Comprehensive Biochemistry for Dentistry Textbook for Dental Students

4.8  Other Important Plasma Proteins 73

4.7.3 H emopexin

• Characteristics
–– It is a beta globulin. It is made up of a single polypeptide chain of 439 amino
acids.
–– It is synthesized in the liver.
–– Hemopexin has the strongest affinity for binding with “heme.” This affinity is
the highest among known proteins. Hemopexin binds to heme in 1:1 ratio.
–– Its serum concentration is between 50 and 100 mg/100 ml in adults. In infancy,
its serum concentration is low, and it comes up to adult serum level within first
year of life.
–– Hemopexin has the cytoprotective and antioxidant properties similar to
haptoglobin.

• Clinical significance
–– Serum hemopexin level is decreased in hemolytic anemia. So it has a diagnos-
tic value for assessing hemoglobin level and RBC count.

4.8 O ther Important Plasma Proteins

4.8.1 Bence-Jones Protein

• Characteristics
–– It is a paraprotein (an antibody that arises from rapid proliferation of
monoclonal plasma cells during malignancy).
–– It is an abnormal immunoglobulin.
–– Its molecular weight is 45,000.
–– It is made up of immunoglobulin light chain. So it is a subunit of a normal
immunoglobulin.
–– Light chain can be either kappa (κ) chain or lambda (λ) chain.
–– Light chain is made up of around 217 amino acids.

• Clinical Significance
–– Bence-Jones protein appears in blood and urine in persons suffering from
multiple myeloma. It is a tumor of plasma cells. Normally, plasma cells pro-
duce thousands of antibodies which are grouped into five categories, such as
IgA, IgG, IgM, IgD, and IgE. Tumor plasma cell produces a particular type of
antibody in large excess.
–– Serum paraprotein concentration more than 3 mg/100 ml is a diagnostic of
multiple myeloma.
–– This protein is identified by heating a sample of urine to 60 °C temperature.
The protein gets precipitated. Further heating of urine dissolves the precipi-
tate. If the urine sample is cooled under tap water, the precipitate reappears.

74 4  Plasma Proteins

4.8.2 F ibrinogen

• Characteristics
–– It is a soluble plasma protein. It is called clotting factor I.
–– Fibrinogen is the precursor to fibrin, which is necessary for blood clotting.
–– It is synthesized in the liver.
–– Its normal serum concentration is 200–400 mg/100 ml in adults.
–– It is a hexameric protein. It is made up of two Aα chains, two Bβ chains, and
two γ polypeptide chains. These chains are interlinked by disulfide bridges.
–– Its molecular weight is between 350,000 and 450,000.
–– Fibrinogen molecule has a highly elongated structure with an axial ratio of
20:1.

• Clinical Significance
–– Fibrinogen is necessary for blood clotting.
–– Its serum concentration is decreased in liver diseases.
–– Its low serum concentration is correlated to higher bleeding tendency.
–– Fibrinogen is an acute-phase reactant protein. It is a biomarker of coronary
heart disease.

4.9 B iological Functions of Plasma Proteins

• Acid-base Regulation
–– Plasma proteins are amphoteric in nature. So they can buffer an acid or base
in blood. It helps to maintain acid-base balance of blood and body fluid.

• Colloidal Osmotic Pressure (Oncotic Pressure)
–– Plasma proteins offer colloidal osmotic pressure. It is normally about 25 mm
of Hg. Albumin exerts maximum COP due its larger concentration in plasma.
Colloidal osmotic pressure is necessary for normal distribution of body water
in blood vessels and interstitial spaces.

• Role in Blood Clotting
–– Plasma contains fibrinogen, prothrombin, and other blood clotting factors in
inactive form. At the time of injury, these components are activated in a cas-
cade fashion and helps in blood clotting.

• Role in Immunity
–– Plasma contains immunoglobulins. These are synthesized by B lymphocytes.
They protect the body against pathogens.

• Role in Transport of Substances
–– Albumin and globulins transport large substance from blood to tissues. Drugs,
hormones, and enzymes are transported by plasma proteins.

• Nutritive Role
–– Plasma proteins are simple proteins. They are source of amino acids. So they
have play a nutritive role in the body.

Suggested Readings 75

• Blood Viscosity maintenance
–– Plasma proteins make the blood viscous. It is due to presence of globulins and
fibrinogen in plasma. Blood viscosity is necessary for maintenance of normal
blood pressure.

• Storage of Enzymes
–– Plasma is a store house of several enzymes like, lipase, amylase, and trans-
aminases in minute amounts. The variation in the amount of plasma enzymes
is helpful in the diagnosis and prognosis of diseases.

• Act as Reserve Proteins
–– Under fasting condition, plasma proteins are broken down to amino acids.
These are carried to tissues by blood circulation. They are utilized by tissues
for synthesis of tissue proteins.

Suggested Readings

Alberti KGMN (ed) (1978) Recent advances in clinical biochemistry. Churchill Livingstone,
London

Baron DN (1982) A short textbook of chemical pathology, 4th edn. Wiley, New York
Conn EE, Stump PK (1969) Outline of biochemistry, 2nd edn. Wiley, New Delhi

Hemoglobin 5

5.1 Definition

Hemoglobin

• Hemoglobin refers to a red colored conjugated protein consisting of heme as
prosthetic group and globin as an apoprotein.

Nature of Hemoglobin

• Hemoglobin is a metalloprotein owing to presence of ferrous ions as prosthetic
moiety.

Chromoprotein

• Hemoglobin is a chromoprotein owing to presence of a pigmented prosthetic
moiety.

5.2 Characteristics of Hemoglobin

• Hemoglobin constitutes about 95% of dry weight and 35% of wet weight of
erythrocytes.

• Normal Concentration of Hemoglobin
–– At birth: 23 g%
–– After infancy: 12.5 g%
–– Adult males: 14–18 g%

© Springer Nature Singapore Pte Ltd. 2019 77
A. Gupta, Comprehensive Biochemistry for Dentistry,
https://doi.org/10.1007/978-981-13-1035-5_5

78 5 Hemoglobin

–– Adult females: 12–16 g%
–– Clinical value: 14.7 g% regardless of gender variation
• Hemoglobin is an essentiality for life of aerobic organisms including
humans.

5.3 Structure of Hemoglobin

• Hemoglobin is composed of two components as:
–– Apoprotein: It is called globin.
–– Prosthetic group: It is called heme.

• Globin
It is a globular protein. It is composed of four polypeptide chains. Depending
on number and sequence of amino acid residues, chains are designated as:
–– α chains
Globin contains two α chains. Each one is composed of 141 amino acid
residues.
–– β chains
–– Globin contains two β chains. Each one is composed of 146 amino acid
residues.

• Hydrophobic amino acids are located interiorly, and hydrophilic amino acids are
placed externally in hemoglobin polypeptide chains. This feature makes hemo-
globin water soluble. Cluster of hydrophobic amino acid residues constitutes
hydrophobic or heme pocket in each polypeptide chain.

• Each heme pocket contains one heme moiety. Therefore, one hemoglobin mole-
cule contains four heme moieties.

Hemoglobin is heterotetramer composed of two α chains and two β chains.

5.3.1 Heme

Heme is iron-protoporphyrin IX complex. Its structure is described as
follows:

Structure of Protoporphyrin IX
It is a common type of porphyrin. It is a planar molecule. It has tetrapyrrole struc-
ture which is composed of four pyrrole rings fused together.

• Pyrrole ring: It is a five-membered ring made of four carbon atoms and one
nitrogen atom as in Fig. 5.1. Pyrrole rings are numbered from I to IV. They are
interlinked with methyne bridges (〓CH–).These bridges are labeled as α, β, γ,
and δ, respectively. Inner carbon atoms of pyrrole rings are linked to methyne
bridges.

5.3  Structure of Hemoglobin 79

Fig. 5.1  Pyrrole ring HC CH

HC CH

NH

Fig. 5.2  Structure of Methyl group Vinyl
hemoglobin group

H3C – C1 I C2 – CH= CH2 H3C – C3 C4 – CH= CH2
C IV C CH C II

Fe++ C
IV
δ CH
β CH

N N
C
C γ
IV CH III
C5 – CH3
H3C – C8 C7 H26
Propionic acid
CH2 HOOC – CH2 – C
CH2
COOH N - atom of imidazole
ring of histidine

]Globin

• Outer carbon atoms of pyrrole rings are free and numbered from 1 to 8. Hydrogen

atoms from positions 1 to 8 are substituted by different groups.
• Hydrogen atoms at positions 1, 3, 5, and 8 are substituted by methyl groups (–

CH3), while at positions 2 and 4 are substituted by vinyl groups (–CH〓CH2),
and positions 6 and 7 are replaced with propionic acid groups (–CH2.CH2.
COOH) as in Fig. 5.2.

Valencies of Iron

• Iron in heme exists in ferrous state. Ferrous iron has valence 6 and has 6
coordinate positions.

• Iron is positioned at the center of tetrapyrrole. Ferrous iron is attached to
four nitrogen atoms (N) of pyrrole rings by four coordinative bonds.

80 5 Hemoglobin

• Ferrous iron is also linked to nitrogen (N) atom of imidazole ring of histidine
amino acid residue in polypeptide chain through its fifth coordinative position.

• In oxygenated state, ferrous iron is linked reversibly to one molecule of oxygen
through sixth coordinative bond.

• In deoxygenated state, sixth coordinative position of iron is occupied by H2O
molecule.

A hemoglobin molecule:

• Contains four polypeptide chains
• Contains four heme moieties
• Contains four ferrous atoms
• Carries four oxygen molecules

Binding of hemoglobin with oxygen molecule is called as oxygenation. This
process is not called oxidation because iron remains in ferrous state in
oxyhemoglobin.

5.4 T wo-State Model of Hemoglobin

It is called as Monod-Wyman-Changeux model of hemoglobin.

Basis of Model

• An allosteric protein (a protein that can have many sites for binding with multi-
ple ligands) is made up of multiple subunits.

• Each subunit has ability to exist in two conformational states as tense state (T)
and relaxed state (R).

• These two conformers (T and R) are in equilibrium with each other.

Hemoglobin molecule is a tetramer with four subunits which are arranged
in two identical dimers.

Each dimer has one α-subunit and one β-subunit and are designated as
(α1β1) and (α2β2).

They are held together by non-covalent forces.
Depending on relative position of dimmers and affinity toward ligand, hemoglo-
bin molecule exhibits two thermodynamic forms as follows:

“T” Form of Hemoglobin

• T represents tense form of hemoglobin. Non-covalent forces restrict conforma-
tional change both within dimer and between two dimmers. Hemoglobin has less
affinity to oxygen molecule in T form. This form is deoxy form of hemoglobin.

5.4  Two-State Model of Hemoglobin 81

The oxygen binding coordinate site of ferrous iron is vacant. It is occupied by a

water molecule. Low pO2, high pCO2, and low pH always favor T form of hemo-
globin as in Fig. 5.3.
• R represents relaxed form of hemoglobin. In a heme residue, binding of oxygen

to Fe++ iron brings about rearrangement of its electrons. Ferrous iron undergoes

a change in its position and comes to lie in plane of protoporphyrin ring as in

Fig. 5.4.

Fig. 5.3  T form of N N
hemoglobin

Fe++ Iron is

N N Domed

N

N
H
Deoxy haemoglobin

[ T- Form]

Fig. 5.4  R form of H
hemoglobin Hydogen bonding

N O ON

Iron is Fe++
planar
N
N

N

N
H
Oxy haemoglobin

[R- Form]

82 5 Hemoglobin

• Ferrous iron is attached to proximal histidine in polypeptide chain; therefore,
shift in position of iron induces a change in histidine position. Finally, one poly-
peptide chain undergoes conformational shift.

• Conclusively, relative interactions between one polypeptide chain and contigu-
ous polypeptide chains undergo complete shift. One dimer undergoes rotation of
15 degrees relative to position of adjacent dimer in hemoglobin molecule.

• The conformational change enhances affinity of heme residues to oxygen.
Therefore, every additional oxygen molecule binds with higher affinity in
comparison with earlier oxygen molecule, and this property is called coop-
erative binding.

• R form oxy form of hemoglobin.
• High pO2, low pCO2, and high pH always favor R form of hemoglobin.
• T form is deoxy form of hemoglobin.
• High pCO2, low pO2, and low pH always favor T form of hemoglobin.
• Rotation of one dimer relative to other dimer is responsible for interconver-

sion of T form into R form and vice versa.

5.5 Functions of Hemoglobin

1. It helps in transportation of oxygen from pulmonary alveoli to body tissues.
2. It transports carbon dioxide from body tissues to pulmonary alveoli.
3 . It also acts as protein buffer which is an important buffer of plasma.

5.6 V ariants of Hemoglobin

Various types of hemoglobin are found in population. Hemoglobin variants are due
to different globin genes which control synthesis of globin chains as follows:

• Chromosome 16
• Two α-globin genes are located on each chromosome 16
• Chromosome 11
• This chromosome contains three types of genes as:
• Single β-globin gene on each chromosome 11
• Two γ-globin genes and one δ-globin gene

These variants are expressed due to gene expression. These variants differ in
their structure of globin fraction of hemoglobin molecule. Throughout all variants,
heme moiety remains unaltered.

Normal hemoglobin variants neither exhibit any biochemical changes nor
clinical manifestation in the individuals.

5.6  Variants of Hemoglobin 83

5.6.1 Adult Hemoglobin (HbA)

It is normal hemoglobin in adult population. It exists into two forms as:

• Hemoglobin A
• Hemoglobin A2

Hemoglobin A (HbA)
It is composed of 2α chains and 2β chains. It is designated as (α2 β2). This hemo-
globin is found in 90–95% of adult population.

Hemoglobin A2 (HbA2)
It is composed of 2α chains and 2δ chains. It is designated as (α2 δ2). Beta chains
are substituted by delta chains. Each delta chain contains 146 amino acids. Delta
chain has ten amino acid residues different from beta chain. This Hb is found in
around 2.5% of adult population.

5.6.2 F etal Hemoglobin (HbF)

• It is composed of 2α chains and 2γ chains. It is designated as (α2 γ2). Beta
chains are substituted by gamma chains. Each gamma chain has 146 amino acid
residues. It has 37 amino acids different from beta chains.

• Fetal Hb is the predominant hemoglobin during 20th-week period of intra-
uterine life.

• HbF has much higher affinity for oxygen. At pO2 of 20 mm of Hg, oxygen
saturation of HbA is 35% and HbF is 70%.
It can transport greater volume of oxygen at low partial pressure of oxygen. This
characteristic is helpful in oxygen transport from maternal circulation to fetus.

• At birth, fetal hemoglobin represents 80% of the total Hb of the body of infant.
It is replaced by adult Hb after 6–12 months.

5.6.3 G lycosylated Hemoglobin (HbA1C)

It is a form of adult hemoglobin. A small fraction of hemoglobin undergoes glyco-
sylation with glucose moiety. It is designated as HbA1c. It represents nearly 2% of
total adult hemoglobin. However, individuals suffering from diabetes mellitus pos-
sess higher proportion of glycosylated Hb (5–10%).

Its amino acid number and sequence are similar to adult hemoglobin. It differs
from HbA in having a sugar residue linked to valine amino acid residue by
glycosylation.

84 5 Hemoglobin

5.7 Hemoglobinopathies

Hemoglobinopathies refer to group of genetic disorders producing abnormal-
ity in structure of one of the globin chains and is characterized by altered bio-
chemical reactions and clinical manifestation in the body of individuals.

Variants of Abnormal Hemoglobin
Globin synthesis is regulated by genes. A pair of α-globin genes and a pair of
β-globin genes are located on chromosomes 16 and 11. They control translation of
two α and β polypeptide chains. Mutation in globin genes is responsible for altered
structure of globin chains.

Gene mutation manifests into mutant hemoglobin which in turn expresses into
clinical signs and symptoms.

Therefore, abnormal hemoglobin is mutant hemoglobin. There are more than
1000 variants of abnormal hemoglobin which have been detected. They can be cat-
egorized into two groups depending on type of gene mutation as:

Mutation in Structural Gene

• This mutation is responsible for substitution of an amino acid residue in adult
hemoglobin by another amino acid residue. Sequence of amino acid residues is
affected. Synthesis of polypeptide chains remains unaffected.
Example: HbS, HbD

Mutation in Regulatory Gene

• This mutation affects synthesis of polypeptide chains. This condition manifests
either affected synthesis of alpha chain or beta chain, and disorder is termed as
thalassemia.

5.7.1 Sickle-Cell Hemoglobin (HbS)

It is the hemoglobin that is contained in sickle-shaped (crescent-shaped) erythro-
cytes. It is a highly frequent variant of abnormal hemoglobin in population.

Occurrence
This disorder was mentioned by James B Herrick, an American physician in 1930.

Sickle-cell anemia is more common in African countries. Black population is
more prone to occurrence of disease. According to an estimate, more than 80% of
sickle-cell anemia sufferers are confined to Southern Africa.

Characteristics of Sickle-Cell Hemoglobin

• It is an abnormal hemoglobin with deviated structure. It has two alpha
chains which are normal. They have amino acid sequence similar to that of
adult hemoglobin.

5.7 Hemoglobinopathies 85

• Two beta chains have altered sequence of amino acid residues.
• Amino acid glutamic acid at sixth position in each beta chain is substituted by

valine amino acid.

Pathogenesis

• Defect is caused by a mutant β-globin gene located on chromosome 11.
• Glutamic acid is a polar amino acid, and it is replaced with non-polar, valine

amino acid. It results into formation of a sticky patch on the outer surface of beta
chains.
• Sticky patch is found in oxygenated state of hemoglobin-S (R form) as well as
deoxygenated state of hemoglobin-S (T form). Sticky patch is absent in oxygen-
ated state of HbA.
• Deoxygenate state of Hb-S also contains a site complementary to sticky patch
and is called as complementary site.
• Complementary site on oxygenated state of Hb-S is masked.

During deoxygenation of Hb-S, sticky patch of one molecule can bind with comple-
mentary site of another molecule. It results into polymerization of deoxygenated
Hb-S molecules. They are manifested as long fibrous polymers that extend across
the interior of erythrocytes. These fibers bring about distortion in shape of
erythrocytes.

During oxygenation of Hb-S, sticky patch of one molecule cannot bind with
complementary site of another molecule as complementary site is masked.

Distortion in shape of erythrocytes can be minimized by either of two fac-
tors as:

• Deoxygenation of Hb-S should be minimized.
• Oxygenation of Hb-S should be prolonged.

Effects of Sickle-Cell Anemia
Hemolytic Anemia

• Erythrocytes become fragile.
• They have increased tendency to rupture.
• It results into repeated and excessive hemolysis.
• Its manifestation is hemolytic anemia.

Damage of Body Tissues

• Sickle-shaped erythrocytes have tendency to become lodged into capillaries.
• It results into low perfusion of body organs.
• Low blood perfusion into organs causes hypoxia and necrosis of tissues.

86 5 Hemoglobin

Predisposition to Infection

• Hemolytic anemia is accompanied by poor nutrition and weak immunity.
• Affected individuals develop high disposition to infections.

Short Life Span

• Life span of homozygous suffers is limited.
• They die before age of 20 years.

5.7.2 S ickle-Cell Trait

It is a disorder characterized by heterozygous condition of β-globin gene.
Sickle-cell anemia is caused by mutant β-globin gene.
Mutant genes exhibit two conditions as:

Homozygous Genes
In this condition, both genes are mutant. One gene is inherited from the father and
other one from the mother. Both beta chains are structurally abnormal. This condi-
tion is homozygous.

Individuals with heterozygous genes suffer from sickle-cell anemia.

Heterozygous Genes
In this condition, one inherited gene is mutant, while the other gene is normal. One
beta chain is structurally abnormal, while the other one is normal. This condition is
heterozygous.

Individuals with heterozygous genes are carriers of sickle-cell anemia. They do
not suffer from clinical manifestations of disorder. They have a normal life span.

Clinical Significance of Sickle-Cell Trait
Plasmodium falciparum is a malarial parasite. Its incidence is highest in tropical
areas of the world. It is associated with high rate of mortality and morbidity.
Coincidentally, sickle-cell trait is higher in tropical areas of the world.

It has been found that sickle-cell trait offers resistance against malaria. The
fact is based on following assumptions as:

• High tendency for hemolysis in sickle-cell anemia.
• Rupture of erythrocytes disrupts the life cycle of parasite.
• Infestation of malarial parasites inside erythrocytes decreases pH of erythro-

cytes. This condition further aggravates distortion in shape of erythrocytes
(>sickling).
• Increasing rate of RBC sickling helps to interrupt plasmodium life cycle.

Sickle-cell trait has become an adaptation among humans to malaria for
survival.

5.7 Hemoglobinopathies 87

5.7.3 H emoglobin C (HbC)

The alpha chains are two in number. Each chain has the same sequence of amino
acid residues as in adult Hb. The beta chains undergo change in sequence of amino
acid residues. In each beta chain, glutamic acid is replaced by lysine amino acid at
6th position.

The condition is called as Cooley’s hemoglobinemia. It is characterized by
hemolytic anemia in affected individuals.

5.7.4 H emoglobin D (HbD)

This hemoglobin has normal alpha chains. In each beta chain, glutamic acid is
replaced by glutamine at 12th position. This hemoglobin has several varieties which
have been identified from different regions. Example: HbD (Punjab)

5.7.5 H emoglobin E (HbE)

This variant of hemoglobin is common in population. It has been estimated that
nearly 15% of Southeast Asian population is suffering from HbE disorder.

The two alpha chains have the same sequence of amino acid residues as found in
adult hemoglobin. In each beta chain, glutamic acid is substituted by lysine at 26th
position. The affected individuals exhibit no clinical manifestation.

5.7.6 Thalassemia

Definition
Thalassemias are hereditary disorders characterized by impaired synthesis of
polypeptide chains of hemoglobin.

Occurrence
Thalassemia is derived from the Greek word thalassa which means sea. Earlier it
was named as Mediterranean anemia.

• It is more frequently found in population around Mediterranean Sea. It is also
prevalent in India, Central Africa, and West Asia.

• Its highest rate of incidence has been found in Maldives population.

Molecular Changes in Hemoglobin

• Globin molecule has two alpha chains and two beta chains. The alpha chains are
synthesized by two alpha globin genes located on chromosome 16. These have
four alleles which encode alpha globin chains.

88 5 Hemoglobin

• The beta chains are synthesized by one beta globin gene on chromosome 11.
These two alleles encode beta globin chains.

• Mutation in genes is responsible for defective synthesis of globin chains.

Types of Thalassemia
α-Thalassemia

• α-Thalassemia is characterized by partial or complete absence of synthesis
of alpha chains.

• Synthesis of beta chains in adults and gamma chains in new born babies increases
as a compensatory mechanism.

• Increased synthesis of beta chains or gamma chains results into formation of
defective tetrameric structure of hemoglobin. Ultimately, its oxygen carrying
capacity is affected negatively.

β-Thalassemia

• β-Thalassemia is characterized by partial or complete absence of synthesis
of beta chains in hemoglobin.

• As a compensatory mechanism, excessive synthesis of alpha chains occurs. This
forms an alpha chain tetramer which has compromised oxygen-carrying capacity.

Types of β-Thalassemia
β-Thalassemia Minor

• One allele out of a pair is mutant, while allele is normal. It is a heterozygous
condition. Small fraction of beta chain is synthesized.

• Persons are carrier of thalassemia. They remain asymptomatic throughout
life.

β-Thalassemia Major

• Both alleles are mutant. It is a homozygous condition.
• Synthesis of beta chains is completely absent.
• Persons are suffering from severe symptoms. They are inflicted with severe ane-

mia. Their life span is shorter and may die at age of 2 years.

Clinical Manifestations of Thalassemia
Hemolytic Anemia

• There is frequent hemolysis in thalassemia which causes severe anemia. It is
more common in β-thalassemia major.

5.8  Derivatives of Hemoglobin 89

Splenomegaly

• Damaged erythrocytes are removed by the spleen. Its hyperactivity results into
enlargement in size of the spleen.

Infections

• Individuals have compromised immunity. It leads to higher prevalence of bacte-
rial and viral infections among thalassemia patients.

Iron Overload

• Patients need frequent blood transfusions to compensate for anemia. It results
into iron overload. Iron is stored in the liver, skeletal muscles, and heart. It
becomes fatal to life.

5.8 D erivatives of Hemoglobin

Heme moiety interacts with different ligands and forms hemoglobin derivatives.
A few important derivatives of hemoglobin are discussed as follows:

5.8.1 Oxyhemoglobin

• It is binding hemoglobin with oxygen molecule. The binding is reversible and
loose. Hemoglobin can rapidly bind with oxygen at high pressure, and it can
liberate oxygen at low pressure.

• High partial pressure of oxygen favors oxygenation of hemoglobin, and high
partial pressure of CO2 favors deoxygenation of hemoglobin.

• This property of hemoglobin makes it an effective conjugated protein for trans-
port of gases from the lungs to tissues and vice versa.

5.8.2 C arboxyhemoglobin

It is an association of hemoglobin with carbon monoxide. It is also called as
carbonyl-hemoglobin.

• CO is a colorless gas. It is released by incomplete burning of carbonaceous
substances.

• Hb binds with CO as it binds with molecular oxygen. Hemoglobin has 200 times
higher affinity to CO than oxygen molecule. It binds with CO irreversibly and
strongly. CO is fatal to body tissues. It can inhibit cytochrome oxidase enzyme
in electron transport chain.

90 5 Hemoglobin

5.8.3 C arbamino-Hemoglobin
• It is an association between amino group of globin protein and CO2.

Hb.NH2 +CO2 Hb.NHCOOH
(Carbaminohemoglobin)

This is a reversible binding. This property of Hb helps in transport of nearly 10%
of CO2 from tissues to the lungs.

5.8.4 S ulfhemoglobin

• It is an association between hemoglobin and hydrogen sulfide gas. It is a greenish
pigment.

• Excessive accumulation of sulfhemoglobin in blood circulation is described as
sulfhemoglobinemia.

• It results into cyanosis of the skin and mucous membrane. It is caused due to
exposure to sulfur compounds and administration of sulfonamide drugs.

5.8.5 M ethemoglobin

• It is an oxidized form of hemoglobin in which ferrous iron is oxidized into ferric
iron.

• Oxidation of hemoglobin can be caused by exposure to poisons like nitrities,
nitrates, nitrobenzene, antipyrin, aniline dyes, and sulfonamide drugs.

• In healthy individuals, a fraction of methemoglobin (0.3 g/dl) which represents
around 1.5% of total hemoglobin is found.

• Methemoglobin in normal persons is converted into hemoglobin by methemo-
globin reductase enzyme. A deficiency of enzyme is accompanied by accumula-
tion of methemoglobin in blood. This inherited disorder is called as familial
methemoglobinemia.

Excessive amount of methemoglobin in blood circulation is described as
methemoglobinemia.

At 10% level of methemoglobin:

• Dyspnea, cyanosis, and change in behavior

At 20–30% level:

• Anxiety, loss of concentration, and headache

At 50% level of methemoglobin:

5.9  Biodegradation of Hemoglobin 91

• Seizures, coma, and death may occur.
Methemoglobin unlike hemoglobin is unable to bind with oxygen.

5.9 B iodegradation of Hemoglobin

Erythrophagocytosis

• The erythrocytes have 120 days life span in the human body. Senile erythrocytes are
removed from the circulation by macrophages of the spleen which is called as grave-
yard of senile erythrocytes. The physiological process of sequestration of senile
erythrocytes by macrophages from circulation is called as erythrophagocytosis.

• The spleen is the main site of erythrophagocytosis. But the liver and bone mar-
row also act as scavenging organs for mature erythrocytes.

• Under normal health condition, turnover (rate of sequestration of senile RBCs
from circulation and rate of release of fresh RBCs into circulation) of erythro-
cytes is around 2 × 106 per second.

Proteolysis of Hb

• Senile erythrocytes have fragile cell membranes. They pass through sinusoidal
spaces of the spleen, and cell membranes are deformed and rupture. Hemoglobin
is released from mature RBCs. Macrophages in the spleen phagocytose hemo-
globin and catalyze proteolysis of hemoglobin into free globin and heme moiety
as in Figs. 5.5 and 5.6.

Fate of Globin

• Globin enters blood circulation, and it is reutilized for synthesis of hemoglobin
in bone marrow.

• Globin is hydrolyzed into constituent amino acids which enter amino acid pool
of the body for reutilization.

Fate of Heme

• Heme is iron-protoporphyrin ring. Heme is acted upon by heme oxygenase
enzyme. The enzyme splits alpha-methene bridge in porphyrin nucleus. Reaction
occurs in presence of molecular oxygen and NADPH2.

• Porphyrin ring opens up at alpha-methene bridge position between pyrrole ring I
and pyrrole ring II. The Fe++ is released and enters iron store of body for reuse.

• Porphyrin is converted into green-colored pigment called as biliverdin with
release of CO and H2O. The coenzyme is oxidized into NADP+.

92 5 Hemoglobin

SENILE RBCS
sequesterated
in SPLEEN, Born Marrow

HEMOLYSIS

Rupture of cell membrane
Hemoglobin liberated

Hemoglobin within SPLEEN, Born Marrow
Hydrolysis

Globin Release of HEME
Proteolysis Globin
O2
Reutilization NADPH2 Acted upon by
of
NADP+ Heme – ∝ – Metheyl oxygenase
Globin in erythropoiesis ( Found in R.E. Cells)

Release Oxidative splitting
of of Iron - Porphyrin ring

Constitutent A+ ∝ Methyne Bridge [ Between
Amino [ Pyrrole
acids
Co [ ring I & II

Opening of Ring

Enter Formation of R.E.Cells
Amino acid Biliverdin

Pool

Fe++ Iron bilirubin NADPH2
Reused Released reductase NADP+

Bilirubin

Fig. 5.5  Biodegradation of hemoglobin

Reduction of Biliverdin

• Within macrophages, biliverdin is reduced into yellow-colored pigment called as
bilirubin. Reaction is catalyzed by bilirubin reductase enzyme in the presence of
coenzyme NADPH2 as in Figs. 5.5 and 5.6.

5.9  Biodegradation of Hemoglobin 93

Fate of Bilirubin

Formation of bilirubin
in spleen, bone marrow

Blood
circulation

Enters liver Bilirubin
Lipid soluble
Bilirubin Glucuronyl
Glucuronic transferase Binds with albumin to form
Bilirubin-albumin
acid complex
Enters
Bilirubin systemic
diglucuronide circulation
(direct bilirubin) Indirect bilirubin

Urobilinogen enters
(5%) systemic circulation

Kidney

Urobilinogen Enterohepatic
circulation

Bilirubin Reabsorbed Urobilinogen
diglucuronide from ileum
(70-80%) Excreted
Bilirubin
diglucuronide Reduced into stercobilinogen Oxidized into
Colon Bacteria (20%) oxidized Urobilin
Deconjugates Stercobilin

bilirubin Stool (50-100mg/day)
Diglucuronide

Bilirubin

Urobilinogen

Fig. 5.6  Fate of bilirubin

94 5 Hemoglobin

Fate of Bilirubin

• Bilirubin from the spleen enters blood circulation. This bilirubin is lipid soluble
and is called as indirect bilirubin. It combines with albumin, and it is distributed
as bilirubin-albumin complex.

• Within the liver, bilirubin-albumin complex enters liver sinusoidal spaces. The
membranes of hepatocytes have bilirubin receptors, and bilirubin from complex
attaches to receptors. Albumin is released into circulation.
–– Within smooth endoplasmic reticulum of hepatocytes, bilirubin under-
goes conjugation with two molecules of glucuronic acids. Reaction is cata-
lyzed by glucuronyl transferase enzyme. There is transfer of glucuronic acid
moiety from active nucleotide (UDP-Ga) to carboxylic group of propionic
acid in bilirubin to form glucuronide. Bilirubin diglucuronide is formed
which is water soluble and is called as direct bilirubin or conjugated bilirubin
as in Fig. 5.6.

• Bilirubin is secreted in the bile. It enters the duodenum and reaches the colon.
Bacteria in the colon secrete beta-glucuronidase enzyme which deconjugates
bilirubin diglucuronide. Free bilirubin is released in the colon.

• Bilirubin undergoes a series of reduction reactions to form dihydrobiliru-
bin  →  meso-bilirubin  →  l-stercobilinogen (colorless compound) as in
Fig. 5.6.

• About 25% of l-stercobilinogen is excreted in stool. It undergoes auto-oxidation
in air and is converted into yellowish brown pigment called as stercobilin.
Another 60–70% of l-stercobilinogen is reabsorbed from the intestine and enters
hepatic portal vein. It reaches the liver for secretion into the bile. It is called as
enterohepatic circulation. A small fraction of l-stercobilinogen (5%) escapes
enterohepatic circulation and enters systemic circulation and reaches kidneys. It
is called as urobilinogen and excreted in urine. On exposure to air, it is oxidized
into l-urobilin which imparts yellow color to urine.

5.10 Biosynthesis of Hemoglobin

It can be described under two stages as follows:

• Biosynthesis of globin
• Biosynthesis of heme

5.10.1 B iosynthesis of Heme

Heme is iron-containing protoporphyrin IX compound. Heme is synthesized in
normoblasts.

5.10  Biosynthesis of Hemoglobin 95

The different steps explaining heme synthesis are described as follows:

Synthesis of δ-Amino Levulinic Acid (ALA)

This step occurs in mitochondria:
• A molecule of succinyl CoA undergoes condensation with glycine to form

δ-amino levulinic acid.
• Reaction is catalyzed by δ-amino levulinic acid synthase enzyme in presence of

pyridoxal phosphate as coenzyme. Reaction occurs in two steps as follows:
–– In the first step, there is formation of alpha-ketoadipic acid and release of

CoA-SH.
–– In the second step, there is formation of delta ALA with release of a molecule

of CO2.
–– Both steps are catalyzed by ALA synthase enzyme with pyridoxal phosphate

as coenzyme.
–– Deficiency of pyridoxal P results into failure of ALA formation and interferes

in heme synthesis. It is cause of anemia.
• ALA synthase is mitochondrial enzyme. It is a rate-limiting step of heme synthe-

sis as in Fig. 5.7.

Synthesis of Porphobilinogen (PBG)

This step occurs in cytoplasm:
• Two ALA molecules undergo condensation to form porphobilinogen with

removal of a molecule of water.
• Reaction is catalyzed by ALA dehydratase enzyme. Enzyme requires zinc ions

as cofactor.

Synthesis of Uroporphyrinogen (UPG)

This step occurs in cytoplasm:
• Four molecules of porphobilinogen condense together to form uroporphyrinogen

with loss of four molecules of ammonia.
• Reaction is catalyzed by PBG deaminase or uroporphyrin I synthase.
• Uroporphyrinogen is a linear tetrapyrrole and called as hydroxy methyl

bilane (HMB). The HMB undergoes spontaneous cyclization to form uropor-
phyrinogen I.
• Uroporphyrinogen I is changed into uroporphyrinogen III by enzyme uroporphy-
rinogen III synthase enzyme as in Fig. 5.7.

96 5 Hemoglobin

ALA Synthase Mitochondria
Pyridoxal P alpha-keto Adipic acid

Succinyl CoA + Glycine

CoA.SH

ALA Synthase/Pyridoxal P Mitochondria

alpha-keto Adipic acid delta-amino Levulinic acid (ALA)

CO2 Cytosol
ALA Dehydratase

(2 mole) Delta-ALA Porphobilinogen (PBG)

2 H2O Cytosol
PBG deaminase

(4 mole) Porphobilinogen Uroporphyrinogen III (UPG)

(4 mole) NH3 Cytosol
UPG Decarboxylase

Uroporphyrinogen III Coproporphyrinogen III (CPG)

(4 mol) CO4 Mitochondria
CPG Oxidase

Coproporphyrinogen III Protoporphyrinogen III (PPG)
CO2 NADP+ NADPH2

Protoporphyrinogen III PPG Oxidase Mitochondria
4 hydrogen ions Protoporphyrin III

Heme Synthase Mitochondria
Heme
Protoporphyrin III

Fig. 5.7  Showing synthesis of HEME

Synthesis of Coproporphyrinogen (CPG)

This step occurs in cytoplasm:
• Uroporphyrinogen III undergoes decarboxylation to form coproporphyrinogen

with loss of four molecules of CO4.

5.10  Biosynthesis of Hemoglobin 97

• Reaction is catalyzed by uroporphyrinogen decarboxylase enzyme.
• Acetate groups in uroporphyrinogen are decarboxylated into methyl groups as in

Fig. 5.7.

Synthesis of Protoporphyrinogen III (PPG)

This step occurs in mitochondria:
• Coproporphyrinogen undergoes oxidation in mitochondria to form protoporphy-

rinogen III.
• Reaction is catalyzed by coproporphyrinogen oxidase (enzyme exhibits series III

specificity).
• Propionic acid side chains decarboxylated in presence of molecular oxygen to

form vinyl groups as in Fig. 5.7.

Synthesis of Protoporphyrin (PP)

This step occurs in mitochondria:
• Protoporphyrinogen III undergoes oxidation to form protoporphyrin.
• Reaction is catalyzed by protoporphyrinogen oxidase.
• Methylene bridges (-CH2) converted into methenyl bridges (–CH〓).
• This formation of protoporphyrin IX as in Fig. 5.7.

Synthesis of Heme

This step occurs in mitochondria:
• In the last stage, ferrous iron is attached to protoporphyrin IX in mitochondria.
• Reaction is catalyzed by heme synthase (ferrochelatase) enzyme. It is located in

mitochondria.
• Ferrous form (Fe++) of iron in heme imparts red color to heme moiety.

However, presence of ferric iron (Fe+++) in heme converts it into hematin
moiety. It imparts brown color to hematin moiety.
• This property is in utilized in Sahli’s hemoglobinometer for assaying hemo-
globin concentration.

5.10.2 Biosynthesis of Globin

Globin molecule is made up of two alpha chains and two beta chains. Their synthe-
sis is regulated by globin genes located on chromosome 16 and chromosome 11,
respectively. The expression of alpha genes and beta genes is well controlled.

98 5 Hemoglobin

ZETA 2 5’
ZETA 1
MU
CHROMOSOM 16 Psudo T
Alpha - 1 R
A
Alpha 2 TRANSCRIPTION N ALPHA
Alpha 1 mRNA S CHAINS
L
THETA A
3’ T
I
O
N

ALPHA - GLOBIN
GENE CLUSTURE

Fig. 5.8  Alpha globin genes

Alpha Globin Genes

• Single chromosome 16 contains two alpha globin genes. Overall, two chromo-
somes 16 have 4 alpha globin genes.

• Four alpha globin genes regulate synthesis of two alpha polypeptide chains.
• Alpha globin gene has seven gene loci. They are named as zeta1, zeta 2, mu,

pseudo alpha 1, alpha 2, alpha 1, and theta in 5′ → 3′ direction as in Fig. 5.8
• Alpha gene cluster transcribe mRNA which directs synthesis of alpha globin

chains.

Beta Globin Genes

• Each chromosome 11 contains single beta globin gene.
• Two beta globin genes in two chromosomes 11 regulate synthesis of beta poly-

peptide chains.
• Beta gene has five gene loci and is called as beta gene cluster. They are named

as epsilon, gamma G, gamma A, delta, and beta in 5′  →  3′ direction as in
Fig. 5.9
• Beta gene transcribes mRNA which controls synthesis of beta chains in adults.

5.10  Biosynthesis of Hemoglobin 99

5’ BETA
EPSILON CHAINS

GAMMA GCHROMOSOM 11 T
GAMMA A R
TRANSCRIPTION A
DELTA mRNA N
S
BETA L
3’ A
BETA - GLOBIN T
GENE CLUSTURE I
Fig. 5.9  Beta-globin genes O
N

SYNTHESIS OF β-GLOBIN

5.10.3 Regulation of Heme Biosynthesis

ALA Synthase

• It is a chief regulatory enzyme in heme biosynthesis. It is a rate-limiting enzyme.
Its activity is influenced by following compounds as:
–– Hematin is formed in the body from surplus ferrous iron. It is oxidized into
ferric state to form hematin. It acts as allosteric inhibitor to ALA synthase.
–– High concentration of glucose in cells inhibits synthesis of enzyme ALS
synthase.
–– Heme prevents synthesis of enzyme ALA synthase through negative feedback
mechanism.

Lead
• Lead inhibits ALA dehydratase enzyme and regulates heme synthesis.

Isonicotinic Acid Hydrazide (INH)

• Prolonged intake of antitubercular drug, INH, leads to deficiency of pyridoxal
phosphate. It is necessary for synthesis of δ-ALA.

100 5 Hemoglobin

Barbiturates
• Drugs like barbiturates are metabolized by heme-containing cytochrome P450

enzyme in the liver. They induce synthesis of heme.

Covalent Bond
• A bond formed by sharing of electrons between two atoms.

Coordinate Bond
• A bond formed by donating a pair of electrons by one atom called as donor atom.

Suggested Readings

Adamson JW, Finch CA (1975) Hemoglobin function, oxygen affinity and erythropoietin. Annu
Rev Physiol 37:351

Bunn HF (1981) Hemoglobin: structure and function. In: Beck WS (ed) Hematology. MIT Press,
Cambridge

Ganong WF (2003) Review of medical physiology, 21st edn. Lange Medical Book, New York
Wallerstein RO (1987) Laboratory evaluation of anemia. West J Med 146:443

Carbohydrates 6

6.1 D efinition

Carbohydrates are polyhydroxy aldehydes or ketones or compounds which yield poly-
hydroxy aldehydes and ketones upon hydrolysis.

Carbohydrates are organic biomolecules abundantly distributed in animals and
plants. In humans, glucose and glycogen forms of carbohydrates serve as an instant
and important source of energy for physiological activities. Highly specific carbo-
hydrates like ribose, lactose, and galactose serve as structural components of nucleic
acid, lipids, and breast milk.

6.2 C lassification

Carbohydrates are classified into four main categories as follows:

1 . Monosaccharides
2 . Disaccharides
3. Oligosaccharides
4 . Polysaccharides

6.2.1 M onosaccharides

• The word “saccharide” is derived from the Greek word “sakkharon” which
means “sugar” or “sweet.”

• Monosaccharides are simple sugars. They are the carbohydrates which can-
not be hydrolyzed into more simple sugars.

• Their molecular formula is [CnH2nOn).
Examples: Glucose, fructose, galactose, ribose, erythrose

© Springer Nature Singapore Pte Ltd. 2019 101
A. Gupta, Comprehensive Biochemistry for Dentistry,
https://doi.org/10.1007/978-981-13-1035-5_6

102 6 Carbohydrates

Classification of Monosaccharides
Monosaccharides can be further subdivided on the basis of two criteria as

follows:

• On the basis of number of carbon atoms

–– Monosaccharides can be trioses, tetroses, pentoses, hexoses, and heptoses.
• On the basis of functional group

–– Monosaccharides containing aldehyde (–CHO) group are called as
“aldoses” and those containing ketone (–CO) group are called as
“ketoses.”

Number of carbon atom Aldoses Ketoses
Trioses Dihydroxyacetone phosphate
Tetroses Glyceraldehyde Erythrulose
Pentoses Erythrose Ribulose, xylulose
Hexoses Ribose, arabinose, xylose Fructose
Heptoses Glucose, galactose, mannose Sedoheptulose
Glucoheptose, galactoheptose

6.2.2 D isaccharides

• They are the carbohydrates which yield two molecules of similar or dissimilar

monosaccharides upon hydrolysis.

• Their molecular formula is [Cn(H2O)n–1].
• Example:

They are the carbohydrates which yield two molecules of similar or dissimilar
monosaccharides upon hydrolysis.
Their molecular formula is [Cn(H2O)n–1]
Example:

Sucrose Glucose + Fructose

Lactose Glucose + Galactose

Lactulose Galactose + Fructose

Maltose Glucose + Glucose
Isomaltose Glucose + Glucose
Trehalose Glucose + Glucose

Cellobiose Glucose + Glucose

6.2.3 O ligosaccharides

• They are the carbohydrates which yield three to ten monosaccharide units upon
hydrolysis.

• Example:

6.3  Characteristics of Monosaccharides 103

They are the carbohydrates which yield 3-10 monosaccharide units upon hydrolysis.
Example:

Trisaccharides

• Raffinose Glucose + Galactose + Fructose

• Maltotriose 3(Glucose)

Tetrasccharides

• Stachyose [Glucose + 2(Galactose) + Fructose]
Pentasaccharides

• Verbascose [Glucose + 3(Galactose) + Fructose]

6.2.4 P olysaccharides

• They are the carbohydrates which yield more than ten monosaccharide units
upon hydrolysis.

• Polysaccharides are also called as glycans.
• Their molecular formula is [C6H10O5]n.
• Depending on nature of hydrolytic products, polysaccharides are of two types as

follows:
–– Homopolysaccharides (Homoglycans)

These polysaccharides yield similar monosaccharide units upon hydrolysis.
Example: Starch, glycogen, inulin, cellulose
–– Heteropolysaccharides (Heteroglycans)
These polysaccharides yield dissimilar monosaccharide units upon hydrolysis.
Example: Hyaluronic acid, heparin, chondroitin sulfate, keratan sulfate

6.3 C haracteristics of Monosaccharides

Monosaccharides exhibit characteristic features which are described as follows:

6.3.1 Asymmetric Carbon Atom

• When four dissimilar atoms or groups are attached to a carbon atom, it is called
as asymmetric carbon atom or “chiral carbon.”

• Monosaccharides contain asymmetric carbon atoms.
• Asymmetric carbon is responsible for isomerism in monosaccharides as in Fig. 6.1.

6.3.2 V ant Hoff’s Rule of “n” for Number of Isomers

• According to Vant Hoff’s rule of “n.”
–– The number of isomers in a compound depends on the number of asymmetric
carbon atoms in that compound.

104 6 Carbohydrates

• The “n” represents number of asymmetric carbon atoms.
• Number of isomers in any monosaccharide is given by 2n.
• Aldohexose (glucose) has four asymmetric carbon atoms at positions C2, C3,

C4, and C5. So it has 16 isomers (2x2x2x2=16). Ketohexose (fructose) has three
symmetric carbon atoms at positions C3, C4, and C5. So it has eight isomers
(2x2x2=8). All isomers are not biologically active in body tissues.

6.3.3 Isomerism in Monosaccharides

Definition
Isomerism is defined as a phenomenon in which compounds having similar molecu-

lar formula exhibit difference in their chemical structures.

• The word Isomerism is derived from Greek word and it conveys (‘isos means
equal and meros means parts). Monosaccharides exhibit isomerism as

described below:

1 . Stereoisomerism
Stereoisomerism is a type of isomerism in which compounds have similar

molecular formula, but they differ in relative arrangement of atoms or groups

in three-dimensional space.

• Monosaccharides show stereoisomerism.
Example: Glucose exhibit two forms as d-glucose and l-glucose. These ste-
reoisomers differ in arrangement of H and OH groups on C5 atom in glucose
molecule. The C5 atom in glucose molecule is called as “reference carbon atom”
or “penultimate carbon atom” as in Fig. 6.2.

Fig. 6.1 Asymmetric CHO
Carbon atom H C OH

R

Fig. 6.2 Stereoisomerism OO
in glucose
1C H 1C H

H 2C OH OH 2C H

HO 3C H PENULTIMATE H 3C OH
H 4C OH CARBON HO 4C H

H 5C OH HO 5C H

6CH2OH 6CH2OH
D - GLUCOSE L - GLUCOSE

6.3  Characteristics of Monosaccharides 105

• Reference or penultimate carbon is the carbon atom adjacent to the last pri-
mary alcohol carbon in a compound. It determines “d” or “l” series of com-
pounds. In d-glucose, OH group is located on right-hand side in C5 carbon atom.
In l-glucose, position of OH group is reversed in C5 carbon atom as in Fig. 6.2.

• Aldohexose exhibits 16 stereoisomers. They exist in “d” and “l” series. There
are eight d-aldohexoses as d-allose, d-altrose, d-idose, d-talose, d-gulose, d-­
glucose, d-galactose, and d-mannose. There are eight l-aldohexoses as
enantiomers.

2. Enantiomers
The stereoisomers that are nonsuperimposable and mirror image of each other.

Example: d-Glucose and l-glucose are mirror images and nonsuperimpos-

able molecules. So they are called as enantiomers as in Fig. 6.2.

• D series of sugars are predominant in nature. Only D sugars are metabolically
active in the human body. Out of 16 stereoisomers, only d-glucose, d-galactose,
and d-mannose exist commonly in nature.

3 . Epimers
Epimers are the isomers which differ from each other in the arrangement of atoms

or groups around a single chiral carbon.

• Example: d-Glucose and d-galactose differ around C4 atom. d-Glucose and
d-mannose differ around C2 atom as in Fig. 6.3.

• The process of conversion of one epimer into another in body tissues is called as
epimerization. In the liver, galactose is converted into glucose by epimerase
enzyme.

4 . Anomers
Anomers are defined as the cyclic monosaccharides which differ from each other

in the arrangement of atoms or groups around C1 atom in aldoses and C2 atom in
ketoses.

Fig. 6.3 Epimers CHO CHO CHO
H C OH H C OH HO C2 H
HO C H HO C H HO C H
H 4C OH HO C4 H
H C OH H C OH H C OH
H C OH
CH2OH CH2OH
D - GLUCOSE D - GALACTOSE CH2OH
D - MANNOSE

106 6 Carbohydrates

• Chiral carbon in anomers is called as “anomeric carbon.”
• Anomers are cyclic epimers as in Fig. 6.4.

Example:
–– d-Glucose exhibits two anomers, namely, α-d-glucose and β-d-glucose. In

α-d-glucose, OH group is below the plane of molecule.
In β-d-glucose, OH group is above the plane of molecule.

6.3.4 Optical Isomerism

Asymmetric carbon atom confers optical activity to a compound. When a plane
polarized light passes through a monosaccharide solution, it rotates the light beam
either to right or left depending. The phenomenon is called as optical isomerism.
Accordingly, a monosaccharide is called as “dextrorotatory” and “levorotatory.”

• The dextrorotatory glucose molecule is represented as (d-glucose) or (+) glu-

cose, and levorotatory glucose is represented as (l-glucose) or (−) glucose.
• The notations “d” and “d” represent stereoisomer and optical isomer.

Example: d-Glucose is (+) or dextrorotatory. It means a glucose molecule
with OH group on the right-hand side on C5 carbon atom can rotate a plane
polarized light in right-hand direction. Another example is d-fructose is (−)
or levorotatory.

CH2OH

HC CH

C H H 1C
OH C OH

OH C CH2OH
5C
H OH H OH H
α-D-GLUCOPYRANOSE 4C H 1C
OH OH H
2C O
3C
CH2OH

HC C OH H OH
GLUCOSE [HAWORTH PROJECTION]
H H 1C
C OH CH

OH C

H OH
β-D-GLUCOPYRANOSE

Fig. 6.4  Haworth projection of glucose (anomers)

6.4  Biologically Important Carbohydrates 107

6.3.5 R acemic Mixture

It is a mixture which contains equal amount of dextrorotatory and levorotatory iso-
mers of a compound.

• Racemic mixture is represented with prefix (±)- or (dl). A racemic mixture is
inactive optically. Its net optical rotation is zero.

6.4 Biologically Important Carbohydrates

6.4.1 Monosaccharides

1. Trioses
• Important trioses like d-glyceraldehyde and dihydroxyacetone phosphate are
the important intermediate metabolites in glycolysis cycle. They are con-
verted into glycerol which is a structural constituent of lipids.

2 . Tetroses
• Erythrose 4-phosphate is an intermediate metabolite in hexose monophos-
phate shunt. It is a precursor for biosynthesis of tryptophan, phenylalanine,
and tyrosine amino acids.

3. Pentoses
• d-Ribose is a structural residue of RNA, NAD, FAD, and coenzyme A.
• d-2-Deoxyribose is a structural residue of DNA molecule.
• d-Ribulose and d-xylulose are intermediate metabolites in HMP shunt.
• l-Xylulose is a marker in hereditary disorder called as “pentosuria.” It accu-
mulates in the urine of patient.

4 . Hexoses
• d-Glucose
–– d-glucose is a colorless and crystalline monosaccharide. It is readily solu-
ble in water.
–– It exists in nature in free state in fruits like grapes. It is found in bound
state in cellulose, maltose, and mucopolysaccharides. It is called as
grape sugar.
–– It is the physiologically active sugar present in the human body. Normal
blood glucose level is between 80 and 120 mg/dl under fasting state.
–– Glucose is the chief source of energy for body tissues. Brain cells and
erythrocytes utilize glucose exclusively for their energy demand.
–– Glucose is stored in the liver and skeletal muscles in the form of
glycogen.
–– d-Glucose is dextrorotatory and also called as “dextrose.”
–– It is a reducing sugar.

108 6 Carbohydrates

–– It forms glucosazone crystals. Their shape resembles cluster of yellow
needles.

• d-Galactose
–– It exists in bound form in nature. Galactose is a structural component of
mucopolysaccharides, glycoproteins, and compound lipids.
–– It is a structural unit of lactose. In mammary glands, glucose is epimerized
into galactose.
–– d-Galactose is dextrorotatory.
–– It is a reducing sugar.
–– It forms galactosazone crystals. Their shape resembles rhombic plates.

• d-Fructose
–– It is found mainly in fruits and honey. It is called as fruit sugar.
–– It is a colorless and crystalline ketohexose.
–– It is a structural unit of sucrose.
–– It is sweeter than sucrose.
–– d-Fructose is levorotatory and is also called as “levulose.”
–– d-Fructose exhibits anomerism. The C2 atom in d-fructose is anomeric,
and it forms two anomers, namely, α-d-fructose and β-d-fructose.
–– It is a reducing sugar.
–– It forms glucosazone crystals. Their shape resembles cluster of yellow
needles.

• d-Mannose
–– It is not an essential sugar in the human body. It is biosynthesized from
glucose by epimerization.
–– It was extracted from plant “mannans.”
–– It is a structural unit of glycoproteins in the human body.
–– It forms glucosazone crystals. Their shape resembles cluster of yellow
needle-shaped crystals.

5 . Heptoses
• Sedoheptulose
–– It is one of the few heptoses existing in nature. It is found in plants of
sedum family.
–– Sedoheptulose 7-phosphate is an intermediate metabolite in HMP shunt.

6.4.2 Disaccharides

Three disaccharides are biologically important. These are as follows:

6.4  Biologically Important Carbohydrates 109

1. Lactose
• Lactose is called as “milk sugar.”
• It is a reducing disaccharide.
• It is composed of d-glucose and d-galactose. These are linked together by
beta-1,4 glycosidic bond as in Fig. 6.5.
• It forms lactosazone crystals. Their shape resembles cotton ball or hedge-
hog as in Fig. 6.10.

2. Maltose
• It is commonly called as malt sugar.
• It is a colorless and sweet monosaccharide with crystalline structure.
• It is composed of two molecules of d-glucose linked by alpha-1,4 glycosidic
bond as in Fig. 6.6.
• It is a reducing disaccharide.
• In the human body, maltose is produced by enzymatic hydrolysis by amylase
on dietary starch.

Fig. 6.5 Lactose CH2OH CH2OH

HO 5 OH O OH
H 1 O 4H

4

H3 2H 3 2H
β-D-GaLACTOSE D-GLUCOSE

Fig. 6.6 Maltose CH2OH CH2OH
5 H5
OH OH

4 14 1

32 O 3 2 OH
α-D-GLUCOSE α-D-GLUCOSE

110 6 Carbohydrates

• Maltose is hydrolyzed into two glucose moieties by maltase in the gut.
• It forms maltosazone crystals. Their shape resembles sunflower petals as

in Fig. 6.10.

3 . Sucrose
• It is commonly called as table sugar or cane sugar as it is present in
sugarcane.
• It is a colorless and crystalline disaccharide. It is readily soluble in water. It is
sweet in taste.
• It is composed of d-glucose and d-fructose linked by alpha-d-glucosyl-beta-
d-­fructoside (alpha-1,2) linkage as in Fig. 6.7.
• Aldehyde and ketone functional groups are linked together in sucrose.
It is a nonreducing disaccharide. There is absence of free functional
group.
• It does not form osazone.
• Sucrose does not show mutarotation as both anomeric carbons are linked
together.
• Sucrose exhibits dextrorotation (+62.5°). Its hydrolytic residues are glucose
and fructose. Glucose has dextrorotation (+52.5°), while fructose shows levo-
rotation (−92°). Therefore, the hydrolytic residues invert the optical rotation.
So the mixture has more levorotation than dextrorotation, and it is called as
“invert sugar.” The enzyme which hydrolyzes sucrose is called as invertase or
sucrose.
Example: Honey contains invert sugar and fructose.

Fig. 6.7 Sucrose CH2OH CH2OH
O
5 OH H
4
1 25
3 2 O 3 4 CH2OH

α-D-GLUCOSE α-D-GLUCOSE

6.4  Biologically Important Carbohydrates 111

6.4.3 Polysaccharides (Glycans)

H omopolysaccharides
Homopolysaccharides are the polymers of the same monosaccharide. They yield the
same monosaccharide units on hydrolysis. They are also called as “homoglycans.”

Starch
Occurrence
Starch is synthesized by green plants as a reserve food material. It is found in differ-
ent parts of plants like leaves, stem, roots, and fruits. Staple foods, namely, potato,
rice, wheat, maize, and cassava, are rich source of starch. Starch is the most com-
mon dietary source of energy for humans.

Characteristics and Chemical Composition

• Starch is a white, odorless, and crystalline polymer of d-glucose.
• It is poorly soluble in cold water. Upon heating, starch powder swells up in water

and forms gel-like mass.
• Starch gives deep blue color with iodine solution. It is not a reducing

carbohydrate.
• Starch is made up of amylose and amylopectin. They are polymers of d-­

glucose residues. They have different structures and properties.
• Amylose

Amylose represents about 20% of starch by weight. It has molecular weight
around 60,000. Amylose is soluble in water. It shows deep blue color with iodine
solution. Amylose is a linear polymer of around 300 d-glucose residues. They
are linked by alpha-1 → 4 glycosidic bonds.
• Amylopectin
Amylopectin represents about 80% of starch by weight. It has molecular weight
around 500,000–600,000. It is insoluble in water. It swells up in water and forms
gel-like mass. It shows reddish violet color with iodine solution as in Fig. 6.8.
Amylopectin is a greatly branched polymer of d-glucose residues. Main trunk
and branches of amylopectin have d-glucose residues linked by alpha-1 → 4 gly-
cosidic bonds. A branch of d-glucose residues is linked to the main trunk by
alpha-1 → 6 glycosidic bond. After every 25 d-glucose residues, a branch is pres-
ent, and around 70–80 branches are present in amylopectin molecule.

112 6 Carbohydrates

GGG
α-1→6 - BONDING

GGGGGGGG GG

α-1→4 - GLYCOSIDIC BOND

Fig. 6.8 Amylopectin

Hydrolysis of Starch

• By Action of Alpha-Amylase
Alpha-amylase is found in saliva and pancreatic juice. Salivary amylase acts at
optimum (pH 6.7), and pancreatic amylase acts at optimum (pH 7.1). The alpha-­
amylase cleavages alpha-1  →  4 glycosidic bonds randomly within starch
molecule.
In the initial stage, enzymatic hydrolysis yields “amylodextrin.” It shows violet
color with iodine solution. Further hydrolysis of starch yields “erythrodextrin”
which shows red color with iodine solution. More hydrolysis of starch yields
“achrodextrin” which does not give any color with iodine solution. Finally, enzy-
matic hydrolysis yield maltose.
Alpha-amylase hydrolysis of starch yields a mixture of maltose and a few
residues of dextrin.

• By Action of Beta-Amylase
Beta-amylase is found in sprouted seeds, germinated cereals (called as malt), and
almond. Beta-amylase starts cleavage of alpha-1  →  4 glycosidic bonds from
nonreducing end of starch molecule. Beta-amylase cannot cleavage alpha-1 → 6
glycosidic bonds at branch points in starch. It results into formation of limit
dextrin.
Beta-amylase hydrolysis of starch yields a mixture of maltose and limit dex-
trin. Limit dextrin is a large residual polymer of d-glucose residues which is
produced during beta-amylase hydrolysis of starch. It cannot be further
hydrolyzed.

6.4  Biologically Important Carbohydrates 113

Functions of Starch

• Starch is the dietary source of energy for humans and higher animals. In the
body, starch is hydrolyzed into maltose and ultimately into glucose.

Glycogen
Occurrence

• Glycogen is the chief reserve food of animal kingdom. Glycogen is stored in the
liver and skeletal muscles in humans and higher animals.

• Glycogen is analogous to starch in plants. So glycogen can be called as “animal
starch.”

• Some fungi, yeast, and bacteria also possess glycogen in their body.

Characteristics and Chemical Composition

• Glycogen is a white, odorless, and crystalline polymer of d-glucose.
• It is poorly soluble in water and forms an opaque solution.
• Its molecular weight ranges from 1,000,000 to 5,000,000.
• It shows deep red color with iodine solution.
• Glycogen is a highly branched polymer of d-glucose residues. The main trunk of

glycogen molecule is made up of d-glucose residues linked by alpha-1 → 4 gly-
cosidic bonds. Branches of d-glucose residues are linked to the main trunk by
alpha-1 → 6 glycosidic bonds as in Fig. 6.9. After every 15 glucose residues, a
branch is present.
• Molecular structure of glycogen is more complex than amylopectin.

Fig. 6.9 Glycogen Branches

α - 1→ 6 - bonding

Glucose Main stem
moieties α - 1→ 4 - bonding

Branched chain glycogen structure

114 6 Carbohydrates

Functions of Glycogen

• Glycogen is the stored food for animals. It is converted into glucose by glycoge-
nolysis in the liver and skeletal muscles in humans. Glucose is utilized by body
tissues for fulfilling energy demand.

Inulin
Occurrence

• Inulin is found in plants like onion, garlic, dahlia, and dandelion. It is a reserve
food of plants.

Characteristics and Chemical Composition

• It is a white, odorless, and crystalline polymer of d-fructose.
• Its molecular weight is 5000.
• It does not give color with iodine solution.
• Inulin is made up of d-fructose residues linked by beta-(1 → 2) glycosidic bonds.
• Inulin is hydrolyzed by inulinase enzyme present in plant tissues.

Functions of Inulin

• Inulin is not metabolized in the human body. Inulin does not have any nutritional
value for humans.

• Inulin is used to estimate glomerular filtration rate (GFR). It is an indicator of
renal function.

• Inulin is used to estimate proportion of extracellular fluid (ECF).

Needle shaped Sun flower shaped Cotton shaped
crystals crystals crystals

[Glucosazones] [Maltosazone] [Lactosazone]

Fig. 6.10 Osazones

6.4  Biologically Important Carbohydrates 115

Cellulose
Occurrence

• Cellulose is the abundantly found organic substance on earth.
• It constitutes 95% of cotton and 55% of wood.
• Cellulose is the main structural constituent of cell wall of green plants.
• It is also found in cell wall of a few algae and water molds.

Characteristics and Chemical Composition

• It is a white, odorless, and crystalline polymer of d-glucose.
• It is hydrophilic but insoluble in water.
• Its molecular weight ranges from 27,000 to 900,000.
• Cellulose is a linear chain polymer composed of d-glucose residues linked by

beta-(1  →  4) glycosidic bonds. The number of d-glucose residues is variable.
Cellulose polymers in cotton and wood are made up of around 10,000 residues
and 2000 d-glucose residues, respectively.
• When cellulose is treated by mineral acids, it results into formation of “cellobi-
ose.” It is a reducing disaccharide. It is made up of two units of d-glucose linked
by of beta-(1 → 4) glycosidic bonds.

Functions of Cellulose

• Humans consume cellulose along with vegetables and fruits. It is not digested in
the human body. It is due to absence of cellulose-digesting enzyme among
humans.

• Cellulose does not have any nutritional value for humans.
• Cellulose has roughage value for humans. Ingestion of cellulose in the form of

vegetables and fruits increases contents of the large intestine. Distension of the
intestine stimulates peristalsis and helps in evacuation of bowels. It relieves
constipation.
• Cellulose is digested by termites and ruminants. Termites possess Trichonympha
in the gut, and ruminants harbor anaerobic bacteria in the large intestine. These
microbes help in digestion of cellulose by action of cellulase enzyme.

Dextran
Occurrence

• Dextran was initially discovered by microbiologist Louis Pasteur in wine. It is
synthesized from sucrose by action of Gram-positive cocci named as Leuconostoc
mesenteroides. These organisms induce polymerization of glucose residues in
sucrose and result into formation of dextran.

116 6 Carbohydrates

Characteristics and Chemical Composition

• It is a colorless, odorless, and crystalline polymer of glucose.
• It is readily soluble in water.
• Its molecular weight ranges from 1,000,000 to 2,000,000.
• Dextran is a neutral polymer and exhibits high colloidal osmotic pressure.
• Dextran is a highly branched chain polymer of d-glucose residues. There is

alpha-(1 → 6) glycosidic linkage between d-glucose residues in straight chain.
The branch points are attached by alpha-(1 → 3) linkage.

Functions of Dextran

• Dextran is not metabolized in the body.
• Dextran is used as plasma expander. It is infused intravenously and dextran

remains in blood vessels for hours. It helps to increase volume of plasma. It is
useful to manage hypovolemia due to acute blood loss when blood transfusion is
not possible.
• Dextran is a relatively safe intravenous fluid. However, its use is associated with
side effects like anaphylaxis, acute renal failure, and difficulty in blood grouping
and cross matching.

H eteropolysaccharides (Heteroglycans)
Heteropolysaccharides are of polymers of different monosaccharides. They yield
mixture of monosaccharide units on hydrolysis. They are also called as
“heteroglycans.”

This group of glycans is structurally associated with amino sugars and uronic acid.
Therefore, they were described by “Jeanloz” as “glycosaminoglycans” (GAGs).

These heteropolysaccharides are characterized by formation of slimy and vis-
cous solution. So they are called as “mucopolysaccharides.”

6.5 C lassification of Mucopolysaccharides

6.5.1 Acidic and Non-sulfated Mucopolysaccharides

H yaluronic Acid
Occurrence

• It is found in synovial fluid in joints, vitreous humor of the eye, epithelial tissues,
connective tissues, brain tissues, and umbilical cord.

Characteristics and Chemical Composition

• It is an acidic mucopolysaccharide at body pH.
• Its molecular weight is around 5,000,000.

6.5  Classification of Mucopolysaccharides 117

• Hyaluronic acid exists in free state and in bound state with proteins. It forms a
viscous gel with proteins which is a component of extracellular matrix.

• Hyaluronic acid is a polymer of d-glucuronic acid and N-acetyl glucosamine
(NAG) residues. These residues are linked by beta-(1  →  3) and beta-(1  →  4)
glycosidic linkages.

• Upon hydrolysis, it yields equimolar proportion of d-glucuronic acid, N-acetyl
glucosamine, and acetic acid in solution.

Functions of Hyaluronic Acid

• Hyaluronic acid is an integral structural component of extracellular matrix in
tissues.

• It acts as cementing substance in body tissues.
• It acts as shock absorbant and lubricant in joints.
• It forms a viscous gel that fills the intercellular spaces. So it resists the invasion

of pathogenic bacteria in tissues.
• It is present in high concentration in embryonic tissues. It is helpful in cell migra-

tion and formation of granulation tissues. It is necessary for wound repair in
embryonic tissues.
• It is found in basement membrane of glomerulus. It is helpful in glomerular
filtration.

6.5.2 A cidic and Sulfated Mucopolysaccharides

Keratan Sulfate
Occurrence

• Keratan sulfate was isolated from the bovine cornea. It is found in the cornea,
cartilage, and bone.

Chemical Composition

• Keratan sulfate is a polymer of disaccharide residues of N-acetyl d-glucosamine
and d-galactose. These residues are linked by beta-(1 → 3) linkages.

• Sulfate residues are present on the C6 of N-acetyl d-glucosamine residues.
• Uronic acid residue in keratin sulfate is absent.

Types of Keratan Sulfate
It is classified into two types on the basis of its occurrence in body tissues:

• Keratan Sulfate-I
It is called corneal keratan sulfate.

118 6 Carbohydrates

• Keratan Sulfate-II
It is also called as non-corneal keratin sulfate. It is found in cartilage and bone.

Functions of Keratan Sulfate

• Corneal keratan sulfate is an important structural constituent of stroma of human
cornea. It is made up of collagen fibers and proteins and glycosaminoglycans. Its
deficiency results into macular corneal dystrophy.

• Non-corneal keratan sulfate is a structural component of cartilages and bone.

Chondroitin Sulfate
Occurrence

• Chondroitin sulfate is found in bone, cartilage, skin, tendons, and heart valves of
humans.

Types and Chemical Composition
Depending on chemical composition, chondroitin sulfate is classified into four
types:

• Chondroitin sulfate A
It is a polymer of disaccharide of N-acetyl d-galactosamine and d-glucuronic
acid. The sulfate residues are present on C4 of N-acetyl d-galactosamine.
It is found in cartilages, cornea, and bones.

• Chondroitin sulfate B
It is a polymer of disaccharide of N-acetyl d-galactosamine and l-iduronic acid.
d-Glucuronic acid undergoes epimerization into l-iduronic acid in chondroitin
sulfate B. The sulfate residues are present on C4 of N-acetyl d-galactosamine.
It is found in human skin, heart valves, blood vessels, lungs, and tendons.
Chondroitin sulfate B is called as “dermatan sulfate” due to its presence in the
skin. It shows weak anticoagulant property and is also called as “beta-heparin.”

• Chondroitin sulfate C
It is a polymer of disaccharide of N-acetyl d-galactosamine and d-glucuronic
acid. The structure of chondroitin sulfate C and chondroitin sulfate A resembles
each other except the position of sulfate residues. The sulfate residues are present
on C6 of N-acetyl d-galactosamine in chondroitin sulfate C.
It is found in tendons and cartilages.

• Chondroitin sulfate D
It is a polymer of disaccharide of N-acetyl d-galactosamine and d-glucuronic
acid. The sulfate residues are present on C6 of N-acetyl d-galactosamine and C2
of d-glucuronic acid.
It is found in shark cartilage.

6.5  Classification of Mucopolysaccharides 119

Functions of Chondroitin Sulfate

• Chondroitin sulfate is the prime structural constituent of ground substance of
bone, cartilage, tendon, and skin.

• It also shows weak anticoagulant property.
• It has a role in neuronal growth and neuronal repair due to its presence in extra-

cellular matrix in brain tissues.
• It maintains elasticity and resilience of articulating cartilage in joints.
• Dermatan sulfate has a role in wound repair in skin and blood vessels. It is impli-

cated in cardiovascular disease, carcinogenesis, and infection.

H eparin
Occurrence

• Heparin was isolated from the liver. It is synthesized by mast cells in the liver.
Heparin also occurs in the blood vessels, lungs, spleen, thymus, and skin.

Chemical Composition

• Heparin is a highly sulfated mucopolysaccharide. It is also called as “alpha
heparin.”

• Its molecular weight varies from 15,000 to 20,000.
• It is a polymer of disaccharide of d-glucosamine and d-glucuronic acid or l-­

iduronic acid. These residues are linked by alpha-(1 → 3) linkages.
• In d-glucosamine, sulfate residues are present at C2 and C6.
• The C2 position in d-glucuronic acid or l-iduronic acid is sulfated.
• In initial stage of heparin polymerization, it contains d-glucuronic acid residues.

Later on, about 95% of d-glucuronic acid is replaced by l-iduronic acid through
epimerization.

Functions of Heparin

• Heparin is stored in granules of mast cells. It is released into blood vessels and
act as anticoagulant.

• Heparin may act as anti-inflammatory in bronchial asthma and ulcerative colitis.
It has been proved in clinical trials.

6.5.3 N eutral Mucopolysaccharides

• Blood group substances are glycoprotein. They consist of neutral mucopolysac-
charides covalently linked to peptides. They contain carbohydrate residues like

120 6 Carbohydrates

N-acetylated galactosamines, N-acetylated glucosamine, fucose, galactose, and
sialic acid.
• Ovalbumin contains neutral mucopolysaccharides linked to peptides.

Rhamnose occurs in nature as deoxy sugar. It is chemically described as
either methyl-pentose or 6-deoxy-hexose. Rhamnose exists as l-rhamnose. It
is an exception to other naturally occurring sugars which exist in d-form.

Fucose occurs as hexose deoxy sugar. It is present in insects and mamma-
lian tissues. It is associated with N-acetylated glycans.

Arabinose is an aldopentose and exists in nature predominantly as l-­
arabinose. It is a component of hemicellulose and pectin. It was initially isolated
from gum arabic or acacia plant whose sap gets hardened on exposure to air.

Hemicellulose is a heteropolysaccharide present in cell walls of plants
along with cellulose. It is made up of glucose, xylose, mannose, galactose,
rhamnose, and arabinose. It has an amorphous structure unlike cellulose
which has crystalline structure.

Mucoprotein is a conjugated protein made up of oligopeptides covalently
linked to glucose, arabinose, xylose, mannose, and fucose carbohydrates.
Carbohydrate proportion of mucoprotein is more than 4%, and it can
range between 10% and 70%. Orosomucoid contains 50% of carbohy-
drates by weight.

Glycoprotein is a conjugated protein made up of oligopeptides covalently
linked to glucose, arabinose, xylose, mannose, and fucose carbohydrates.
Carbohydrate proportion of glycoprotein is less than 4%. It is found in
plasma membrane of cells. Example: Mucin.

Suggested Readings 121

Proteoglycan is a conjugated protein composed of oligopeptides cova-
lently linked to glycosaminoglycan chains. Carbohydrate proportion of pro-
teoglycans is much higher in range between 70% and 90%. Proteoglycans are
negatively charged molecules due to presence of sulfate moieties. They repre-
sent the main constituent of extracellular matrix in connective tissues. They
are of various types depending on the presence of glycosaminoglycans.

Peptidoglycan is also called as “murein.” It is a polymer formed by cross-­
linking of carbohydrates and oligopeptides. It is made up of repeated residues
of N-acetyl glucosamine (NAG) and N-acetylmuramic acid (NAM) covalently
linked to oligopeptides. It forms an important constituent of cell wall of
bacteria.

Suggested Readings

Aspinall GO (1985) The polysaccharides. Academic Press, New York
Bailey RW (1964) Oligosaccharides. Pergamon Press, Oxford
Binkley RW (1988) Modern carbohydrate chemistry. Marcel Dekker, San Diego
Florkin M, Stotz E (1963) Comprehensive biochemistry: carbohydrates. Elsevier, New York
Guthrie RD (1974) Introduction to carbohydrate chemistry, 4th edn. Clarendon Press, Oxford
Heath EC (1971) Complex polysaccharides. Annu Rev Biochem 40:29
Jaques LB (1979) Heparin: an old drug with a new paradigm. Science 206:528–533
Lennarz WJ (ed) (1980) The biochemistry of glycoproteins and proteoglycans. Plenum, New York

Lipids 7

7.1 Definition

Lipids are heterogenous organic compounds which are either fatty acids or
linked to fatty acids and are soluble in organic solvents.

7.2 Classification of Lipids

Lipid classification was proposed by Bloor in 1925. He proposed a term “lip-
ides” to a group of fatty substances.

7.2.1 Simple Lipids

Simple lipids are esters of fatty acids with alcohols. They are also called as
“homolipids.”

Simple lipids can be subdivided into two groups based on type of alcohol.

• Neutral Fats
–– They are esters of fatty acids with glycerol.
–– Three fatty acid molecules are esterified with one molecule of glycerol. So
they are also called as triglycerides or triacylglycerol as in Figs. 7.1 and 7.2.

• Waxes
–– They are esters of fatty acids with monohydroxy aliphatic alcohols. These
alcohols have high molecular weight.
–– True waxes are ester of fatty acids with cetyl alcohol (C16 H33 O) or other
higher long-chain alcohols.

© Springer Nature Singapore Pte Ltd. 2019 123
A. Gupta, Comprehensive Biochemistry for Dentistry,
https://doi.org/10.1007/978-981-13-1035-5_7

124 7 Lipids
Fig. 7.1 Glycerol
1 CH2OH
2 CHOH
3 CH2OH
[Glycerol]

Fig. 7.2 Triglyceride O

(∝) 1 CH2 – O – C – R1
O

(β) 2 CH – O – C – R2
O

(∝′) 3 CH2 – O – C – R3

[Triglyceride]

Examples:
1. “Beeswax” is an ester of palmitic acid with triacontanol (C30 H62O). It is

also called myricyl alcohol. It is an animal wax.
2. “Spermaceti” is found in the head of sperm whale. It is a wax and is pro-

duced inside spermaceti organ in sperm whale. Spermaceti is also found in
oils of whales. It is an animal wax.
3. “Lanolin” is also called as “wool wax.” It is obtained from sebaceous
glands of sheep.
4. “Cerumen” is also called as “earwax.” It is secreted by ceruminous glands
in external auditory canal in humans.
5. “Carnauba wax” is obtained from palm leaves. It is a diester of
4-­hydroxycinnamic acid and ω-hydroxycarboxylic acids with long-chain
alcohols. It is a plant wax.
6. “Paraffin wax” is a synthetic wax obtained as petroleum product. It is made
up of long chain of alkane hydrocarbons.
–– Cholesterol ester is an ester of fatty acids with cholesterol.
–– Vitamin A ester is an ester of palmitic acids with retinol.
–– Vitamin D ester is an ester of palmitic acid with cholecalciferol.

7.2.2 Compound Lipids

Compound lipids are esters of fatty acids and alcohols containing additional groups.
They are also called as “heterolipids.”

Compound lipids can be subdivided based on presence of additional group as
follows:

• Phospholipids
Phospholipids are composed of fatty acids, alcohol, phosphoric acid, and nitrog-
enous base.