, 74, 76,
Membrane attack complex, 596 affected by, 142
Membrane fatty acid-transport protein, 207 Meromyosin 77–78, 78f
Membrane proteins, 419, 420t, 514. See rate-limiting reactions and, 73
heavy, 560f, 561, 561f at subcellular level, 126, 127f
also Glycoproteins light, 560–561, 560f at tissue and organ levels, 124–126, 125f,
association of with lipid bilayer, 419 Messenger RNA (mRNA), 307, 309–310,
flow of, 507, 507f, 508t 126f, 235t
integral, 30, 420, 421f 310f, 311f, 341, 342t, 359. See of xenobiotics, 626–632
mutations affecting, diseases caused by, also RNA Metachromatic leukodystrophy, 203t
alternative splicing and, 354, 354f, Metal-activated enzymes, 50
431–432, 432f, 432t 393–394, 636 Metal ions, in enzymatic reactions, 50
peripheral, 420–421, 421f codon assignments in, 358, 359t Metalloenzymes, 50
red cell, 614–617, 615f, 616f, 616t editing of, 356 Metalloflavoproteins, 86–87
structure of, dynamic, 419 expression of, detection of in gene Metalloproteins, 30
Membrane transport, 423, 423t, 424f, isolation, 635t Metallothioneins, 588
modification of, 355–356 Metaphase chromosomes, 317f, 318, 319t
426–431, 426f. See also specific nucleotide sequence of, 358 Metastasis
mechanism mutations caused by changes in, glycoproteins and, 514, 526, 530t, 531
Membranes, 415–433 361–363, 361f, 362f, 364f membrane abnormalities and, 432t
artificial, 421–422 polycistronic, 376 Methacrylyl-CoA, catabolism of, 262f
assembly of, 511–513, 512f, 512t recombinant DNA technology and, 397 Methemoglobin, 46, 363, 613–614
asymmetry of, 416, 419–420 relationship of to chromosomal DNA, Methemoglobinemia, 46, 614
bilayers of, 418–419, 418f, 419f 321f Methionine, 15t, 264, 266f
membrane protein association and, 419 stability of, regulation of gene expression active (S-adenosylmethionine), 258f,
biogenesis of, 511–513, 512f, 512t and, 394–395, 394f
cholesterol in, 417 transcription starting point and, 342 259, 264, 266f, 289, 290f, 290t
fluid mosaic model and, 422 variations in size/complexity of, 397, catabolism of, 258f, 259, 259f
depolarization of, in nerve impulse 399t requirements for, 480
transmission, 428 Metabolic acidosis, ammonia in, 245 Methionine synthase, 492, 494
function of, 415–416, 421–422 Metabolic alkalosis, ammonia in, 245 Methotrexate, 296–297, 494
fluidity affecting, 422 Metabolic fuels, 231–236. See also Digestion dihydrofolate/dihydrofolate reductase
glycosphingolipids in, 417 clinical aspects of, 236
Golgi apparatus in synthesis of, 509 diet providing, 474, 478 affected by, 296–297, 494
intracellular, 415 in fed and starving states, 232–234, Methylation
lipids in, 416–418 233f, 234f, 234t
amphipathic, 119, 120f, 417–418, 417f interconvertability of, 231–232 in covalent modification, mass increases
mutations affecting, diseases caused by, Metabolic pathway/metabolite flow, 122, and, 27t
431–432, 432f, 432t 122–124. See also specific type
phospholipids in, 114–116, 115f, and Metabolism of deoxycytidine residues, gene
416–417, 417f flux-generating reactions in, 129 expression affected by, 383
plasma. See Plasma membrane nonequilibrium reactions in, 128–129
protein:lipid ratio in, 416, 416f regulation of, 72, 73f, 126–129, 128f in glycoprotein analysis, 515t
proteins in, 419, 420t. See also covalent modification in, 79 of xenobiotics, 626, 630
Membrane proteins unidirectional nature of, 72, 73f β-Methylcrotonyl-CoA, catabolism of, 261f
red cell, 614–617, 615f, 615t, 616f, 616t Metabolism, 81, 122–129, 235t. See also 5-Methylcytosine, 287, 289f
hemolytic anemias and, 619, 620t specific type and Catalysis; α-Methyldopa, 446
selectivity of, 415, 423–426, 423t, 424f, Metabolic pathway Methylene tetrahydrofolate, 493, 493f
425f, 426t blood circulation and, 124–126, 125f, in folate trap, 493f, 494
sterols in, 417 126f 7-Methylguanine, 289f
structure of, 416–421, 416f group transfer reactions in, 8 Methylhistidine, 576
asymmetry and, 416, 419–420 inborn errors of, 1, 249 in Wilson’s disease, 265
fluid mosaic model of, 421f, 422 integration of, metabolic fuels and, Methylmalonic aciduria, 155
Menadiol, 486, 487f 231–236 Methylmalonyl-CoA, accumulation of in
Menadiol diacetate, 486, 488f regulation of, 72, 73f, 126–129, 128f
Menadione, 486. See also Vitamin K allosteric and hormonal mechanisms vitamin B12 deficiency, 492
Menaquinone, 482t, 486, 488f. See also in, 74, 74–76, 75f, 128f, 129 Methylmalonyl-CoA isomerase (mutase), in
Vitamin K enzymes in, 126–129, 128f
Menkes disease, 588 allosteric regulation and, 74, propionate metabolism, 155,
MEOS. See Cytochrome P450-dependent 74–76, 75f, 128f, 129 155f, 492
microsomal ethanol oxidizing compartmentation and, 72–73 Methylmalonyl-CoA mutase (isomerase),
system 155, 155f, 492
Methylmalonyl-CoA racemase, in propi-
onate metabolism, 155, 155f
Methyl pentose, in glycoproteins, 109t
Methyl-tetrahydrofolate, in folate trap,
493f, 494
Mevalonate, synthesis of, in cholesterol
synthesis, 219, 220f, 221f, 222f

674 / INDEX Mitochondrial encephalomyopathies, with Monounsaturated fatty acids, 112, 113t. See
lactic acidosis and stroke-like also Fatty acids; Unsaturated fatty
Mg. See Magnesium episodes (MELAS), 100 acids
Micelles, 418, 418f
Mitochondrial genome, 499 dietary, cholesterol levels affected by, 227
amphipathic lipids forming, 119, 120f, Mitochondrial glycerol-3-phosphate synthesis of, 191, 191f
418, 418f Morquio syndrome, 546t
dehydrogenase, 87 MPP. See Matrix-processing peptidase
in lipid absorption, 475 Mitochondrial membrane proteins, muta- MPS. See Mucopolysaccharidoses
Michaelis constant (Km), 65 MRE. See Mineralocorticoid response
tions of, 431
allosteric effects on, 75–76 Mitochondrial membranes, 92, 93f element
binding constant approximated by, 66 mRNA. See Messenger RNA
enzymatic catalysis rate and, 65–66, 66f, enzymes as markers and, 92 MRP2. See Multidrug resistance-like
exchange transporters and, 98–100, 98f,
72, 73f protein 2
inhibitors affecting, 68, 69f 99f MSH. See Melanocyte-stimulating hormone
Michaelis-Menten equation in protein insertion in, 501 MstII, 399t
Mitochondrial myopathies, fatal infantile,
determination of, 65–66, 66f in sickle cell disease, 409, 410f
Michaelis-Menten equation, 65 and renal dysfunction, oxidore- mtDNA. See Mitochondrial DNA
ductase deficiency causing, 100 mTOR, in insulin signal transmission,
Bi-Bi reactions and, 70, 70f Mitogen-activated protein (MAP) kinase
regulation of metabolite flow and, 72, in insulin signal transmission, 466f, 466f, 467
467 Mucins, 519–520, 520t
73f in Jak/STAT pathway, 467
Microfilaments, 576–577 Mitotic spindle, microtubules in formation genes for, 520
α2-Microglobulin, 583t of, 577 O-glycosidic linkages in, 518, 519–520,
Microsatellite instability, 322 Mixed-function oxidases, 89–90, 627. See
Microsatellite polymorphism, 322, 411, also Cytochrome P450 system 519f
ML. See Mucolipidoses repeating amino acid sequences in, 519,
413 MOAT. See Multispecific organic anion
Microsatellite repeat sequences, 322, 413 transporter 520f
Microsomal elongase system, 177, 177f Modeling, molecular, in protein structure Mucolipidoses, 546–547, 546t
Microsomal fraction, cytochrome P450 analysis, 36 Mucopolysaccharides, 109, 109f
Molecular biology, 1. See also Recombinant Mucopolysaccharidoses, 545–547, 546t,
isoforms in, 627 DNA/recombinant DNA
Microtubules, 577 technology 547f
Migration, cell, fibronectin in, 540 in primary structure determination, Mucoproteins. See Glycoproteins
Milk (lactose) intolerance, 102, 474, 475 25–26 Mucus, 519–520
Mineralocorticoid response element, 459t Molecular chaperones. See Chaperones Multidrug resistance-like protein 2, in
Mineralocorticoids, 437 Molecular genetics, 1, 396. See also
Recombinant DNA/recombinant bilirubin secretion, 280
receptor for, 471 DNA technology Multipass membrane protein, anion
synthesis of, 438–440, 441f Molecular modeling, in protein structure
Minerals, 2, 496–497, 496t analysis, 36 exchange protein as, 615, 615f,
digestion and absorption of, 477–478 Molecular motors, 577 616t
Minor groove, in DNA, 305f, 306 Molybdenum, 496t Multiple myeloma, 595
Mismatch repair of DNA, 336, 336f, 336t Monoacylglycerol acyltransferase, 198f, 199 Multiple sclerosis, 202
colon cancer and, 336 Monoacylglycerol pathway, 198f, 199, Multiple sulfatase deficiency, 203
Missense mutations, 361, 362–363, 362f 475–477, 476f Multisite phosphorylation, in glycogen
familial hypertrophic cardiomyopathy 2-Monoacylglycerols, 198f, 199 metabolism, 151
Monoclonal antibodies, hybridomas in Multispecific organic anion transporter, in
caused by, 569–570, 570f production of, 595–596, 596f bilirubin secretion, 280
MIT. See Monoiodotyrosine Monoglycosylated core structure, calnexin Muscle, 556–576, 557f. See also Cardiac
Mitchell’s chemiosmotic theory. See binding and, 526 muscle; Skeletal muscle
Monoiodotyrosine (MIT), 447, 448f, 449 ATP in, 556, 561–562, 573–574, 575f
Chemiosmotic theory Monomeric proteins, 34 contraction of. See Muscle contraction
Mitochondria Mononucleotides, 287 in energy transduction, 556–559, 557f,
“salvage” reactions and, 294, 295f, 297f 558f, 559f
ALA synthesis in, 270, 273f Monooxygenases, 89–90. See also fibers in, 556
citric acid cycle in, 122, 122f, 123f, 124f, Cytochrome P450 system glycogen in, 145, 146t
in metabolism of xenobiotics, 626 metabolism in, 125, 125f, 235t, 576t
126, 127f, 130, 133–135, 134f Monosaccharides, 102. See also specific type glycogen, 145
fatty acid oxidation in, 180–181, 181f and Glucose lactate production and, 139
ion transport in, 99 absorption of, 475, 475f as protein reserve, 576
protein synthesis and import by, physiologic importance of, 104–105, 105t proteins of, 566t. See also Actin; Myosin;
Titin
499–501, 501t Muscle contraction, 556, 558f, 561–565,
respiration rate of, ADP in control of, 564t
ATP hydrolysis in, 561–562, 561f
94–95, 97t, 98f in cardiac muscle, 566–568
respiratory chain in, 92. See also

Respiratory chain
Mitochondrial cytochrome P450, 89–90,

627. See also Cytochrome P450
system
Mitochondrial DNA, 322–323, 322f,
323t

regulation of Myocardial infarction, lactate INDEX / 675
actin-based, 562–563 dehydrogenase isoenzymes in
calcium in, 562 diagnosis of, 57, 57t, 58f regulation of, 526–527, 527t
in cardiac muscle, 566–568 tunicamycin affecting, 527, 527t
sarcoplasmic reticulum and, Myofibrils, 556, 557f, 558f Na. See Sodium
563–564, 563f, 564f Myoglobin, 40–48 Na+-Ca2+ exchanger, 463
in smooth muscle, 570–571, 571f Na+-K+ ATPase, 427–428, 428f
myosin-based, 570 α-helical regions of, 40, 41f in glucose transport, 428, 429f
myosin light chain kinase in, β subunits of hemoglobin and, 42 NAD+ (nicotinamide adenine dinucleotide),
570–571, 571f oxygen dissociation curve for, 41–42, 42f
oxygen stored by, 40, 41–42, 42f, 573 87, 490, 490f
relaxation phase of, 561, 564, 564t Myoglobinuria, 47 absorption spectrum of, 56, 56f
in smooth muscle Myokinase (adenylyl kinase), 84 in citric acid cycle, 133
calcium in, 571 deficiencies of, 151–152 as coenzyme, 87, 89f, 290t
nitric oxide in, 571–573, 573f in gluconeogenesis regulation, 157 NADH
as source of ATP in muscle, 573, 575f absorption spectrum of, 56, 56f
sliding filament cross-bridge model of, Myopathies, 92 extramitochondrial, oxidation of, 99,
557–559, 558f mitochondrial, 100–101
100f
in smooth muscle, 570–573 fatal infantile, and renal dysfunction, fatty acid oxidation yielding, 181
tropomyosin and troponin in, 562 oxidoreductase deficiency in pyruvate dehydrogenase regulation,
Muscle fatigue, 136 causing, 100
Muscle phosphorylase, 147 141–142, 142f
absence of, 152t Myophosphorylase deficiency, 152t NADH dehydrogenase, 87, 93
activation of Myosin, 557, 559, 560f NADP+ (nicotinamide adenine dinucleotide

calcium/muscle contraction and, in muscle contraction, 557–559, 558f, phosphate), 87, 490
148 561–562, 561f, 562f as coenzyme, 87, 89f, 290t
in pentose phosphate pathway, 163,
cAMP and, 147–148, 149f regulation of smooth muscle
Muscular dystrophy, Duchenne, 556, contraction and, 570 164f, 165f
NAD(P)+-dependent dehydrogenases, in
565–566, 566f in striated versus smooth muscle, 572t
Mutagenesis, site-directed, in enzyme study, structure and function of, 560–561, 560f enzyme detection, 56
Myosin-binding protein C, 566t NADPH
58 Myosin (thick) filaments, 557, 558f
Mutations, 314, 323–326, 323f, 324f, Myosin head, 560, 560f in cytochrome P450 reactions, 90f, 627
conformational changes in, in muscle intramitochondrial, proton-translocating
325f
base substitution, 361, 361f, 362 contraction, 561 transhydrogenase and, 99
constitutive, 376 Myosin heavy chains, 560 for lipogenesis, 175f, 176, 176f
frameshift, 363, 364f pentose phosphate pathway and, 163,
familial hypertrophic cardiomyopathy
ABO blood group and, 619 caused by mutations in gene for, 164f, 165f, 169
gene conversion and, 325 569–570, 570f NADPH-cytochrome P450 reductase, 627
integration and, 324, 324f NADPH oxidase, 621t, 622–623
of membrane proteins, diseases caused Myosin light chain kinase, 570–571, 571f
Myosin light chains, 560 chronic granulomatous disease associated
by, 431–432, 432f, 432t with mutations in, 623, 623f
missense, 361, 362–363, 362f in smooth muscle contraction, 570
Myotonia congenita, 569t NCoA-1/NCoA-2 coactivators, 472, 472t
familial hypertrophic cardiomyopathy Myristic acid, 112t, 510 NCoR, 472t, 473
caused by, 569–570, 570f Myristylation, 510 NDPs. See Ribonucleoside diphosphates
Nebulin, 566t
mRNA nucleotide sequence changes caus- in covalent modification, mass increases NEFA (nonesterified fatty acids). See Free
ing, 361–363, 361f, 362f, 364f and, 27t
fatty acids
nonsense, 362 N-acetyl neuraminic acid, 169, 171f Negative nitrogen balance, 479
point, 361 in gangliosides, 201, 203f Negative regulators, of gene expression,
in glycoproteins, 169, 171f, 515, 516t
recombinant DNA technology in in mucins, 519f, 520 374, 375t, 378, 380
detection of, 408–409, 408f Negative supercoils, DNA, 306
N-linked glycoproteins, 518, 519f, NEM-sensitive factor (NSF), 509, 510f
recombination and, 323–324, 323f, 324f 521–527 Neonatal adrenoleukodystrophy, 503,
silent, 361
sister chromatid exchanges and, 325, 325f classes of, 521, 522f 503t
suppressor, 363 synthesis of, 521–527, 523f, 524f, 525f, Neonatal (physiologic) jaundice, 282–283
transition, 361, 361f Neonatal tyrosinemia, 255
transposition and, 324–325 526t Neonate, hypoglycemia in, 151
transversion, 361, 361f dolichol-P-P-oligosaccharide in, Nerve cells. See Neurons
Myasthenia gravis, 431 Nerve impulses, 428
Myelin sheets, 428 521–524, 523f Nervous system
Myeloma, 595 in endoplasmic reticulum and Golgi
Myeloma cells, hybridomas grown from, glucose as metabolic necessity for, 232
apparatus, 524–525, 526t thiamin deficiency affecting, 489
596, 596f glycan intermediates formed during, NESs. See Nuclear export signals
Myeloperoxidase, 612, 621t, 623 Net charge, of amino acid, 16–17, 17f
526 Net diffusion, 423

676 / INDEX Night blindness, vitamin A deficiency Nuclear genes, proteins encoded by, 499
causing, 482t, 483 Nuclear localization signal (NLS), 501,
NeuAc. See N-Acetylneuraminic acid
Neural tube defects, folic acid supplements Nitric oxide, 556, 571–573, 573f, 574t, 502f, 508t
607t Nuclear magnetic resonance (NMR)
in prevention of, 494
Neuraminic acid, 110, 116 clotting/thrombosis affected by, 607, spectroscopy
Neuraminidases 607t for glycoprotein analysis, 514, 515t
protein structure demonstrated by,
deficiency of, 532–533, 533t Nitric oxide synthases, 572–573, 573f, 574t
in glycoprotein analysis, 517 Nitrite, nitric oxide formation from, 572 35–36
influenza virus, 533 Nitrogen, amino acid (α-amino) Nuclear pore complexes, 501
Neurofilaments, 577t Nuclear proteins, O-glycosidic linkages in,
Neurologic diseases, protein conformation catabolism of, 242–248
end products of, 242–243 518
alterations and, 37 urea as, 242–243, 245–247, 246f Nuclear receptor coactivators
Neurons, membranes of L-glutamate dehydrogenase in,
244–245, 244f, 245f (NCoA-1/NCoA-2), 472, 472t
impulses transmitted along, 428 Nuclear receptor corepressor (NCoR), 472t,
ion channels in, 424, 425f Nitrogen balance, 479
synaptic vesicle fusion with, 511 Nitroglycerin, 572 473
Neuropathy, sensory, in vitamin B6 excess, NLS. See Nuclear localization signal Nuclear receptor superfamily, 436, 469,
NMR. See Nuclear magnetic resonance
491 469–471, 471f, 472t
Neutral lipids, 111 (NMR) spectroscopy Nucleases, 8, 312
Neutropenia, 610 NO. See Nitric oxide
Neutrophils, 620–624 NO synthase. See Nitric oxide synthase active chromatin and, 316
Noncoding regions, in recombinant DNA Nucleic acids. See also DNA; RNA
activation of, 621–622
biochemical features of, 620t technology, 397, 398f bases of, 287–289, 288t
enzymes and proteins of, 621t Noncoding strand, 304 dietarily nonessential, 293
in infection, 620 Noncompetitive inhibition, competitive digestion of, 312
in inflammation, 620, 621t structure and function of, 303–313
inhibition differentiated from, Nucleolytic processing, of RNA, 352
integrins and, 620–621, 622t 67–69, 67f, 68f, 69f Nucleophile, water as, 7–8
selectins and, 528–529, 529t, 530f Noncovalent assemblies, in membranes, 416 Nucleophilic attack, in DNA synthesis,
proteinases of, 623–624, 624t Noncovalent forces
respiratory burst and, 622–623 in biomolecule stabilization, 6 328, 329f
NF-κB pathway, 468, 468f, 469f peptide conformation and, 20 Nucleoplasmin, 315
Niacin, 482t, 490, 490f. See also Nonequilibrium reactions, 128–129 Nucleoproteins, packing of, 318, 319t, 320f
citric acid cycle regulation and, 135 Nucleosidases (nucleoside phosphorylases),
Nicotinamide; Nicotinic acid glycolysis regulation and, 140, 153–155
in citric acid cycle, 133 Nonesterified fatty acids. See Free fatty acids purine, deficiency of, 300
deficiency of, 482t, 490 Nonfunctional plasma enzymes, 57. See also Nucleoside diphosphate kinase, 85
excess/toxicity of, 490 Enzymes Nucleoside triphosphates
Nick translation, 413 in diagnosis and prognosis, 57, 57t
Nickel, 496t Nonheme iron, 92, 95f, 585 group transfer potential of, 289–290,
Nicks/nick-sealing, in DNA replication, Nonhistone proteins, 314 289f, 290f, 290t
Non-insulin dependent diabetes mellitus
332, 332f (NIDDM/type 2), 161 nonhydrolyzable analogs of, 291, 292f
Nicotinamide, 482t, 490, 490f. See also Nonoxidative phase, of pentose phosphate in phosphorylation, 85
pathway, 163–166 Nucleosides, 286–287, 288t
Niacin Nonrepetitive (unique-sequence) DNA, Nucleosomes, 314, 315–316, 315f
coenzymes derived from, 50–51 320, 320–321 Nucleotide excision-repair of DNA, 336,
Nonsense codons, 359, 361, 363
dehydrogenases and, 87, 89f Nonsense mutations, 361 337, 338f
excess/toxicity of, 490 Nonsteroidal anti-inflammatory drugs Nucleotide sugars, in glycoprotein biosyn-
Nicotinamide adenine dinucleotide cyclooxygenase affected by, 193
prostaglandins affected by, 190 thesis, 516–517, 516t, 520, 521t
(NAD+), 87, 490, 490f Norepinephrine, 439f, 447, 447f. See also Nucleotides, 286–292, 288t. See also
absorption spectrum of, 56, 56f Catecholamines
in citric acid cycle, 133 synthesis of, 267, 267f, 445–447, 447f Purine; Pyrimidines
as coenzyme, 87, 89f, 290t in thermogenesis, 217, 217f adenylyl kinase (myokinase) in
Nicotinamide adenine dinucleotide Northern blot transfer procedure, 305–306,
403, 404f, 413 interconversion of, 84
phosphate (NADP+), 87, 490 in gene isolation, 635t as coenzymes, 290, 290t
as coenzyme, 87, 89f, 290t NPCs. See Nuclear pore complexes DNA, deletion/insertion of, frameshift
in pentose phosphate pathway, 163, NSF. See NEM-sensitive factor
Nuclear export signals, 503 mutations and, 363, 364f
164f, 165f metabolism of, 293–302
Nicotinic acid, 482t, 490, 490f. See also in mRNA, 358

Niacin mutations caused by changes in,
as hypolipidemic drug, 229 361–363, 361f, 362f, 364f
NIDDM. See Non-insulin dependent
physiologic functions of, 289
diabetes mellitus as polyfunctional acids, 290
Nidogen (entactin), in basal lamina, 540 polynucleotides, 291–292
Niemann-Pick disease, 203t synthetic analogs of, in chemotherapy,

290–291, 291f
ultraviolet light absorbed by, 290

Nucleus (cell), importins and exportins in Oncogenes, 1 INDEX / 677
transport and, 501–503, 502f cyclins and, 334
Overnutrition, 478–479
Nutrition, 474–480. See also Diet Oncoproteins, Rb protein and, 334 Oxaloacetate
biochemical research affecting, 2 Oncotic (osmotic) pressure, 580, 584
lipogenesis regulated by, 177–178 Oncoviruses, cyclins and, 334 in amino acid carbon skeleton
Open complex, 345 catabolism, 249, 250f
Nutritional deficiencies, 474 Operator locus, 377–378, 377f, 378
in AIDS and cancer, 479 Operon/operon hypothesis, 375, 376–378, in aspartate synthesis, 237–238, 238f
in citric acid cycle, 126, 127f, 130, 131f,
Nutritionally essential amino acids, 124, 376f, 377f
237t, 480. See also Amino acids Optical activity/isomer, 104 133, 134f, 135
ORC. See Origin replication complex Oxalosis, 170
Nutritionally essential fatty acids, 190. See ORE. See Origin replication element Oxidases, 86, 86–87, 87f. See also specific
also Fatty acids Ori (origin of replication), 326, 327f, 413
Origin replication complex, 326 type
abnormal metabolism of, 195–196 Origin replication element, 326 ceruloplasmin as, 587
deficiency of, 191–192, 194–195 Origin of replication (ori), 326, 327f, copper in, 86
Nutritionally nonessential amino acids, flavoproteins as, 86–87, 88f
413 mixed-function, 89–90, 627. See also
124, 237, 237t, 480 Ornithine, 265, 266f
synthesis of, 237–241 Cytochrome P450 system
catabolism of, 250, 251f Oxidation, 86–91
OR. See Right operator in urea synthesis, 245, 246–247, 246f,
O blood group substance, 618–619, 619f definition of, 86
O gene, 618–619 247 dehydrogenases in, 87–88, 88f, 89f
O-glycosidic linkage Ornithine δ-aminotransferase, mutations fatty acid, 180–189. See also Ketogenesis

of collagen, 537 in, 250 acetyl-CoA release and, 123–124,
of proteoglycans, 542–543 Ornithine-citrulline antiporter, defective, 123f, 181–183, 181f, 182f
O-linked glycoproteins, 518, 518–520,
250 β, 181–183, 181f, 182f
519f, 520f, 520t Ornithine transcarbamoylase/L-Ornithine ketogenesis regulation and,
synthesis of, 520, 521t 186–187, 187f, 188f
O-linked oligosaccharides, in mucins, transcarbamoylase modified, 183, 183f
deficiency of, 247, 300
519–520, 519f, 520f in urea synthesis, 246–247, 246f clinical aspects of, 187–189
Obesity, 80, 205, 231, 474, 478 Orosomucoid (α1-acid glycoprotein), hypoglycemia caused by impairment

lipogenesis and, 173 583t of, 187–188
Octamers, histone, 315, 315f Orotate phosphoribosyltransferase, 296, in mitochondria, 180–181, 181f
Oculocerebrorenal syndrome, 512t hydroperoxidases in, 88–89
1,25(OH)2-D3. See Calcitriol 297, 298f oxidases in, 86–87, 87f, 88f
3β-OHSD. See 3β-Hydroxysteroid Orotic aciduria, 300, 301 oxygen toxicity and, 90–91, 611–613,
Orotidine monophosphate (OMP), 296,
dehydrogenase 613t
Okazaki fragments, 327, 330, 331f 298f oxygenases in, 89–90, 90f
Oleic acid, 112, 112f, 113, 113t, 114f, 190f Orotidinuria, 301 redox potential and, 86, 87t
Orphan receptors, 436, 471 Oxidation-reduction (redox) potential, 86,
synthesis of, 191, 191f Osmotic fragility test, 617
Oligomers, import of by peroxisomes, 503 Osmotic lysis, complement in, 596 87t
Oligomycin, respiratory chain affected by, Osmotic (oncotic) pressure, 580, 584 Oxidative decarboxylation, of
Osteoarthritis, 535, 551t
95, 96f, 97f α-ketoglutarate, 131, 132f
Oligonucleotide proteoglycans in, 548 Oxidative phase, of pentose phosphate
Osteoblasts, 549, 549f, 550
definition of, 413 Osteocalcin, 488, 496, 548t pathway, 163, 164f, 165f
in primary structure determination, 26 Osteoclasts, 549–550, 549f, 550f Oxidative phosphorylation, 83, 92–101,
Oligosaccharide:protein transferase, 523 Osteocytes, 549, 549f
Oligosaccharide branches (antennae), 521 Osteogenesis imperfecta (brittle bones), 122. See also Phosphorylation;
Oligosaccharide chains Respiratory chain
glycoprotein, 514, 515t, 581–582 551–552, 551t chemiosmotic theory of, 92, 95–97, 97f
Osteoid, 549f, 550 clinical aspects of, 100–101
in N-glycosylation, 524, 525f Osteomalacia, 482t, 484, 485, 551t muscle generation of ATP by, 573,
regulation of, 526 Osteonectin, 548t 574–576, 575f, 575t
Osteopetrosis (marble bone disease), 552 poisons affecting, 92, 95, 96f
sugars in, 515, 516t Osteoporosis, 485, 551t, 552 Oxidative stress, 612
glycosaminoglycans, 543 Osteopontin, 548t Oxidoreductases, 49, 86. See also specific type
Oligosaccharide processing, 521, 524, 525f Ouabain, 106 deficiency of, 100
Golgi apparatus in, 509 Oxidosqualene:lanosterol cyclase, 220, 222f
regulation of, 526, 527f Na+-K+ ATPase affected by, 428 Oxygen
Oligosaccharides, 102 Outer mitochondrial membrane, 92, 93f binding, 42, 42f. See also Oxygenation
O-linked, in mucins, 519–520, 519f, Bohr effect and, 44, 45f
protein insertion in, 501 histidines F8 and E7 in, 40, 41f
520f Ovary, hormones produced by, 437, hemoglobin affinities (P50) for, 42–43,
OMP (orotidine monophosphate), 296, 43f
442–445, 444f, 445f myoglobin in storage of, 40, 41–42, 42f,
298f 573

678 / INDEX storage/secretion of, 453, 454t Periodic acid-Schiff reagent, in glycoprotein
synthesis of, 450, 451f analysis, 515t
Oxygen (cont.) Paroxysmal nocturnal hemoglobinuria,
reductive activation of, 627 Periodic hyperlysinemia, 258
transport of, ferrous iron in, 40–41 432t, 528, 530t, 531, 531f Periodic paralysis
Partition chromatography, for protein/
Oxygen dissociation curve, for myoglobin hyperkalemic, 569t
and hemoglobin, 41–42, 42f peptide purification, 21 hypokalemic, 569t
Passive diffusion/transport, 423, 423t, 424f Peripheral proteins, 420–421, 421f
Oxygen radicals. See Free radicals Pasteur effect, 157 Peripherin, 577t
Oxygen toxicity, superoxide free radical pBR322, 402, 402t, 403f Permeability coefficients, of substances in
PCR. See Polymerase chain reaction
and, 90–91, 611–613, 613t. See PDH. See Pyruvate dehydrogenase lipid bilayer, 418, 419f
also Free radicals PDI. See Protein disulfide isomerase Pernicious anemia, 482t, 492
Oxygenases, 86, 89–90 PECAM-1, 529, 529t Peroxidases, 88, 192
Oxygenation of hemoglobin Pedigree analysis, 409, 410f Peroxidation, lipid, free radicals produced
conformational changes and, 42, 43f, 44f Pellagra, 482t, 490
apoprotein, 42 Penicillamine, for Wilson disease, 589 by, 118–119, 120f
2,3-bisphosphoglycerate stabilizing, Pentasaccharide, in N-linked glycoproteins, Peroxins, 503
45, 45f Peroxisomal-matrix targeting sequences
high altitude adaptation and, 46 521, 522f
mutant hemoglobins and, 46 Pentose phosphate pathway, 123, 163–166, (PTS), 503, 508t
Oxysterols, 119 Peroxisomes, 89, 503
164f, 165f, 167f
Pi, in muscle contraction, 561, 561f cytosol as location for reactions of, 163 absence/abnormalities of, 503, 503t
P50, hemoglobin affinity for oxygen and, enzymes of, 156t in Zellweger’s syndrome, 188, 503
erythrocyte hemolysis and, 169–170,
42–43, 43f biogenesis of, 503
p53 protein/p53 gene, 339 613 in fatty acid oxidation, 182–183
p160 coactivators, 472, 472t impairment of, 169–170 Pfeiffer syndrome, 551t
p300 coactivator/CPB/p300, 461, 468, NADPH produced by, 163, 164f, PFK-1. See Phosphofructokinase
PGHS. See Prostaglandin H synthase
469, 469f, 472, 472t 165f PGIs. See Prostacyclins
P450 cytochrome. See Cytochrome P450 for lipogenesis, 175f, 176, 176f PGs. See Prostaglandins
nonoxidative phase of, 163–166 pH, 9–13. See also Acid-base balance
system oxidative phase of, 163, 164f, 165f amino acid net charge and, 16, 17f
P450scc (cytochrome P450 side chain ribose produced by, 163, 164f buffering and, 11–12, 12f. See also
Pentoses, 102, 102t
cleavage enzyme), 438, 440f, 442 in glycoproteins, 109t Buffers
p/CIP coactivator, 472, 472t physiologic importance of, 104–105, calculation of, 9–10
P component, in amyloidosis, 590 definition of, 9
P-selectin, 529t 105t enzyme-catalyzed reaction rate affected
PAC (P1-based) vector, 401–402, 402t, 413 Pentosuria, essential, 163, 170
PAF. See Platelet-activating factor PEPCK. See Phosphoenolpyruvate by, 64, 64f
PAGE. See Polyacrylamide gel isoelectric, amino acid net charge and, 17
carboxykinase Phage lambda, 378–383, 379f, 380f, 381f,
electrophoresis Pepsin, 477
Pain, prostaglandins in, 190 382f
Palindrome, 413 in acid-base catalysis, 52 Phages
Palmitate, 173, 173–174 Pepsinogen, 477
Palmitic acid, 112t Peptidases, in protein degradation, 242, for cloning in gene isolation, 635t
Palmitoleic acid, 113t, 190f in recombinant DNA technology, 401
Palmitoylation, in covalent modification, 243f Phagocytic cells, respiratory burst of,
Peptide bonds. See also Peptides
mass increases and, 27t 622–623
Pancreatic insufficiency, in vitamin B12 formation of, 7, 368 Phagocytosis, 429
partial double-bond character of, 19–20, Pharmacogenetics, 630, 631–632
deficiency, 492 Pharmacogenomics, 632, 638
Pancreatic islets, insulin produced by, 160 20f Phasing, nucleosome, 315–316
Pancreatic lipase, 475, 476f Peptides, 14–20, 439f. See also Amino Phenobarbital, warfarin interaction and,
Panproteinase inhibitor, α2-macroglobulin
acids; Proteins cytochrome P450 induction
as, 590 absorption of, 477 affecting, 628
Pantothenic acid, 173, 482t, 495, 495i amino acids in, 14, 19, 19f Phenylalanine, 16t
formation of, L-α-amino acids in, 14 catabolism of, 255–258, 255f
in citric acid cycle, 133 as hormone precursors, 449–453 in phenylketonuria, 255, 255f
coenzymes derived from, 51 intracellular messengers used by, requirements for, 480
deficiency of, 482t in tyrosine synthesis, 239, 240f
Papain, immunoglobulin digestion by, 591 457–468, 461t, 463t Phenylalanine hydroxylase
PAPS. See Adenosine 3′-phosphate- as polyelectrolytes, 19 defect in, 255
purification of, 21–24 localization of gene for, 407t
5′-phosphosulfate Peptidyl prolyl isomerase, 508 in tyrosine synthesis, 239, 240f
Parallel β sheet, 32, 33f Peptidylglycine hydroxylase, vitamin C as Phenylethanolamine-N-methyltransferase
Parathyroid hormone (PTH), 438, 450, (PNMT), 447, 447f
coenzyme for, 496
451f Peptidyltransferase, 368, 370t

Phenylisothiocyanate (Edman reagent), in in neutrophil activation, 621–622 INDEX / 679
protein sequencing, 25, 26f in platelet activation, 606–607, 606f
Phosphatidylinositol 3-kinase (PI-3 kinase) Phospholipase Cβ, in platelet activation,
Phenylketonuria, 255–258 in insulin signal transmission, 465, 466f 606, 606f
Phi (ϕ) angle, 31, 31f in Jak/STAT pathway, 467
Phosphagens, 83, 84f Phosphatidylserine, 115, 115f Phospholipase D, 200, 201f
Phosphatases in blood coagulation, 601 Phospholipases
membrane asymmetry and, 420
acid, diagnostic significance of, 57t Phosphocreatine, in muscle, 556 in glycoprotein analysis, 515t
alkaline Phosphodiester, 291 in phosphoglycerol degradation and
Phosphodiesterases, 291
in bone mineralization, 550 in calcium-dependent signal remodeling, 200–201, 201f
isozymes of, diagnostic significance of, Phospholipids, 111, 205
transduction, 463
57t in cAMP-dependent signal transduction, digestion and absorption of, 475–477,
in recombinant DNA technology, 476f
461, 462f
400t cAMP hydrolyzed by, 147 glycerol ether, synthesis of, 199, 200f
Phosphate transporter, 99, 99f Phosphoenolpyruvate, 156t in lipoprotein lipase activity, 207–208
Phosphates/phosphorus, 496t free energy of hydrolysis of, 82t in membranes, 114–116, 115f,
in gluconeogenesis, 133, 134f, 156t
exchange transporters and, 99, 99f, 100, Phosphoenolpyruvate carboxykinase 416–417, 417f, 419, 511
101f membrane asymmetry and, 420, 511
(PEPCK), 133, 134f in multiple sclerosis, 202
in extracellular and intracellular fluid, in gluconeogenesis regulation, 133, 134f, as second messenger precursors, 197
416t synthesis of, 198f
153, 154f Phosphoprotein phosphatases, in cAMP-
free energy of hydrolysis of, 82–83, 82t Phosphofructokinase/
high-energy, 83. See also ATP dependent signal transduction,
phosphofructokinase-1, 156t 462, 462f
in energy capture and transfer, 82–83, in gluconeogenesis regulation, 157 Phosphoproteins, in cAMP-dependent
82f, 82t, 83f in glycolysis, 137, 138f, 156t signal transduction, 461, 462f
Phosphoric acid, pK/pKa value of, 12t
as “energy currency” of cell, 83–85, regulation and, 140 Phosphorus. See Phosphates
84f, 85f muscle, deficiency of, 143, 152t Phosphorylase
Phosphofructokinase-2, 157, 158f in glycogen metabolism, 145–146,
symbol designating, 83 Phosphoglucomutase, in glycogen 146f
transport of, creatine phosphate regulation of, 148–150, 150–151,
biosynthesis, 145, 146f 150f, 151f
shuttle in, 100, 101f 6-Phosphogluconate dehydrogenase, 156t, liver, 147
low-energy, 83 deficiency of, 152t
Phosphatidate, 198f, 199 163, 164f, 165f muscle, 147
in triacylglycerol synthesis, 197, 197f, 3-Phosphoglycerate absence of, 152t
activation of
198, 198f, 199 in glycolysis, 137, 138f calcium/muscle contraction and,
Phosphatidate phosphohydrolase, 198f, 199 in serine synthesis, 238, 238f 148
Phosphatidic acid, 114, 115f, 416–417, Phosphoglycerate kinase, in glycolysis, 137, cAMP and, 147–148, 149f
Phosphorylase a, 147, 149f
417f 138f Phosphorylase b, 147, 149f
Phosphatidic acid pathway, 476f, 477 in erythrocytes, 140, 140f Phosphorylase kinase
Phosphatidylcholines (lecithins), 114–115, Phosphoglycerate mutase, in glycolysis, 137, calcium/calmodulin-sensitive, in
glycogenolysis, 148
115f 138f deficiency of, 152t
in cytochrome P450 system, 617 Phosphoglycerides, in membranes, protein phosphatase-1 affecting, 147
membrane asymmetry and, 420 Phosphorylase kinase a, 148, 149f
synthesis of, 197, 197f, 198f 416–417, 417f Phosphorylase kinase b, 148, 149f
Phosphatidylethanolamine (cephalin), 115, Phosphoglycerols Phosphorylation
in covalent modification, 76, 77–79, 78f,
115f lysophospholipids in metabolism of, 116, 78t
membrane asymmetry and, 420 116f mass increases and, 27t
synthesis of, 197, 197f multisite, in glycogen metabolism, 151
Phosphatidylglycerol, 115, 115f synthesis of, 197f, 198f, 199 oxidative. See Oxidative phosphorylation
Phosphatidylinositol/phosphatidylinositide, Phosphohexoseisomerase, in glycolysis, 137, in respiratory burst, 623
Photolysis reaction, in vitamin D synthesis,
115, 115f 138f 445
in blood coagulation, 601 Phosphoinositide-dependent kinase-1 Photosensitivity, in porphyria, 274
GPI-linked glycoproteins and, 527. Phototherapy, cancer, porphyrins in, 273
(PDK1), in insulin signal Phylloquinone, 482t, 486, 488f. See also
See also Glycosylphosphatidyli- transmission, 465 Vitamin K
nositol-anchored (GPI- Phospholipase A1, 200, 201f Physical map, 633, 634f
anchored/ GPI-linked) Phospholipase A2, 200, 201f
glycoproteins in platelet activation, 606f, 607
metabolism of, 464–465, 464f, 465f Phospholipase C, 200, 201f
as second messenger/second messenger in calcium-dependent signal transduction,
precursor, 115, 115f, 437, 437t, 464–465, 464f, 465f
457, 463–465, 463t, 464f, 465f in Jak/STAT pathway, 467
synthesis of, 197, 197f, 198f in respiratory burst, 623
Phosphatidylinositol 4,5-bisphosphate, 115,
464–465, 465f

680 / INDEX Plasma thromboplastin antecedent Polymerases
(PTA/factor XI), 599f, 600, 600t DNA, 326, 327–328, 327f, 328, 328t
Physiologic (neonatal) jaundice, 282–283 in recombinant DNA technology, 400t
Phytanic acid, Refsum’s disease caused by deficiency of, 601 RNA, DNA-dependent, in RNA
Plasma thromboplastin component synthesis, 342–343, 342f, 343t
accumulation of, 188
Phytase, 477 (PTC/factor IX), 599f, 600, 600t Polymorphisms, 407
Phytic acid (inositol hexaphosphate), calcium coumarin drugs affecting, 604 acetyltransferase, 630
deficiency of, 604 cytochrome P450, 628, 630t
absorption affected by, 477 Plasmalogens, 116, 117f, 199, 200f microsatellite, 322, 411, 413
Pi, 589. See also α1-Antiproteinase Plasmids, 400–401, 401f, 402, 402t, 403f, plasma protein, 582
pI (isoelectric pH), amino acid net charge restriction fragment length. See
413 Restriction fragment length
and, 17 for cloning in gene isolation, 635t polymorphisms
PI-3 kinase Plasmin, 604–605, 604f single nucleotide, 414
Plasminogen, 604
in insulin signal transmission, 465, 466f activators of, 604–605, 604f, 605, 605f, Polynucleotide kinase, in recombinant
in Jak/STAT pathway, 467 DNA technology, 400t
PIC. See Preinitiation complex 607t
PIG-A gene, mutations of in paroxysmal Platelet-activating factor, 197, 621t Polynucleotides, 291–292
posttranslational modification of, 289
nocturnal hemoglobinuria, 531, synthesis of, 198f, 199, 200f
531f Platelets, activation/aggregation of, 598, Polyol (sorbitol) pathway, 172
“Ping-Pong” mechanism, in facilitated Polypeptides
diffusion, 427, 427f 605–607, 606f
Ping-pong reactions, 69–70, 69f aspirin affecting, 607–608 receptors for, 436
Pinocytosis, 429–430 Pleckstrin, in platelet activation, 607 sequencing of
PIP2, in absorptive pinocytosis, 430 PLP. See Pyridoxal phosphate
Pituitary hormones, 437. See also specific PNMT. See Phenylethanolamine- cleavage in, 25, 26t
type Sanger’s determination of, 24–25
blood glucose affected by, 161 N-methyltransferase Polyphosphoinositide pathway, platelet
pK/pKa pOH, in pH calculation, 9
of amino acids, 15–16t, 17, 17f, 18 Point mutations, 361 activation and, 605–607
environment affecting, 18, 18t Polyprenoids, 118, 119f
medium affecting, 13 recombinant DNA technology in Polyribosomes (polysomes), 310, 370
of weak acids, 10–11, 11–12, 12t, 13, 17 detection of, 408–409, 408f, 409t
PKA. See Protein kinase A protein synthesis on, 498, 499f, 500f,
PKB. See Protein kinase B Poisons, oxidative phosphorylation/ 506
PKC. See Protein kinase C respiratory chain affected
PKU. See Phenylketonuria by, 92, 95, 96f plasma proteins, 581
Placenta, estriol synthesis by, 442 signal hypothesis of binding of,
Plaque hybridization, 403. See also Pol II
Hybridization phosphorylation of, 350–351 503–505, 504t, 505f
Plasma, 580 in preinitiation complex formation, Polysaccharides, 102, 107–110, 108f, 109f.
Plasma cells, immunoglobulins synthesized 351–352
in, 591 in transcription, 350–351 See also specific type
Plasma enzymes. See also Enzymes Polysomes. See Polyribosomes
diagnostic significance of, 57, 57t Polarity Polytene chromosomes, 318, 318f
Plasma lipoproteins. See Lipoproteins of DNA replication/synthesis, 330–331 Polyunsaturated fatty acids, 112, 113t. See
Plasma membrane, 415, 426–431, 426f. of protein synthesis, 364
See also Membranes of xenobiotics, metabolism and, 626 also Fatty acids; Unsaturated fatty
carbohydrates in, 110 acids
mutations in, diseases caused by, 431, Poly(A) tail, of mRNA, 309, 355–356 dietary, cholesterol levels affected by, 227
432t in initiation of protein synthesis, 365 eicosanoids formed from, 190, 192,
Plasma proteins, 514, 580–591, 581f, 583t. 193f, 194f
See also specific type and Polyacrylamide gel electrophoresis, for essential, 190, 190f
Glycoproteins protein/peptide purification, synthesis of, 191, 191f, 192f
in bone, 548t 24, 24f, 25f POMC. See Pro-opiomelanocortin
concentration of, 580 (POMC) peptide family
electrophoresis for analysis of, 580, 582f Polyadenylation sites, alternative, 394 Pompe’s disease, 152t
functions of, 583, 583t Polyamines, synthesis of, 265–266, 266f Porcine stress syndrome, 565
half life of, 582 Polycistronic mRNA, 376 Porphobilinogen, 270, 273f, 275f
in inflammation, 621t Polycythemia, 46 Porphyrias, 274–278, 277f, 277t
polymorphism of, 582 Polydystrophy, pseudo-Hurler, 532, 546t Porphyrinogens, 272
synthesis of Polyelectrolytes, peptides as, 19 accumulation of in porphyria, 274–278
in liver, 125, 581 Polyfunctional acids, nucleotides as, 290 Porphyrins, 270–278, 271f, 272f
on polyribosomes, 581 Polyisoprenoids, in cholesterol synthesis, absorption spectra of, 273–274, 277f
transport, 454–455, 454t, 455t, 583t heme synthesis and, 270–273, 273f,
220, 221f 274f, 275f, 276f
Polyisoprenol, in N-glycosylation, 521–522 reduced, 272
Polymerase chain reaction (PCR), 57, spectrophotometry in detection of,
273–274
405–406, 406f, 413, 414 Positive nitrogen balance, 479
in gene isolation, 635t
in microsatellite repeat sequence

detection, 322
in primary structure determination, 26

Positive regulators, of gene expression, 374, proteomics and, 28–29 INDEX / 681
375t, 378, 380 Sanger’s technique in determination of,
Promoter recognition specificity, 343
Posttranslational processing, 30, 37–39, 24–25 Promoters, in transcription, 342, 342f
38f, 371 Primary transcript, 342
Primases, DNA, 327, 327f, 328t alternative use of in regulation, 354–355,
of collagen, 537–538, 537t Primosome, 328, 414 355f, 393–394
in membrane assembly, 511–512 Prion diseases (transmissible spongiform
Posttranslational translocation, 499 bacterial, 345–346, 345f
Potassium, 496t encephalopathies), 37 eukaryotic, 346–349, 347f, 348f, 349f,
in extracellular and intracellular fluid, Prion-related protein (PrP), 37
Prions, 37 384
416, 416t Proaccelerin (factor V), 600t, 601, 602f Promotor site, in operon model, 377f, 378
permeability coefficient of, 419f Proaminopeptidase, 477 Proofreading, DNA polymerase, 328
Power stroke, 561 Probes, 402, 414. See also DNA probes Pro-opiomelanocortin (POMC) peptide
PPI. See Peptidyl prolyl isomerase
PPi. See Pyrophosphate, inorganic for gene isolation, 635t family, 452–453, 453f. See also
PR. See Progesterone, receptors for Probucol, 229 specific type
Pravastatin, 229 Procarcinogens, 626 Pro-oxidants, 612. See also Free radicals
PRE. See Progestin response element Processivity, DNA polymerase, 328 Proparathyroid hormone (proPTH), 450,
Pre-β-lipoproteins, 205, 206t, 210 Prochymotrypsin, activation of, 77, 77f 450f
Precursor proteins, amyloid, 590 Procollagen, 371, 496, 537 Propionate
Pregnancy Procollagen aminoproteinase, 537 blood glucose and, 159
estriol synthesis in, 442 Procollagen carboxyproteinase, 537 in gluconeogenesis, 154f, 155
fatty liver of, 188 Procollagen N-proteinase, disease caused by metabolism of, 155, 155f
hypoglycemia during, 161 Propionic acid, 112t
iron needs during, 586 deficiency of, 538t Propionyl-CoA
Pregnancy toxemia of ewes (twin lamb Proconvertin (factor VII), 599f, 600t, 601 fatty acid oxidation yielding, 182
methionine in formation of, 259, 259f
disease) coumarin drugs affecting, 604 Propionyl-CoA carboxylase, 155, 155f
fatty liver and, 212 Prodrugs, 626 Proproteins, 37–38, 76, 371
ketosis in, 188 Proelastase, 477 Propyl gallate, as antioxidant/food
Pregnenolone, 440f Proenzymes, 76 preservative, 119
in adrenal steroidogenesis, 438–440, Prostacyclins, 112
rapid response to physiologic demand clinical significance of, 196
440f, 441f and, 76 clotting/thrombosis affected by, 607, 607t
in testicular steroidogenesis, 442, 443f Prostaglandin E2, 112, 113f
Preinitiation complex, 343, 351–352 Profiling, protein-transcript, 412 Prostaglandin H synthase, 192
assembly of, 351–352 Progesterone, 439f, 440f Prostaglandins, 112, 113f, 190, 192
in protein synthesis, 365, 366f cyclooxygenase pathway in synthesis of,
Prekallikrein, 599f, 600 binding of, 455, 455t 192, 192–194, 193f, 194f
Premenstrual syndrome, vitamin B6 in receptors for, 471 Prostanoids, 112, 119
synthesis of, 438, 442, 445f clinical significance of, 196
management of, sensory Progesterone (∆4) pathway, 442, 443f cyclooxygenase pathway in synthesis of,
neuropathy and, 491 Progestin response element, 459t 192, 192–194, 193f, 194f
Prenatal diagnosis, recombinant DNA Progestins, binding of, 455 Prosthetic groups, 50
technology in, 409 Prohormones, 371 in catalysis, 50–51, 51f
Preprocollagen, 537 Proinsulin, 449, 450f Protamine, 603
Preprohormone, insulin synthesized as, 449, Prokaryotic gene expression. See also Gene Proteases/proteinases, 8, 477, 624t. See also
450f specific type
Preproparathyroid hormone (preproPTH), expression α2-macroglobulin binding of, 590
450, 451f eukaryotic gene expression compared in cartilage, 553
Preproprotein, albumin synthesized as, 583 as catalytically inactive proenzymes,
Preproteins, 498, 581 with, 391–395, 392t 76–77
Presequence. See Signal peptide as model for study, 375 mucin resistance to, 520
Preventive medicine, biochemical research unique features of, 375–376 of neutrophils, 623–624, 624t
affecting, 2 Prolactin, 437 in protein degradation, 242, 243f, 477
Primaquine-sensitive hemolytic anemia, 613 localization of gene for, 407t Staphylococcus aureus V8, for polypeptide
Primary structure, 21–29, 31. See also receptor for, 436 cleavage, 25, 26t
Protein sequencing Proline, 16t Protein 4.1, in red cell membranes, 615f,
amino acid sequence determining, 18–19 accumulation of (hyperprolinemia), 616f, 616t, 617
Edman reaction in determination of, 25, Protein C, in blood coagulation, 600t, 603
26f 249–250 Protein disulfide isomerase, protein folding
genomics in analysis of, 28 catabolism of, 249–250, 251f and, 37, 508
molecular biology in determination of, synthesis of, 238, 239f Protein-DNA interactions, bacteriophage
25–26 Proline dehydrogenase, block of proline lambda as paradigm for,
of polynucleotides, 291–292 378–383, 379f, 380f, 381f, 382f
catabolism at, 249–250
Proline hydroxylase, vitamin C as coenzyme

for, 496
Proline-cis,trans-isomerase, protein folding

and, 37, 37f
Prolyl hydroxylase reaction, 240, 240f, 535

682 / INDEX importins and exportins in, 501–503, loss of in trauma/infection, 480
502f in membranes, 419, 420t, 514. See also
Protein folding, 36–37, 37f
chaperones and, 499, 507–508, 508t KDEL amino acid sequence and, Glycoproteins; Membrane
after denaturation, 36 506–507, 508t proteins
ratio of to lipids, 416, 416f
Protein kinase A (PKA), 460, 462f membrane assembly and, 511–513, modular principals in construction of, 30
Protein kinase B (PKB), in insulin signal 512f, 512t monomeric, 34
phosphorylation of, 76, 77–79, 78f, 78t.
transmission, 465, 466f mitochondria in, 499–501, 501f See also Phosphorylation
Protein kinase C (PKC) peroxisomes/peroxisome disorders and, posttranslational modification of, 30,
37–39, 38f, 371
in calcium-dependent signal 503, 503t purification of, 21–24
transduction, 464, 464f protein destination and, 507, 507f, 508t receptors as, 431, 436
retrograde transport and, 507 soluble, 30
in platelet activation, 606f, 607 signal hypothesis of polyribosome binding structure of, 31–36
Protein kinase D1, in insulin signal diseases associated with disorders of,
and, 503–505, 504t, 505f 37
transmission, 466f, 467 signal sequences and, 492f, 498–499, folding and, 36–37, 37f
Protein kinase-phosphatase cascade, as higher orders of, 30–39
499f molecular modeling and, 36
second messenger, 437, 437t transport vesicles and, 508–511, 509t, nuclear magnetic resonance spec-
Protein kinases, 77 troscopy in analysis of, 35–36
510f primary, 21–29, 31. See also Primary
in cAMP-dependent signal transduction, Protein turnover, 74, 242 structure
460–461, 462f prion diseases associated with
membranes affecting, 511 alteration of, 37
in cGMP-dependent signal transduction, rate of enzyme degradation and, 74 quaternary, 33–35, 35f
463 Proteinases. See Proteases/proteinases secondary, 31, 31–33, 31f, 32f, 33f,
Proteins. See also specific type and Peptides 34f
deficiency of, 151–152 β-turns in, 32, 34f supersecondary motifs and, 33
DNA-dependent, in double-strand break acute phase, 583, 583t tertiary, 33–35, 35f
x-ray crystallography in analysis of, 35
repair, 338 negative, vitamin A as, 483–484 synthesis of, 358–373. See also Protein
in glycogen metabolism, 147–148, 149f, L-α-amino acids in, 14 sorting
asymmetry of, membrane assembly and, amino acids in, 124, 124f
151, 151f elongation in, 367–370, 368f
in hormonal regulation, 436, 465–468 511, 512f environmental threats affecting, 370
binding, 454–455, 454t, 455t in fed state, 232
of lipolysis, 215, 216f catabolism of, 242–248 genetic code/RNA and, 307–308,
in initiation of protein synthesis, 365 classification of, 30 309t, 358–363. See also Genetic
in insulin signal transmission, 465–467, configuration of, 30 code
conformation of, 30 inhibition of by antibiotics, 371–372,
466f 372f
in Jak/STAT pathway, 467, 467f peptide bonds affecting, 20 initiation of, 365–367, 366f, 367f
in NF-κB pathway, 468, 468f core, 542, 543f by mitochondria, 499–501, 501t
in protein phosphorylation, 77, 78f modular principles in, 30
Protein-lipid respiratory chain complexes, in glycosaminoglycan synthesis, polysomes in, 370, 498, 499f
542–543 posttranslational processing and, 371
93 in ribosomes, 126, 127f
Protein-losing gastroenteropathy, 582 degradation of, to amino acids, 242, 243f recognition and attachment (charging)
Protein phosphatase-1, 147, 148, 149f, 151, denaturation of in, 360, 360f
recombinant DNA techniques for,
151f protein refolding and, 36 407
Protein phosphatases, 77. See also temperature and, 63 reticulocytes in, 611
dietary termination of, 369f, 370
Phosphatases digestion and absorption of, 477 translocation and, 368
Protein profiling, 412 metabolism of, in fed state, 232 viruses affecting, 370–371, 371f
Protein-RNA complexes, in initiation, requirements for, 479–480 transmembrane
dimeric, 34 ion channels as, 423–424, 425f, 426t
365–367, 366f domains of, 33–34 in red cells, 615–616, 615f, 616f,
Protein S, in blood coagulation, 600t, 603 encoding of by human genome, 636, 616t
Protein sequencing
637t
Edman reaction in, 25, 26f in extracellular and intracellular fluid,
genomics and, 28
mass spectrometry in, 27, 27f, 27t 416, 416t
molecular biology in, 25–26 fibrous, 30
peptide purification for, 21–24
polypeptide cleavage and, 25, 26t collagen as, 38
proteomics and, 28–29 function of, bioinformatics in
purification for, 21–24, 22f, 23f, 24f,
identification of, 28–29
25f fusion, in enzyme study, 58, 59f
Sanger’s method of, 24–25 globular, 30
Protein sorting, 498–513 Golgi apparatus in glycosylation and
chaperones and, 507–508, 508t
cotranslational insertion and, 505–506, sorting of, 509
import of, by mitochondria, 499–501,
506f
disorders due to mutations in genes 501t

encoding, 512t, 513
Golgi apparatus in, 498, 500f, 507, 509

transport, 454–455, 454t, 455t “Puffs,” polytene chromosome, 318, 318f INDEX / 683
xenobiotic cell injury and, 631 Pulsed-field gel electrophoresis, for gene
Proteoglycans, 109, 535, 538, 542–549, oxidation of, 134, 135f, 140–142, 141f,
isolation, 635t 142f, 143t. See also Acetyl-CoA;
542f. See also Pumps, 415 Glycolysis
Glycosaminoglycans
in bone, 548t in active transport, 427–428, 428f clinical aspects of, 142–143
carbohydrates in, 542, 542f, 543f Purification, protein/peptide, 21–24 enzymes in, 156t
in cartilage, 551, 553 Purine nucleoside phosphorylase deficiency, gluconeogenesis and, 153, 154f
disease associations and, 548–549 Pyruvate carboxylase, 133, 134f, 156t
functions of, 547–549, 548t 300 in gluconeogenesis regulation, 133, 134f,
galactose in synthesis of, 167–169, 170f Purines/purine nucleotides, 286–290, 286f,
link trisaccharide in, 518 153, 156t
Proteolysis 289f Pyruvate dehydrogenase, 134, 135f, 140,
in covalent modification, 76, 76–77, 77f dietarily nonessential, 293
in prochymotrypsin activation, 77, 77f metabolism of, 293–302 141f, 156t
Proteome/proteomics, 28–29, 414, deficiency of, 143
636–637, 637–638 disorders of, 300 regulation of, 141–142, 142f
Prothrombin (factor II), 600t, 601, 602f gout as, 299
activation of, 601 acyl-CoA in, 141–142, 142f, 178
coumarin drugs affecting, 487, 604 uric acid formation and, 299, 299f thiamin diphosphate as coenzyme for,
in vitamin K deficiency, 487 synthesis of, 293–294, 294f, 295f, 296f,
Prothrombinase complex, 601 488
Proton acceptors, bases as, 9 297f Pyruvate dehydrogenase complex, 140
Proton donors, acids as, 9 catalysts in, 293, 294f Pyruvate kinase, 156t
Proton pump, respiratory chain complexes pyrimidine synthesis coordinated with,
as, 96, 96f, 97f deficiency of, 143, 619
Proton-translocating transhydrogenase, as 299 gluconeogenesis regulation and, 157
source of intramitochondrial “salvage” reactions in, 294, 295f, 297f in glycolysis, 137–139, 138f, 156t
NADPH, 99 ultraviolet light absorbed by, 290
Protons, transport of, by hemoglobin, 44, Puromycin, 372, 372f regulation and, 140
45f Putrescine, in polyamine synthesis, 266f
Protoporphyrin, 270, 272f Pyranose ring structures, 103f, 104 Q (coenzyme Q/ubiquinone), 92, 95f
incorporation of iron into, 271–272, 272f Pyridoxal phosphate, 50, 491, 491f Q10 (temperature coefficient), enzyme-
Protoporphyrin III, 271, 276f in heme synthesis, 270
Protoporphyrinogen III, 271, 276f in urea biosynthesis, 243 catalyzed reactions and, 63
Protoporphyrinogen oxidase, 271, 275f, 276f Pyridoxine/pyridoxal/pyridoxamine QT interval, congenitally long, 432t
Provitamin A carotenoids, 482–483 Quaternary structure, 33–35, 35f
Proximal histidine (histidine F8) (vitamin B6), 482t, 491, 491f
in oxygen binding, 40, 41f deficiency of, 482t, 491 of hemoglobins, allosteric properties and,
replacement of in hemoglobin M, 46 42–46
Proximity, catalysis by, 51 xanthurenate excretion in, 258, 258f
PrP (prion-related protein), 37 excess/toxicity of, 491 stabilizing factors and, 35
PRPP Pyrimethamine, 494
in purine synthesis, 294, 295f Pyrimidine analogs, in pyrimidine R groups, amino acid properties affected by,
in pyrimidine synthesis, 296, 298f, 299 18, 18t
PRPP glutamyl amidotransferase, 294, 295f nucleotide biosynthesis, 297
PRPP synthetase, defect in, gout caused by, Pyrimidines/pyrimidine nucleotides, pK/pKa, 18
299 R (relaxed) state, of hemoglobin,
Pseudo-Hurler polydystrophy, 532, 546t, 286–290, 286f, 289f
547 dietarily nonessential, 293 oxygenation and, 43, 43f, 44f
Pseudogenes, 325, 414 metabolism of, 293–302, 301f Rab protein family, 511
Psi (ψ) angle, 31, 31f RAC3 coactivator, 472, 472t
PstI, 399t diseases caused by catabolite Radiation, nucleotide excision-repair of
PstI site, insertion of DNA at, 402, 403f overproduction and, 300–301
PTA. See Plasma thromboplastin antecedent DNA damage caused by, 337
PTC. See Plasma thromboplastin water-soluble metabolites and, 300, Radiation hybrid mapping, 635t
component 301f Ran protein, 501, 502f, 503
Pteroylglutamic acid. See Folic acid Rancidity, peroxidation causing, 118
PTH. See Parathyroid hormone precursors of, deficiency of, 300–301 Rapamycin, mammalian target of (mTOR),
PTSs. See Peroxisomal-matrix targeting synthesis of, 296–299, 298f
sequences in insulin signal transmission,
catalysts in, 296 466f, 467
purine synthesis coordinated with, 299 RAR. See Retinoic acid receptor
regulation of, 297–299, 298f RARE. See Retinoic acid response element
ultraviolet light absorbed by, 290 Rate constant, 62
Pyrophosphatase, inorganic Keq as ratio of, 62–63
in fatty acid activation, 85, 180 Rate of degradation (kdeg), control of, 74
in glycogen biosynthesis, 145, 146f Rate-limiting reaction, metabolism egulated
Pyrophosphate by, 73
free energy of hydrolysis of, 82t Rate of synthesis (ks), control of, 74
inorganic, 85, 85f Rb protein. See Retinoblastoma protein
Pyrrole, 40, 41f Reactant concentration, chemical reaction
Pyruvate, 123 rate affected by, 62
formation of, in amino acid carbon Reactive oxygen species. See Free radicals

skeleton catabolism, 250–255,
252f, 253f

684 / INDEX Redox state, 184 collection and oxidation of reducing
Reduced porphyrins, 272 equivalents and, 92–93, 93f, 94f,
Rearrangements, DNA Reducing equivalents 95f
in antibody diversity, 325–326, 393,
593–594 in citric acid cycle, 130–133, 132f dehydrogenases in, 87
recombinant DNA technology in in pentose phosphate pathway, 166 energy for metabolism provided by,
detection of, 409, 409t respiratory chain in collection and oxida-
93–95, 98f
recA, 381, 382f tion of, 92–93, 93f, 94f, 95f oxidative phosphorylation at level of, 94
Receptor-associated coactivator 3 (RAC3 5α-Reductase, 442, 444f poisons affecting, 92, 95, 96f
Reduction, definition of, 86 as proton pump, 96, 96f, 97f
coactivator), 472, 472t Reductive activation, of molecular oxygen, redox potential of components of,
Receptor-effector coupling, 435–436
Receptor-mediated endocytosis, 429f, 627 92–93, 94f, 95f
Refsum’s disease, 188, 503, 503t substrates for, citric acid cycle providing,
430 Regional asymmetries, membrane, 420
Receptors, 431, 436. See also specific type Regulated secretion, 498 131,131f
Regulatory proteins, binding of to DNA, Respiratory control, 81, 94–95, 97, 97t,
activation of in signal generation,
456–457, 458f motifs for, 387–390, 388t, 389f, 98f, 134–135
390f, 391f Respiratory distress syndrome, surfactant
nuclear, 436, 469, 469–471, 471f, 472t Regurgitation hyperbilirubinemia, 282
Recognition domains, on hormone Relaxation phase deficiency causing, 115, 202
of skeletal muscle contraction, 561, 564 Restriction endonucleases/enzymes, 312,
receptors, 435 of smooth muscle contraction
Recombinant DNA/recombinant DNA calcium in, 571 397–399, 399t, 400f, 414
nitric oxide in, 571–573, 573f in recombinant DNA technology,
technology, 396–414, 635t Relaxed (R) state, of hemoglobin,
base pairing and, 396–397 oxygenation and, 43, 43f, 44f 399–400, 399t, 400f, 400t, 401f
blotting techniques in, 403, 404f Releasing factors (RF1/RF3), in protein Restriction enzymes. See Restriction
chimeric molecules in, 397–406 synthesis termination, 369f, 370
cloning in, 400–402, 401f, 402t, 403f Remnant removal disease, 228t endonucleases
definition of, 414 Renal glomerulus, laminin in basal lamina Restriction fragment length polymorphisms
DNA ligase in, 399–400 of, 540–542
DNA sequencing in, 404, 405f Renal threshold for glucose, 161 (RFLPs), 57, 409–411, 411f
double helix structure and, 396, 397 Renaturation, DNA, base pair matching in forensic medicine, 411
in enzyme study, 58, 59f and, 305–306 Restriction map, 399
gene mapping and, 406–407, 407t Renin, 451, 452f Retention hyperbilirubinemia, 282
in genetic disease diagnosis, 407–412, Renin-angiotensin system, 451–452, 452f Reticulocytes, in protein synthesis, 611
Repeat sequences, 637 Retina
408f, 409t, 410f, 411f amino acid, 519, 520f gyrate atrophy of, 250
hybridization techniques in, 403–404 short interspersed (SINEs), 321–322, retinaldehyde in, 483, 484f
libraries and, 402 414 Retinal. See also Retinol
oligonucleotide synthesis in, 404–405 Repetitive-sequence DNA, 320, 321–322 Retinaldehyde, 482, 483f
organization of DNA into genes and, Replication/synthesis. See DNA, Retinitis pigmentosa, essential fatty acid
replication/synthesis of;
397, 398f, 399t RNA, synthesis of deficiency and, 192
polymerase chain reaction in, 405–406, Replication bubbles, 331–333, 331f, 332f, Retinoblastoma protein, 333
333f Retinoic acid, 482, 483f. See also Retinol
406f Replication fork, 327–328, 327f
practical applications of, 406–412 Reporter genes, 385–386, 387f, 388f functions of, 483
restriction enzymes and, 397–400, 399t, Repression, enzyme receptors for, 471, 483
enzyme synthesis control and, 74 Retinoic acid receptor (RAR), 471, 483
400f, 400t, 401f in gluconeogenesis regulation, 155–157 Retinoic acid response element, 459t
terminology used in, 413–414 Repressor protein/gene, lambda (cI), Retinoid X receptor (RXR), 470, 470f, 471,
transcription and, 397, 398f 379–383, 380f, 381f, 382f
Recombinant erythropoietin (epoetin Repressors, 348 483
in gene expression, 374, 377, 378, 385 Retinoids, 482–484, 483f, 484f. See also
alfa/EPO), 526, 610 tissue-specific expression and, 385
Recombinant fusion proteins, in enzyme Reproduction, prostaglandins in, 190 Retinol
Respiration, 86 Retinol, 482, 482t, 483f, 484f. See also
study, 58, 59f Respiratory burst, 479, 622–623
Recombination, chromosomal, 323–324, Respiratory chain, 92–101. See also Vitamin A
Oxidative phosphorylation deficiency of, 482t
323f, 324f clinical aspects of, 100–101 functions of, 482t, 483, 484f
Recruitment hypothesis, of preinitiation Retinol-binding protein, 583t
Retrograde transport, 505, 510
complex formation, 352 from Golgi apparatus, 507
Red blood cells, 609–610, 610–619. See Retroposons/retrotransposons, 321, 637
Retroviruses, reverse transcriptases in, 308,
also Erythrocytes
recombinant DNA technology in study 332–333
Reverse cholesterol transport, 210, 211f,
of, 624
Red thrombus, 598 219, 224
Red (slow) twitch fibers, 574–576, 575t Reverse transcriptase/reverse transcription,
Redox (oxidation-reduction) potential, 86,
308, 333, 414
87t in recombinant DNA technology, 400t
of respiratory chain components, 92–93,

94f, 95f