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

Reversed-phase high-pressure classes/species of, 307–308, 309t, 341, INDEX / 685
chromatography, for protein/ 342t
peptide purification, 23–24 RNA polymerases, DNA-dependent, in
complementarity of, 306, 309f RNA synthesis, 342–343, 342f,
Reversible covalent modifications, 77–79, heterogeneous nuclear (hnRNA), 310 343t
78f, 78t. See also Phosphorylation
gene regulation and, 354 RNA primer, in DNA synthesis, 328, 329f,
Reye’s syndrome, orotic aciduria in, 300 messenger (mRNA), 307, 309–310, 330f
RFLPs. See Restriction fragment length
310f, 311f, 341, 342t, 359 RNA probes, 402, 414
polymorphisms alternative splicing and, 354, 354f, RNAP. See RNA polymerases
RFs. See Releasing factors RNase. See Ribonucleases
Rheumatoid arthritis, glycosylation 393–394, 636 ROS (reactive oxygen species). See Free
codon assignments in, 358, 359t
alterations in, 533 editing of, 356 radicals
Rho-dependent termination signals, 344, expression of, detection of in gene Rotor syndrome, 283
Rough endoplasmic reticulum
346, 346f isolation, 635t
Rhodopsin, 483, 484f modification of, 355–356 glycosylation in, 524–525, 525f
Riboflavin (vitamin B2), 86, 482t, 489–490 nucleotide sequence of, 358 in protein sorting, 498, 499f, 500f
protein synthesis and, 370
in citric acid cycle, 133 mutations caused by changes in, routes of protein insertion into,
coenzymes derived from, 50–51, 489, 490 361–363, 361f, 362f, 364f
deficiency of, 482t, 490 505–507, 506f
dehydrogenases dependent on, 87 polycistronic, 376 signal hypothesis of polyribosome
Ribonucleases, 312 recombinant DNA technology and,
Ribonucleic acid. See RNA binding to, 503–505, 504t, 505f
Ribonucleoside diphosphates (NDPs), 397 rRNA. See Ribosomal RNA
relationship of to chromosomal DNA, RT-PCR, 414
reduction of, 294, 297f RXR. See Retinoid X receptor
Ribonucleosides, 286, 287f 321f Ryanodine, 563
Ribonucleotide reductase complex, 294, stability of, regulation of gene Ryanodine receptor, 563, 564f

297f expression and, 394–395, 394f mutations in gene for, diseases caused by,
Ribose, 102 transcription starting point and, 564–565, 565f, 630t
342
in nucleosides, 286, 287f variations in size/complexity of, 397, RYR. See Ryanodine receptor
pentose phosphate pathway in
399t S50, 67
production of, 123, 163, 166 modification of, 355–356 S phase of cell cycle, DNA synthesis during,
D-Ribose, 104f, 105t, 286 processing of, 352–355
Ribose phosphate, pentose phosphate path- 333–335, 334f, 335t
alternative, in regulation of gene Saccharopine, in lysine catabolism, 256f,
way in production of, 163, expression, 354, 355f, 393–394
164f 258
Ribose 5-phosphate, in purine synthesis, in protein synthesis, 307–308, 309t Salt (electrostatic) bonds (salt bridges/
293–294, 295f ribosomal (rRNA), 307–308, 310–311,
Ribose 5-phosphate ketoisomerase, 163, linkages), 7
165f 341, 342t oxygen binding rupturing, Bohr effect
Ribosomal dissociation, in protein as peptidyltransferase, 368, 370t
synthesis, 365, 366f processing of, 355 protons and, 44–45, 45f
Ribosomal RNA (rRNA), 307–308, small nuclear (snRNA), 308, 309t, 311, “Salvage” reactions
310–311, 341, 342t. See also
RNA 341, 342t, 414 in purine synthesis, 294, 295f, 297f
as peptidyltransferase, 368, 370t small stable, 311 in pyrimidine synthesis, 296
processing of, 355 splicing, 352–354, 414 Sanfilippo syndrome, 546t
Ribosomes, 310, 312t Sanger’s method
bacterial, 371–372 alternative, in regulation of gene for DNA sequencing, 404, 405f
protein synthesis in, 126, 127f expression, 354, 354f, for polypeptide sequencing, 24–25
dissociation and, 370 393–394, 636 Sanger’s reagent (1-fluoro-2,4-dinitro-
Ribozymes, 308, 311, 356
D-Ribulose, 105t, 106f recombinant DNA technology and, benzene), for polypeptide
Ribulose 5-phosphate 3-epimerase, 163, 397, 398f sequencing, 25
165f Sarcolemma, 556
Richner-Hanart syndrome, 255 structure of, 306–312, 308f, 309f, 311f, Sarcomere, 556–557, 557f
Ricin, 372, 518t 312f Sarcoplasm, 556
Rickets, 482t, 484, 551t of cardiac muscle, 566
Right operator, 379–383, 380f, 382f synthesis of, 341–352 Sarcoplasmic reticulum, calcium level in
Rigor mortis, 562, 564 initiation/elongation/termination in, skeletal muscle and, 563–564,
RNA, 303, 306–312, 341–357 342, 342f, 343–344, 344f 563f, 564f
as catalyst, 356 Saturated fatty acids, 111, 112, 112t
in chromatin, 314 transfer (tRNA), 308, 310, 312f, 341, in membranes, 417, 418f
342t, 360–361, 361f Saturation kinetics, 64f, 66
sigmoid substrate, Hill equation in
aminoacyl, in protein synthesis, 368 evaluation of, 66–67, 67f
anticodon region of, 359 Scavenger receptor B1, 210, 211f
processing and modification of, 355,

356
suppressor, 363
xenobiotic cell injury and, 631
RNA editing, 356
RNA polymerase III, 343t

686 / INDEX in glycine synthesis, 238, 239f Signal hypothesis, of polyribosome binding,
phosphorylated, 264 503–505, 504t, 505f
Scheie syndrome, 546t synthesis of, 238, 238f
Schindler disease, 532–533, 533t tetrahydrofolate and, 492–494, 493f Signal peptidase, 504, 505f
Scrapie, 37 Serine 195, in covalent catalysis, 53–54, 54f Signal peptide, 498, 503–504, 508t
Scurvy, 482t, 496 Serine hydroxymethyltransferase, 250, 252f,
albumin, 583
collagen affected in, 38–39, 496, 493–494 in protein sorting, 498–499, 499f, 500f,
538–539 Serine protease inhibitor, 589. See also
503–504, 505, 505f
SDS-PAGE. See Sodium dodecyl α1-Antiproteinase Signal recognition particle, 504
sulfate-polyacrylamide gel Serine proteases. See also specific type Signal sequence. See Signal peptide
electrophoresis Signal transducers and activators of
conserved residues and, 54, 55t
Se gene, 618 in covalent catalysis, 53–54, 54f transcription (STATs), 467, 467f
Sec1 proteins, 511 zymogens of, in blood coagulation, 600, Signal transduction, 456–473
Sec61p complex, 504
Second messengers, 76, 436–437, 437t, 600t, 601 GPI-anchors in, 528
Serotonin, 266–267, 621t hormone response to stimulus and, 456,
457–468, 461t, 463t. See also Serpin, 589. See also α1-Antiproteinase
specific type Serum prothrombin conversion accelerator 457f
calcium as, 436–437, 437t, 457 intracellular messengers in, 457–468,
cAMP as, 147, 436, 437t, 457, 458–462, (SPCA/factor VII), 599f, 600t,
460t, 462f 601 461t, 463t. See also specific type
cGMP as, 290, 436, 437t, 457, 462–463 coumarin drugs affecting, 604 in platelet activation, 606, 606f
diacylglycerol as, 464, 465f Sex (gender), xenobiotic-metabolizing signal generation and, 456–457, 458f,
inositol trisphosphate as, 464–465, 464f, enzymes affected by, 630
465f Sex hormone-binding globulin 459f, 459t
precursors of (testosterone-estrogen-binding transcription modulation and, 468–473,
phosphatidylinositol as, 115, 115f globulin), 455, 455t, 583t
phospholipids as, 197 SGLT 1 transporter protein, 475, 475f 470f, 471f, 472t
Secondary structure, 31, 31–33, 32f, 33f, SGOT. See Aspartate aminotransferase Silencers, 348
34f SGPT. See Alanine aminotransferase
peptide bonds affecting, 31, 31f SH2 domains. See Src homology 2 (SH2) recombinant DNA technology and, 397
supersecondary motifs and, 33 domains Silencing mediator for RXR and TR
Secretor (Se) gene, 618 SHBG. See Sex hormone-binding globulin
Secretory component, of IgA, 595f Short interspersed repeat sequences (SMRT), 472t, 473
Secretory granules, protein entry into, 507, (SINEs), 321–322, 414 Silent mutations, 361
507f Shoshin beriberi, 489 Silicon, 496t
Secretory (exocytotic) pathway, 498 Shotgun sequencing, 634 Simple diffusion, 423, 423t, 424f
Secretory vesicles, 498, 500f SI nuclease, in recombinant DNA Simvastatin, 229
D-Sedoheptulose, 106f technology, 400t SINEs. See Short interspersed repeat
Selectins, 528–530, 529f, 529t, 530f Sialic acids, 110, 110f, 116, 169, 171f
Selectivity/selective permeability, in gangliosides, 171f, 201, 203f sequences
membrane, 415, 423–426, in glycoproteins, 109t, 516t Single displacement reactions, 69, 69f
423t, 424f, 425f, 426t Sialidosis, 532–533, 533t, 546, 546t Single nucleotide polymorphism (SNP), 414
Selenium, 496t Sialoprotein, bone, 548t, 550 Single-pass membrane proteins,
in glutathione peroxidase, 88, 166 Sialyl-LewisX, selectins binding, 530, 530f
Selenocysteine, synthesis of, 240, 240f Sialylated oligosaccharides, selectins glycophorins as, 615–616,
Selenophosphate synthetase/synthase, 240, binding, 530 615f, 616f, 616t
240f Sickle cell disease, 363, 619 Single-stranded DNA, replication from,
Self-assembly pedigree analysis of, 409, 410f 326. See also DNA,
in collagen synthesis, 537 recombinant DNA technology in replication/synthesis of
of lipid bilayer, 418 detection of, 408–409 Single-stranded DNA-binding proteins
Self-association, hydrophobic interactions Side chain cleavage enzyme P450 (SSBs), 326, 327, 327f, 328t
and, 6–7 (P450scc), 438, 440f, 442 Sister chromatid exchanges, 325, 325f
Sensory neuropathy, in vitamin B6 excess, Side chains, in porphyrins, 270, 271f Sister chromatids, 318, 319f
491 Sigmoid substrate saturation kinetics, Hill Site-directed mutagenesis, in enzyme study,
Sepharose-lectin column chromatography, equation in evaluation of, 66–67, 58
in glycoprotein analysis, 515t 67f Site-specific DNA methylases, 398
Sequential displacement reactions, 69, 69f Signal. See also Signal peptide Site specific integration, 324
Serine, 15t generation of, 456–457, 458f, 459f, 459t Sitosterol, for hypercholesterolemia, 229
catabolism of, pyruvate formation and, in recombinant DNA technology, 414 Size exclusion chromatography, for
250, 252f transmission of. See also Signal protein/peptide purification,
conserved residues and, 54, 55t transduction 21–22, 23f
in cysteine and homoserine synthesis, across membrane, 415, 431 SK. See Streptokinase
239, 239f Skeletal muscle, 556, 568t. See also Muscle;
Muscle contraction
glycogen stores in, 573
metabolism in, 125, 125f
lactate production and, 139
as protein reserve, 576
slow (red) and fast (white) twitch fibers
in, 574–576, 575t

Skin Sodium-potassium pump (Na+-K+ ATPase), INDEX / 687
essential fatty acid deficiency affecting, 427–428, 428f
194–195 SR-B1. See Scavenger receptor B1
mutant keratins and, 578 in glucose transport, 428, 429f SRC-1 coactivator, 472, 472t
vitamin D3 synthesis in, 445, 446f, 484, Solubility point, of amino acids, 18 Src homology 2 (SH2) domains
485f Soluble NSF attachment factor (SNAP)
in insulin signal transmission, 465, 466f,
Sleep, prostaglandins in, 190 proteins, 509, 510f, 511 467
Sliding filament cross-bridge model, of Solutions, aqueous, Kw of, 9
Solvent, water as, 5, 6f in Jak/STAT pathway, 467, 467f
muscle contraction, 557–559, Sorbitol, in diabetic cataract, 172 SRP. See Signal recognition particle
558f Sorbitol dehydrogenase, 167, 169f SRS-A. See Slow-reacting substance of
Slow acetylators, 630 Sorbitol intolerance, 172
Slow-reacting substance of anaphylaxis, 196 Sorbitol (polyol) pathway, 172 anaphylaxis
Slow (red) twitch fibers, 574–576, 575t Soret band, 273 ssDNA. See Single-stranded DNA
Sly syndrome, 546t Southern blot transfer procedure, 305–306, Staphylococcus aureus V8 protease, for
Small intestine
cytochrome P450 isoforms in, 627 403, 404f, 414 polypeptide cleavage, 25, 26t
monosaccharide digestion in, 475, 475f Southwestern blot transfer procedure, 403, STAR. See Steroidogenic acute regulatory
Small nuclear RNA (snRNA), 308, 309t,
311, 341, 342t, 414 414 protein
Small nucleoprotein complex (snurp), 353 SPARC (bone) protein, 548t Starch, 107, 108f
Small stable RNA, 311 Sparteine, CYP2D6 in metabolism of,
Smoking glycemic index of, 474
CYP2A6 metabolism of nicotine and, 628 hydrolysis of, 474
628 SPCA. See Serum prothrombin conversion Starling forces, 580
cytochrome P450 induction and, 628 Starvation, 80
nucleotide excision-repair of DNA accelerator clinical aspects of, 236
damage caused by, 337 Specific acid/base catalysis, 51–52 fatty liver and, 212
Smooth endoplasmic reticulum, cy- Specificity, enzyme, 49, 50f ketosis in, 188
tochrome P450 isoforms in, Spectrin, 615, 615f, 616f, 616t, 617 metabolic fuel mobilization in, 232–234,
627
Smooth muscle, 556, 568t abnormalities of, 617 234f, 234t
actin-myosin interactions in, 572t Spectrometry triacylglycerol redirection and, 208
contraction of Statin drugs, 229
calcium in, 570–571, 571f covalent modifications detected by, 27, STATs (signal transducers and activators of
myosin-based regulation of, 570 27f, 27t
myosin light chain phosphorylation in, transcription), 467, 467f
570 for glycoprotein analysis, 514, 515t Stearic acid, 112t
relaxation of Spectrophotometry Steely hair disease (Menkes disease), 588
calcium in, 571 Stem cells, differentiation of to red blood
nitric oxide in, 571–573, 573f for NAD(P)+-dependent dehydrogenases,
SMRT, 472t, 473 56, 56f cells, erythropoietin in regulation
SNAP (soluble NSF attachment factor) of, 610, 611f
proteins, 509, 510f for porphyrins, 273–274 Stereochemical (-sn-) numbering system,
SNAP 25, 511 Spectroscopy, nuclear magnetic resonance 114, 115f
SNARE proteins, 509, 510f, 511 Stereoisomers. See also Isomerism
SNAREpins, 511 (NMR) of steroids, 117, 118f
SNP. See Single nucleotide polymorphism for glycoprotein analysis, 514, 515f Steroid nucleus, 117, 117f, 118f
snRNA. See Small nuclear RNA protein structure demonstrated by, Steroid receptor coactivator 1 (SRC-1
Snurp (small nucleoprotein [snRNP] coactivator), 472, 472t
complex), 353 35–36 Steroid sulfates, 201
Sodium, 496t Spermidine, synthesis of, 265–266, 266f Steroidogenesis. See Steroids, synthesis of
in extracellular and intracellular fluid, Spermine, synthesis of, 265–266, 266f Steroidogenic acute regulatory protein
416, 416t Spherocytosis, hereditary, 432t, 617, 617f (STAR), 442
permeability coefficient of, 419f Sphingolipidoses, 202–203, 203t Steroids, 117–118, 117f, 118f, 119f. See
Sodium-calcium exchanger, 463 Sphingolipids, 197 also specific type
Sodium dodecyl sulfate-polyacrylamide gel adrenal. See also Glucocorticoids;
electrophoresis metabolism of, 201–202, 202f, 203f Mineralocorticoids
for protein/peptide purification, 24, 24f, clinical aspects of, 202–203, 203t synthesis of, 438–442, 440f, 441f
25f calcitriol as, 484
red cell membrane proteins determined in multiple sclerosis, 202 receptors for, 436
by, 614–615, 615f Sphingomyelins, 116, 116f, 201, 202f stereoisomers of, 117, 118f
storage/secretion of, 453, 454t
in membranes, 417 synthesis of, 123f, 124, 438, 438–445,
membrane asymmetry and, 420 439t, 440f, 441f
transport of, 454–455, 455t
Sphingophospholipids, 111 vitamin D as, 484
Sphingosine, 116, 116f Sterol 27-hydroxylase, 226
Spina bifida, folic acid supplements in Sterols, 117
in membranes, 417
prevention of, 494 Stickler syndrome, 553
Spliceosome, 353, 414
Spongiform encephalopathies, transmissible

(prion diseases), 37
Squalene, synthesis of, in cholesterol

synthesis, 219, 221f, 222f
Squalene epoxidase, in cholesterol synthesis,

220, 222f

688 / INDEX Sucrose, 106–107, 107f, 107t t-SNARE proteins, 509, 511
glycemic index of, 474 T (taut) state, of hemoglobin
Sticky end ligation/sticky-ended DNA, 299,
398, 400f, 401f, 414 Sugars. See also Carbohydrates 2,3-bisphosphoglycerate stabilizing, 45,
amino (hexosamines), 106, 106f 45f
“Sticky foot,” 527 glucose as precursor of, 169, 171f
“Sticky patch,” in hemoglobin S, 46, 46f in glycosaminoglycans, 109, 169, 171f oxygenation and, 43, 43f, 44f
Stoichiometry, 60 in glycosphingolipids, 169, 171f T tubular system, in cardiac muscle, 566
Stokes radius, in size exclusion interrelationships in metabolism of, T-type calcium channel, 567
171f TAFs. See TBP-associated factors
chromatography, 21 classification of, 102, 102t Talin, 540, 541f
Stop codon, 369f, 370 deoxy, 106, 106f Tandem, 414
Stop-transfer signal, 506 “invert,” 107 Tandem mass spectrometry, 27
Strain, catalysis by, 52 isomerism of, 102–104, 103f Tangier disease, 228t
Streptokinase, 605, 605f, 606t nucleotide, in glycoprotein biosynthesis, TaqI, 399t
Streptomycin, 106 516–517, 516t Target cells, 434–435, 435t
Striated muscle, 556, 557, 557f. See also
“Suicide enzyme,” cyclooxygenase as, 194 receptors for, 435, 436f
Cardiac muscle; Skeletal muscle Sulfate Targeted gene disruption/knockout, 412
actin-myosin interactions in, 572t Tarui’s disease, 152t
Stroke, with mitochondrial encephalopathy active (adenosine 3′-phosphate-5′- TATA binding protein, 346, 349f, 350,
phosphosulfate), 289, 289f, 629
and lactic acidosis (MELAS), 351
100–101 in glycoproteins, 515 TATA box, in transcription control, 345,
Strong acids, 9 in mucins, 520
Strong bases, 9 Sulfatide, 116 345f, 346, 347f, 348, 348f, 351t
Structural proteins, 535 Sulfation, of xenobiotics, 629 Taurochenodeoxycholic acid, synthesis of,
Stuart-Prower factor (factor X), 599f, 600, Sulfo(galacto)-glycerolipids, 201
600t Sulfogalactosylceramide, 201 226f
activation of, 599–600, 599f accumulation of, 203 Taut (T) state, of hemoglobin
coumarin drugs affecting, 604 Sulfonamides, hemolytic anemia
Substrate analogs, competitive inhibition 2,3-bisphosphoglycerate stabilizing, 45,
by, 67–68, 67f precipitated by, 613 45f
Substrate level, phosphorylation at, 94 Sulfonylurea drugs, 188
Substrate shuttles Sulfotransferases, in glycosaminoglycan oxygenation and, 43, 43f, 44f
coenzymes as, 50 Tay-Sachs disease, 203t
in extramitochondrial NADH oxidation, synthesis, 543 TBG. See Thyroxine-binding globulin
99, 100f Sunlight. See Ultraviolet light TBP. See TATA binding protein
Substrate specificity, of cytochrome P450 Supercoils, DNA, 306, 332, 333f TBP-associated factors, 346, 350, 351
isoforms, 627 Superoxide anion free radical, 90–91, TΨC arm, of tRNA, 310, 312f, 360, 361f
Substrates, 49 TEBG. See Testosterone-estrogen-binding
competitive inhibitors resembling, 611–613, 613t. See also Free
67–68, 67f radicals globulin
concentration of, enzyme-catalyzed production of in respiratory burst, 622 Telomerase, 318
reaction rate affected by, 64, Superoxide dismutase, 90–91, 119, Telomeres, 318, 319f
64f, 65f 611–613, 613t, 622 Temperature
Hill model of, 66–67, 67f Supersecondary structures, 33
Michaelis-Menten model of, 65–66, Suppressor mutations, 363 chemical reaction rate affected by, 62,
66f Suppressor tRNA, 363 62f
conformational changes in enzymes Surfactant, 115, 197
caused by, 52, 53f deficiency of, 115, 202 enzyme-catalyzed reaction rate affected
multiple, 69–70 SV40 viruses, cancer caused by by, 63
Succinate, 131–133, 132f Swainsonine, 527, 527t
Succinate dehydrogenase, 87, 132f, Symport systems, 426, 426f in fluid mosaic model of membrane
133 Syn conformers, 287, 287f structure, 422
inhibition of, 67–68, 67f Synaptobrevin, 511
Succinate semialdehyde, 267, 268f Syntaxin, 511 Temperature coefficient (Q10), enzyme-
Succinate thiokinase (succinyl-CoA Synthesis, rate of (ks), control of, 74 catalyzed reactions and, 63
synthetase), 131, 132f
Succinic acid, pK/pKa value of, 12t t1/2. See Half life Template binding, in transcription, 342,
Succinyl-CoA, in heme synthesis, 270–273, T3. See Triiodothyronine 342f
273f, 274f, 275f, 276f T4. See Thyroxine
Succinyl-CoA-acetoacetate-CoA transferase Tm. See Melting temperature/transition Template strand DNA, 304, 306, 307f
(thiophorase), 133, 186, 186f transcription of in RNA synthesis,
Succinyl-CoA synthetase (succinate temperature 341–343, 342f
thiokinase), 131, 132f T lymphocytes, 591
Sucrase-isomaltase complex, 475 t-PA. See Tissue plasminogen activator Tenase complex, 600–601
TΨC arm, of tRNA, 310, 312f, 360, 361f Terminal transferase, 400t, 414
Termination

chain
in glycosaminoglycan synthesis, 543
in transcription cycle, 342, 342f

of protein synthesis, 369f, 370
of RNA synthesis, 342, 342f, 344, 344f
Termination signals, 359
for bacterial transcription, 346, 346f
for eukaryotic transcription, 349–350

Tertiary structure, 33–35, 35f Thiamin triphosphate, 489 INDEX / 689
stabilizing factors and, 35 Thick (myosin) filaments, 557, 558f
Thin (actin) filaments, 557, 558f, 559f Thyroglobulin, 447, 449
Testes, hormones produced by, 437, 442, Thioesterase, 173 Thyroid-binding globulin, 454, 583t
443f. See also specific type 6-Thioguanine, 290, 291f Thyroid hormone receptor-associated
Thiokinase (acyl-CoA synthetase)
Testosterone, 439f, 440f proteins (TRAPs), 472t, 473
binding of, 455, 455t in fatty acid activation, 180, 181f Thyroid hormone response element, 459t
metabolism of, 442, 444f in triacylglycerol synthesis, 199, 214f,
synthesis of, 442, 443f storage/secretion of, 453, 454t
215 Thyroid hormones, 437, 438
Testosterone-estrogen-binding globulin (sex Thiol-dependent transglutaminase. See
hormone-binding globulin), 455, in lipolysis, 215, 216f
455t, 583t Transglutaminase receptors for, 436, 471
Thiol ester plasma protein family, 590 synthesis of, 447–449, 448f
Tetracycline (tet) resistance genes, 402, Thiolase, 181, 182f, 184 transport of, 454, 454t
403f Thyroid-stimulating hormone (TSH), 437,
in mevalonate synthesis, 219, 220f
Tetrahedal transition state intermediate, in Thiophorase (succinyl-CoA- 438, 439f, 449
acid-base catalysis, 52, 53f Thyroperoxidase, 449
acetoacetate-CoA transferase), Thyrotropin-releasing hormone (TRH),
Tetrahydrofolate, 492, 493–494, 493f 133, 186, 186f
Tetraiodothyronine (thyroxine/T4), 438, Thioredoxin, 294 438, 439f
Thioredoxin reductase, 294, 297f Thyroxine (T4), 438, 447
447 Threonine, 15t
storage/secretion of, 453, 454t catabolism of, 253f, 255 storage/secretion of, 453, 454t
synthesis of, 447–449, 448f phosphorylated, 264 synthesis of, 447–449, 448f
transport of, 454, 454t requirements for, 480 transport of, 454, 454t
Tetramers Thrombin, 601, 602, 603f Thyroxine-binding globulin, 454, 454t
hemoglobin as, 42 antithrombin III affecting, 603–604 TIF2 coactivator, 472, 472t
histone, 314–315, 315 circulating levels of, 602–603 Tiglyl-CoA, catabolism of, 261f
Tetroses, 102, 102t conserved residues and, 55t TIM. See Translocase-of-the-inner
Tf. See Transferrin formation of fibrin and, 601–602, 603f
TFIIA, 350 in platelet activation, 606, 606f membrane
TFIIB, 350 Thrombolysis Timnodonic acid, 113t
TFIID, 346, 350, 351 laboratory tests in evaluation of, 608 Tin, 496t
in preinitiation complex formation, 352 t-PA and streptokinase in, 605, 605f, Tissue differentiation, retinoic acid in, 483
TFIIE, 350 606t Tissue factor complex, 601
TFIIF, 350 Thrombomodulin, in blood coagulation, Tissue factor (factor III), 599f, 600t, 601
TFIIH, 350 600t, 603, 607, 607t Tissue factor pathway inhibitor, 601
TFPI. See Tissue factor pathway inhibitor Thrombosis, 598–608. See also Coagulation Tissue plasminogen activator (alteplase/
TfR. See Transferrin receptor antithrombin III in prevention of,
Thalassemias, α and β, 47, 610t 603–604 t-PA), 604–605, 605, 605f,
recombinant DNA technology in circulating thrombin levels and, 602–603 606t, 607t
endothelial cell products in, 607, 607t Tissue-specific gene expression, 385
detection of, 408f, 409, 409t hyperhomocysteinemia and, folic acid Titin, 566t
Thanatophoric dysplasia, 551t supplements in prevention of, 494 TMP (thymidine monophosphate), 288f,
Theca cells, hormones produced by, 442 phases of, 598 288t
Theobromine, 289 in protein C or protein S deficiency, 603 Tocopherol, 482t, 486, 486f. See also
Theophylline, 289 t-PA and streptokinase in management Vitamin E
of, 605, 605f, 606t as antioxidant, 91, 119, 486, 487f
hormonal regulation of lipolysis and, 215 types of thrombi and, 598 deficiency of, 482t
Thermodynamics Thromboxane A2, 113f Tocotrienol, 486, 486f. See also Vitamin E
in platelet activation, 606f, 607 Tolbutamide, 188
biochemical (bioenergetics), 80–85. See Thromboxanes, 112, 113f, 190, 192 TOM. See Translocase-of-the-outer
also ATP clinical significance of, 196 membrane
cyclooxygenase pathway in formation of, Topogenic sequences, 506
glycolysis reversal and, 153–155 192, 193f Topoisomerases, DNA, 306, 328t, 332,
laws of, 80–81 Thymidine, 288t 332f
base pairing of in DNA, 303, 304, 305f Total iron-binding capacity, 586
hydrophobic interactions and, 7 Thymidine monophosphate (TMP), 288t Toxemia of pregnancy of ewes, ketosis and,
Thermogenesis, 217, 217f Thymidine-pseudouridine-cytidine (TΨC) 188
arm, of tRNA, 310, 312f, 360, Toxic hyperbilirubinemia, 283
diet-induced, 217, 478 361f Toxopheroxyl free radical, 486
Thermogenin, 217, 217f Thymidylate, 303 TpC. See Troponin C
Thiamin (vitamin B1), 482t, 488–489, 489f Thymine, 288t TpI. See Troponin I
TpT. See Troponin T
in citric acid cycle, 133 TR activator molecule 1 (TRAM-1
coenzymes derived from, 51 coactivator), 472, 472t
deficiency of, 482t, 489 TRAM (translocating chain-associated
membrane) protein, 504
pyruvate metabolism affected by, 140,
143, 489

Thiamin diphosphate, 140, 166, 488–489,
489f

Thiamin pyrophosphate, 50

690 / INDEX Transferrin, 478, 583t, 584–586, 585f, Transposition, 324–325
585t retroposons/retrotransposons and, 321,
TRAM-1 coactivator, 472, 472t 637
Trans fatty acids, 113–114, 192 Transferrin receptor, 586
Transaldolase, 166 Transfusion, ABO blood group and, 618 Transthyretin, 583t, 590
Transaminases. See Aminotransferases Transgenic animals, 385, 411–412, 414 Transverse asymmetry, 511
Transamination, 124, 124f Transversion mutations, 361, 361f
enhancers/regulatory elements identified TRAPs, 472t, 473
in amino acid carbon skeleton catabo- in, 386 Trauma, protein loss and, 480
lism, 249–250, 249f, 250f, 251f TRE. See Thyroid hormone response
Transglutaminase, in blood coagulation,
citric acid cycle in, 133–134, 134f 600, 600t, 602, 603f element
in urea biosynthesis, 243–244, 243f Trehalase, 475
Transcortin (corticosteroid-binding Transhydrogenase, proton-translocating, as Trehalose, 107t
source of intramitochondrial TRH. See Thyrotropin-releasing hormone
globulin), 454–455, 455t NADPH, 99 Triacylglycerols (triglycerides), 114, 115f,
Transcript profiling, 412
Transcription, 306, 350–352, 351t, 414 Transient insertion signal. See Signal 205
peptide digestion and absorption of, 475–477,
activators and coactivators in control of,
351, 351t Transition mutations, 361, 361f 476f
Transition state intermediate, tetrahedal, in excess of. See Hypertriacylglycerolemia
bacterial promoters in, 345–346, 345f interconvertability of, 231
control of fidelity and frequency of, acid-base catalysis, 52, 53f in lipoprotein core, 205, 207f
Transition states, 61 metabolism of, 123, 123f, 125–126,
344–350 Transition temperature/melting
eukaryotic promoters in, 346–349, 347f, 126f
temperature (Tm), 305, 422 in adipose tissue, 214–215, 214f
348f, 349f Transketolase, 163–166, 165f, 170 fatty liver and, 212, 213f
in gene expression regulation, 383–387, hepatic, 211–212, 213f
erythrocyte, in thiamin nutritional status high-density lipoproteins in,
391, 392t. See also Gene assessment, 489
expression 209–211, 211f
hormonal regulation of, 457, 458f, thiamin diphosphate in reactions hydrolysis in, 197
468–473, 470f, 471f, 472t involving, 166, 170, 488–489 reduction of serum levels of, drugs for,
initiation of, 342–343, 342f
NF-κB in regulation of, 468, 469f Translation, 358, 414 229
nuclear receptor coregulators in, Translocase-of-the-inner membrane, 499 synthesis of, 198f, 199
471–473, 472t Translocase-of-the-outer membrane, 499 transport of, 207, 208f, 209f, 210f
recombinant DNA technology and, 397, Translocating chain-associated membrane Tricarboxylate anions, transporter systems
398f
retinoic acid in regulation of, 483 (TRAM) protein, 504 for, 98–99
reverse, 414 Translocation, protein, 499 lipogenesis regulation and, 178
in retroviruses, 308, 332–333 Translocation complexes, 499 Tricarboxylic acid cycle. See Citric acid
in RNA synthesis, 306, 307f, 341–343, Translocon, 504
342f Transmembrane proteins, 419 cycle
Transcription complex, eukaryotic, 306, Triglycerides. See Triacylglycerols
350–352, 351t ion channels as, 423–424, 425f, 426t Triiodothyronine (T3), 438, 447
Transcription control elements, 351, 351t in red cells, 615–616, 615f, 616f, 616t
Transcription domains, definition of, Transmembrane signaling, 415, 431 storage/secretion of, 453, 454t
387 in platelet activation, 606, 606f synthesis of, 447–449, 448f
Transcription factors, 351, 351t Transmissible spongiform encephalopathies transport of, 454, 454t
nuclear receptor superfamily, 469–471, Trimethoprim, 494
471f, 472t (prion diseases), 37 Trinucleotide repeat expansions, 322
Transcription start sites, alternative, Transport proteins, 454–456, 454t, 455t, Triokinase, 167, 169f
393–394 Triose phosphates, acylation of, 123
Transcription unit, 342, 345f 583t Trioses, 102, 102t
Transcriptional intermediary factor 2 (TIF2 Transport systems/transporters. See also Triphosphates, nucleoside, 287, 287f
coactivator), 472, 472t Triple helix structure, of collagen, 38, 38f,
Transcriptome information, 412, 414 specific type
Transfection, identification of active, 423, 423t, 424f, 426–427, 535–539, 536f
enhancers/regulatory elements Triplet code, genetic code as, 358, 359t
and, 386 427–428, 428f tRNA. See Transfer RNA
Transfer RNA (tRNA), 308, 310, 312f, ADP/ATP, 95, 98f Tropocollagen, 38, 38f
341, 342t, 360–361, 361f. See ATP-binding cassette, 210, 211f Tropoelastin, 539
also RNA in cotranslational insertion, 506, 506f Tropomyosin, 557, 559f, 562
aminoacyl, in protein synthesis, 368 disorders associated with mutations in
anticodon region of, 359 in red cell membranes, 616t
processing and modification of, 355, 356 genes encoding, 512t, 513 as striated muscle inhibitor, 563
suppressor, 363 exchange, 98–100, 98f, 99f Troponin/troponin complex, 557, 559f,
Transferases, 50 facilitated diffusion, 423, 423t, 424f,
562
426–427, 427, 427f as striated muscle inhibitor, 563
glucose. See Glucose transporters Troponin C, 562
in inner mitochondrial membrane,

98–100, 98f, 99f
membrane, 426–431, 426f
for nucleotide sugars, 517
Transport vesicles, 498, 508–511, 509t,

510f

Troponin I, 562 Ubiquinone (Q/coenzyme Q), 92, 95f, 118 INDEX / 691
Troponin T, 562 in cholesterol synthesis, 220, 221f
Trypsin, 477 Uridine diphosphate N-acetylgalactosamine
UDP-glucose. See Uridine diphosphate (UDP-GalNAc), 516t
conserved residues and, 55t glucose
in digestion, 477 Uridine diphosphate N-acetylglucosamine
for polypeptide cleavage, 25, 26t UDPGal. See Uridine diphosphate galactose (UDP-GlcNAc), 516t
Trypsinogen, 477 UDPGlc. See Uridine diphosphate glucose
Tryptophan, 16t, 266–267, 490 UFA (unesterified fatty acids). See Free fatty Uridine diphosphate galactose (UDPGal),
catabolism of, 257f, 258, 258f 167, 516–517, 516t
deficiency of, 490 acids
niacin synthesized from, 490 Ulcers, 474 Uridine diphosphate galactose (UDPGal)
permeability coefficient of, 419f Ultraviolet light 4-epimerase, 167, 170f
requirements for, 480
Tryptophan oxygenase/L-tryptophan nucleotide absorption of, 290 inherited defects in, 172
nucleotide excision-repair of DNA Uridine diphosphate glucose
oxygenase (tryptophan
pyrrolase), 89, 257f, 258 damage caused by, 337 (UDP/UDPGlc), 145, 147f,
TSEs. See Transmissible spongiform vitamin D synthesis and, 484, 485f 516, 516t
encephalopathies UMP (uridine monophosphate), 288f, 288t in glycogen biosynthesis, 145, 146f
TSH. See Thyroid-stimulating hormone Uncouplers/uncoupling proteins Uridine diphosphate glucose dehydroge-
α-Tubulin, 577 in respiratory chain, 95, 96f nase, 166, 168f
β-Tubulin, 577 Uridine diphosphate glucose
γ-Tubulin, 577 chemiosmotic theory of action of, 97 pyrophosphorylase, 166, 168f
Tumor cells, migration of, hyaluronic acid undernutrition and, 479 in glycogen biosynthesis, 145, 146f
and, 548 Undernutrition, 474, 478–479 Uridine diphosphate-glucuronate/glu-
Tumor suppressor genes, p53, 339 Unequal crossover, 324, 324f curonic acid, 166–167, 168f, 290
Tunicamycin, 527, 527t Unesterified fatty acids. See Free fatty acids Uridine diphosphate xylose (UDP-Xyl),
β-Turn, 32, 34f Uniport systems, 426, 426f 516t
Twin lamb disease. See Pregnancy toxemia Unique-sequence (nonrepetitive) DNA, Uridine monophosphate (UMP), 288f,
of ewes 288t
Twitch fibers, slow (red) and fast (white), 320, 320–321 Uridine triphosphate (UTP), in glycogen
574–576, 575t Universal donor/universal recipient, 618 biosynthesis, 145, 146f
Two-dimensional electrophoresis, protein Unsaturated fatty acids, 111, 112, 113t. See Uridyl transferase deficiency, 172
expression and, 28 Urobilinogens
TXs. See Thromboxanes also Fatty acids conjugated bilirubin reduced to, 281,
Tyk-2, in Jak-STAT pathway, 467 cis double bonds in, 112–114, 114f 282f
Type A response, in gene expression, 374, dietary, cholesterol levels affected by, in jaundice, 284, 284t
375f normal values for, 284t
Type B response, in gene expression, 227 Urocanic aciduria, 250
374–375, 375f eicosanoids formed from, 190, 192, Urokinase, 605, 605f
Type C response, in gene expression, 375, Uronic acid pathway, 163, 166–167, 168f
375f 193f, 194f disruption of, 170
Tyrosine, 15t, 16t, 267, 267f essential, 190, 190f, 193 Uronic acids, 109
catabolism of, 254f, 255 in heparin, 545, 545f
epinephrine and norepinephrine formed abnormal metabolism of, 195–196 Uroporphyrinogen I, 271, 274f, 275f
from, 267, 267f deficiency of, 191–192, 194–195 Uroporphyrinogen I synthase, in porphyria,
in hemoglobin M, 46 prostaglandin production and, 190 277t
in hormone synthesis, 438, 439–449, in membranes, 417, 418f Uroporphyrinogen III, 271, 274f, 275f
439t metabolism of, 190–192 Uroporphyrinogen decarboxylase, 271,
phosphorylated, 264 oxidation of, 183 275f
requirements for, 480 structures of, 190f in porphyria, 277t
synthesis of, 239, 240f synthesis of, 191, 191f Uroporphyrins, 270, 271f, 272f
Tyrosine aminotransferase, defect in, in Unwinding, DNA, 326, 326–327 spectrophotometry in detection of,
tyrosinemia, 255 RNA synthesis and, 344 273–274
Tyrosine hydroxylase, catecholamine Uracil, 288t UTP, in phosphorylation, 85
biosynthesis and, 446, 447f deoxyribonucleosides of, in pyrimidine
Tyrosine kinase V8 protease, for polypeptide cleavage, for
in insulin signal transmission, 465–467, synthesis, 296–297, 298f polypeptide cleavage, 25, 26t
466f Urate, as antioxidant, 119
in Jak/STAT pathway, 467, 467f Urea vi. See Initial velocity
Tyrosinemia, 255 Vmax. See Maximal velocity
Tyrosinosis, 255 amino acid metabolism and, 124, 124f V region/segment. See Variable regions/
nitrogen catabolism producing,
segments
242–243, 245–247, 246f v-SNARE proteins, 509, 511
permeability coefficient of, 419f Valeric acid, 112t
synthesis of, 243–244, 243f, 244f Valine, 15t

metabolic disorders associated with, catabolism of, 259, 260f, 262f
247–248

gene therapy for, 248
Uric acid, 289

purine catabolism in formation of, 299,
299f

Uridine, 287f, 288t

692 / INDEX Vitamin B complex. See also specific vitamin in coagulation, 486–488, 488f
in citric acid cycle, 133 coumarin anticoagulants affecting,
Valine (cont.) coenzymes derived from, 50–51, 51f 604
interconversion of, 240
requirements for, 480 Vitamin B1 (thiamin), 482t, 488–489, 489f deficiency of, 482t
in citric acid cycle, 133 Vitamin K hydroquinone, 487, 488f
Valinomycin, 99 coenzymes derived from, 51 Vitamins, 2, 481–496, 482t. See also spe-
Van der Waals forces, 7 deficiency of, 482t, 489
Vanadium, 496t pyruvate metabolism affected by, 140, cific vitamin
Variable numbers of tandemly repeated 143, 489 in citric acid cycle, 133
digestion and absorption of, 477–478
units (VNTRs), in forensic Vitamin B2 (riboflavin), 86, 482t, 489–490 lipid- (fat) soluble, 482–488
medicine, 411 in citric acid cycle, 133
Variable regions/segments, 591–592, 594f coenzymes derived from, 50–51, 489, absorption of, 475
gene for, 593 490 water-soluble, 488–496
DNA rearrangement and, 325–326, deficiency of, 482t, 490 VLA-1/VLA-5/VLA-6, 622t
393, 593–594 dehydrogenases dependent on, 87 VLDL. See Very low density lipoproteins
immunoglobulin heavy chain, 591, 592f, VNTRs. See Variable numbers of tandemly
594f Vitamin B6 (pyridoxine/pyridoxal/
immunoglobulin light chain, 325–326, pyridoxamine), 482t, 491, 491f repeated units
393, 591, 592f, 594f Voltage-gated channels, 424, 568t
Vascular system, nitric oxide affecting, deficiency of, 482t, 491 von Gierke’s disease, 152t, 300
571–573, 573f, 574t xanthurenate excretion in, 258, 258f Von Willebrand factor, in platelet
Vasodilators, 556
nitric oxide as, 571–573, 573f, 574t excess/toxicity of, 491 activation, 605
VDRE. See Vitamin D response element Vitamin B12 (cobalamin), 482t, 491–492,
Vector, 414 Warfarin, 486, 604
cloning, 400–402, 401f, 402t, 403f, 414 492f phenobarbital interaction and,
expression, 402 absorption of, 491–492 cytochrome P450 induction
Vegetarian diet, vitamin B12 deficiency and, affecting, 628
491 intrinsic factor in, 477, 491–492 vitamin K affected by, 487
Velocity deficiency of, 482t, 492
initial, 64 Water, 2, 5–9
inhibitors affecting, 68, 68f, 69f functional folate deficiency and, 492, as biologic solvent, 5, 6f
maximal (Vmax) 494 biomolecular structure and, 6–7, 6t
allosteric effects on, 75–76 dissociation of, 8–9
inhibitors affecting, 68, 68f, 69f in methylmalonic aciduria, 155 in hydrogen bonds, 5, 6f
Michaelis-Menten equation in Vitamin B12-dependent enzymes, 292f, 492 as nucleophile, 7–9
determination of, 65–66, 66f Vitamin C (ascorbic acid), 163, 482t, permeability coefficient of, 419f
substrate concentration and, 64, 64f structure of, 5, 6f
Very low density lipoprotein receptor, 208 495–496, 496f
Very low density lipoproteins, 125, 205, as antioxidant, 119 Water solubility, of xenobiotics, metabolism
206t, 207 in collagen synthesis, 38, 496, 535 and, 626
hepatic secretion of, dietary and hormonal deficiency of, 482t, 496
status and, 211–212, 213f Watson-Crick base pairing, 7, 303
metabolism of, 125, 126f, 207–209, 210f collagen affected in, 38–39, 496, Waxes, 111
in triacylglycerol transport, 207, 208f, 538–539 Weak acids, 9
210f
Vesicles iron absorption and, 478, 496 buffering capacity of, 11–12, 12f
coating, 509, 510f supplemental, 496 dissociation constants for, 10–11, 12
brefeldin A affecting, 510–511 Vitamin D, 482t, 484–486 Henderson-Hasselbalch equation
secretory, 498, 500f in calcium absorption, 477, 484,
targeting, 509, 510f describing behavior of, 11, 12f
transport, 498, 508–511, 509t, 510f 484–485 physiologic significance of, 10–11
Vimentins, 577t, 578 deficiency of, 482t, 484, 485 pK/pKa values of, 10–13, 12t,
Vinculin, 540, 541f ergosterol as precursor for, 118, 119f Weak bases, 9
Viral oncogenes. See Oncogenes excess/toxicity of, 485–486 Wernicke-Korsakoff syndrome, 482t
Viruses, host cell protein synthesis affected metabolism of, 484–485, 485f Wernicke’s encephalopathy, 489
by, 370–371, 371f receptor for, 471 Western blot transfer procedure, 403, 404f,
Vision, vitamin A in, 482t, 483, 484f Vitamin D2 (ergocalciferol), 484
Vitamin A, 482–484, 482t, 483f, 484f Vitamin D3 (cholecalciferol) 414
deficiency of, 482t, 483–484 synthesis of in skin, 445, 446f, 484, 485f White blood cells, 620–624. See also specific
excess/toxicity of, 484 in vitamin D metabolism, 484, 485f
functions of, 482t, 483 Vitamin D-binding protein, 445 type
in vision, 482t, 483 Vitamin D receptor-interacting proteins growth factors regulating production of,

(DRIPs), 472t, 473 610
Vitamin D response element, 459t recombinant DNA technology in study
Vitamin E, 482t, 486, 486f
of, 624
as antioxidant, 91, 119, 486, 487f White thrombus, 598
deficiency of, 482t, 486 White (fast) twitch fibers, 574–576, 575t
Vitamin H. See Biotin Whole genome shotgun approach, 634
Vitamin K, 482t, 486–488, 488f, 604 Williams syndrome, 539
calcium-binding proteins and, 487–488,

488f

Wilson disease, 432t, 587–589 responses to, 630–631, 630t, INDEX / 693
ceruloplasmin levels in, 587 631t
gene mutations in, 432t, 588–589 Z line, 556, 557f, 558f
toxic, 631, 631f Zellweger’s (cerebrohepatorenal) syndrome,
Wobble, 361 Xeroderma pigmentosum, 337
Xerophthalmia, vitamin A deficiency in, 188, 503, 503t
X-linked disorders, RFLPs in diagnosis of, Zinc, 496t
411 482t, 483 Zinc finger motif, 387, 388t, 390, 390f
XP. See Xeroderma pigmentosum
X-ray diffraction and crystallography, Xylose, in glycoproteins, 516t in DNA-binding domain, 470
protein structure D-Xylose, 104f, 105t Zona fasciculata, steroid synthesis in, 440
demonstrated by, 35 D-Xylulose, 106f Zona glomerulosa, mineralocorticoid
L-Xylulose, 105t
Xanthine, 289 synthesis in, 438
Xanthine oxidase, 87 accumulation of in essential pentosuria, Zona pellucida, glycoproteins in, 528
170 Zona reticularis, steroid synthesis in,
deficiency of, hypouricemia and, 300
Xanthurenate, excretion of in vitamin B6 YAC vector. See Yeast artificial chromosome 440
(YAC) vector ZP. See Zona pellucida
deficiency, 258, 258f ZP1–3 proteins, 528
Xenobiotics, metabolism of, 626–632 Yeast artificial chromosome (YAC) vector, Zwitterions, 16
401–402, 402t Zymogens, 76, 477
conjugation in, 626, 628–630
cytochrome P450 system/hydroxylation for cloning in gene isolation, 635t in blood coagulation, 600, 600t, 601
Yeast cells, mitochondrial protein import rapid response to physiologic demand
in, 626–628, 629t
factors affecting, 630 studied in, 499 and, 76
pharmacogenetics in drug research and, ZZ genotype, α1-antiproteinase deficiency

631–632 and
in emphysema, 589
in liver disease, 590