Course: Bioinformatics

Course Code: CHT2007

Unit- I Introduction to Biomolecules

By
Dr. Meenal V. Joshi
RCOEM, Nagpur
Unit- I Introduction to Biomolecules

Carbohydrates: Introduction and classification

Amino Acid: Chemistry properties and metabolism.
Proteins: primary, Secondary, tertiary and quaternary structure,
Lipids: Chemistry, Metabolism of fatty acids, Phospholipids,
Cholesterol regulation of metabolism.
Nucleic Acid: Chemistry of DNA and RNA,
Vitamins: Structure and functions of some vitamins.
Carbohydrates
Introduction: Carbohydrates constitute one of the most
important groups of natural products.
Earlier, carbohydrates were defined as compounds
containing carbon, hydrogen and oxygen, the latter two
elements being present in the same ratio as in water

i.e. they were regarded as the hydrates of carbon

(carbo--carbon; hyarates-hydrates)
and thus corresponded to the formula CX(H2O)y,

e.g. Glucose C6H1206

Cane-sugar C12H22O1l etc.
But later on it was found that certain carbohydrates do
not correspond to this formula
e.g. rhamnose, C6H12O5; rhamnohexose C7H14O6,
digitoxose C6H12O4
while several compounds although not carbohydrates,
correspond to this formula
e.g. formaldehyde. CH2O, acetic acid C2H4O2,
lactic acid C3H6O3, inositol C6H12O6, etc,

So now-a-days carbohydrates are defined as the

optically active polyhydroxyaldehydes or ketones or
substances that can be hydrolysed to either of them.
Importance of Carbohydrates

1. Source of energy: They serve as source of energy

(e.g. sugars) and also as store of energy (e.g. starch and
glycogen).
2. Support the plant tissues (e.g. cellulose)
3. Form the major constituent of the shells of crabs and
lobsters.(e.g. Chitin)
Other important contributions of carbohydrates:

Sugars make fruits sweet and yield alcohol on fermentation;

cellulosic materials such as cotton, linen, jute, straw, grass, wood,
etc. supply clothes, paper, fuel, piastic, lacquers, paints explosives.
 Ribose and deoxyribose (aldopentoses) are components of
nucleic acids (RNA-ribonuclelc acid, and DNA-deoxyribonucleic
acid) which determine human heredity.

It must be noted that the ultimate source of all carbohydrates is

plants which built them, from carbon dioxide and water by
photosynthesis.
Nomenclature:
The nomenclature of the sugars is complex in the respect
that specific names are required to designate each
compound. However, the suffix -ose is employed for
naming sugars. The portion of the name preceeding this,
however. sometimes reflects the origin and history of the
compound,
e.g. the name lactose
(milk sugar) is derived from latin word lactis means milk.
 Classification of Carbohydrates

Sugars Non-Sugars
(Polysaccharide)

Monosachharides Oligosachharides

Aldose Ketose
Carbohydrates may be classified into two broad groups: sugars and
non-sugars (polysaccharides).
1.Sugars: Sugars are sweet, crystalline substances, and soluble in
water. Their molecular weights are known and fixed for a particular
compound. They are subdivided into two groups.

(i)Monosaccharides and (ii) Oligosaccharides

(ii)Monosaccharides: The monosaccharides are

polyhydroxyaldehydes or ketones which cannot be hydrolysed to
simpler sugars.

They may again be classified according to the nature of carbonyl

group ; those with an aldehyde group are known as aldoses, and
those with a keto group as ketoses.
Aldoses and ketoses are further divided on the basis of the number
of carbon atoms in the molecule.

A. Nature of carbonyl : Aldoses-having aldehydic group.

Ketoses-having ketonic group.

B. Number of carbon atoms :

Trioses having 3-C
Tetroses having 4-C
Pentoses having 5-C
Hexoses having 6-C
Heptoses having 7-C etc.
(ii) Oligosaccharides: These yield two to ten monosaccharide
molecules on hydrolysis, and are again classified into various
groups depending upon the number of monosaccharide units
form on hydrolysis.

(A) Disaccharides: The disaccharides are sugars which on

hydrolysis give two moles of the same or different
monosacchrides, e.g. sucrose yields one mole each of glucose
(an aldohexose) and fructose (a ketohexose) on hydrolysis.
 Hydrolysis of Maltose

Hydrolysis of Sucrose
(B) Trisaccharides : These give three moles of monosaccharides on
hydrolysis, e.g. raffinose

Hydrolysis of raffinose
(C) Tetrasaccharides : These give four moles of monosaccharides on
hydrolysis, e.g. stachyose C21H42O21
2. Non-sugars or Polysaccharides :They are usually tasteless,
amorphous solids and either insoluble in water or form
colloidal suspension. Polysaccharides have the properties
typical of high polymers, e.g. the molecular weight of a
polysaccharide varies considerably. Although they are tasteless
on hydrolysis with dilute acids they yield many sweet
monosaccharide molecules. The common and widely
distributed polysaccharides correspond to the general formula
(C6H10O5)n e.g. starch, cellulose, etc.
Only group of polysaccharides which are not so widely distributed
in nature is the pentosans, (C5H8O4)n

Thus chemically, polysaccharides are long chains or polymers of

monosaccharides. The important monosaccharides found in
polysaccharides are glucose, xylose and arabinose. The
polysaccharide may be made up of a single type or different types
of monosaccharide units; the two corresponding polysaccharides
are respectively known as homopolysaccharides and
heteropolysaccharides. Starch, cellulose and lnulin
are examples of homopolysaccharides, while chondroitin sulphate
is the common example of heteropolysaccbarides.
Homopolysaccharides

Structure of Starch
Heteropolysaccbarides.

Structure of Chondroitin sulphate

 From the classification of carbohydrates we find that
monosaccharides are simplest and ultimate carbohudrates and
all others are considered as the condensation products of
monosaccharides. Among the monosaccharides pentose and
hexose sugars are more important and hexose is most important
from standpoint of occurrence hence this group is studied in
detail to illustrate the principles of carbohydrate chemistry.
METABOLISM OF CARBOHYDRATES

Carbohydrates represent one of the major sources of energy for the

animal kingdom. Over one-half of the food in the normal diet of a
human consists of carbohydrates; usually in the form of starches.
human being, digestion of starch starts in the mouth where It
(starch) is mixed with salivary amylase. The salivary amylase
breaks down the starch into smaller dextrin units. In the stomach,
very little carbohydrate digestion takes place because the Simple
acid-catalyzed hydrolysis of the acetyl linkages is too slow at body
temperatures. Thus the carbohydrates mainly undergo digestion in
the small intestine where they are attacked by pancreatic amylase
and other enzymes secreted by the mucosal cells of the Intestine.
In the small intestine, the various carbohydrates are converted
to galactose, fructose, and glucose Which are transported to the
liver through the portal vein. In the liver, galactose and fructose
are converted to glucose by the appropriate isomerases.
Glucose is then either converted to liver glycogen and stored
there until It is required to maintain the appropriate blood
sugar level, or It is directly passed into the Circulatory system
and transported to the cells.
It is only the glucose sugar that circulates in the blood and is,
thus, commonly known as blood sugar. The normal
concentration of glucose in the blood is 70 to 100 mg/100mL
of blood. The abnormally low and high concentration of
glucose in the blood to the above mentioned values are known
as hypoglycemia and hyperglycemia resp.
The concentration of glucose in the blood is mainly controlled
by synthesis and degradation of glycogen.
The blood glucose-glycogen balance is chiefly controlled
by three hormones
1.Adrenaline: Stimulates the breakdown of glycogen
(glycogenolysis)
2.Glucagon: Promotes breakdown of liver glycogen
3.Insulin: Key factor in glycogen synthesis.
 Diagram: METABOLISM OF CARBOHYDRATES

Carbohydrates + Salivary amylase

Mouth break down
Small Dextrin units
Stomach acid-catalyzed hydrolysis

Dextrin
pancreatic amylase
Small intestine
Galactose + Fructose + Glucose

Isomerases
Glucose

Converted to liver glycogen Directly passed into the Circulatory

and stored in liver system and transported to the cells
Among the various carbohydrates that are synthesized within the
organism or absorbed from the diet, glucose is quantitatively the
most important that is available to the body for various purpose.
Therefore the discussion of metabolism of carbohydrates is
metabolism of glucose.
The general metabolism of glucose may be studied under two
headings
1.The sources of glucose to the organism
2.Utilization of glucose by organism
 1. Sources of Glucose to organism

Exogenous source Endogenous source

Ex: Dietary carbohydrates Ex: Liver glycogen,
Muscle glycogen
1. Exogenous sources:
The direct exogenous source of carbohydrates is Dietary
carbohydrates which become available to various tissues by
the process of digestion. The digestible polysaccharides and
disaccharides are hydrolysed in the intestinal lumen and
Within the epithelial cells respectively to their
monosaccharide constituents,
VIZ, starch, glycogen, and maltose to glucose;
lactose to glucose and galactose;
sucrose to glucose and fructose,

In addition to the above common sugars, small amounts of

pentoses and mannose are also present in the foodstuff.
Although all monosaccharides are practically completely
absorbed (almost entirely in the small intestine), the rates of
absorption of the various monosaccharides are different and
coincide with the following order

Galactose> Glucose> Fructose > Mannose > Xylose >Arabinose

At least two mechanisms are involved during absorption, viz,

(i)simple diffusion which is dependent on the sugar
concentration gradient between the intestinal lumen, mucosal
cells, and plasma and
(ii)A transport system which is independent of concentration
gradient.
 After absorption into the portal blood, carbohydrates before
entering the systematic circulation pass to the liver where
the galactose and fructose are converted to glucose, the most
important monosaccharide,
 As far as pentose sugars (xylose, arabinose and ribose)
present in the diet are concerned, their fate after absorption
is obscure.
1. Endogenous sources:

The major endogenous -glucose source is the liver

glycogen followed by muscle glycogen,
The Liver glycogen is hydrolysed to glucose on demand
(glycogenolysis);
The muscle glycogen is not directly convertible to blood
glucose, it is converted into glucose via lactate formed in
the muscles
In addition to glycogen small quantities of endogenous
galactose, mannose, and possibly pentoses are converted
to glucose under certain circumstances.
 Non carbohydrate sources

Amino acids Glycerol Lactate

(from Protein) (from fats) (from anaerobic
oxidation of glucose)

Synthesis of Glucose in the body (Liver)

Amino acid which is a carbohydrate precursors are known as

glucogenic, and the process of glucose synthesis from such
compound is known as glucogenesis.
 2. Utilization of Glucose
When the glucose molecule is introduced or synthesized in the
body it can undergo several metabolic pathways such as storage,
oxidation, synthesis of fat, conversion of other carbohydrates,
conversion to amino acids, etc.

(i)Storage of glucose as glycogen (glycogeneis) : In case the

body does not feel the urgent physiological demands for glucose,
excess of it may be deposited as glycogen (glycogenesis) in the
various tissues, especially liver. Since the excess of glucose that
can be stored in the body is limited, still excess of glucose is
converted to fatty acids and stored as triglycerides in the fat
depots.
Storage of carbohydrates, glycogen synthesis and breakdown:

In the absence of the urgent physiological demand for oxidative

energy or conversion to special products, excess of glucose is
stored in the form of glycogen in the liver or other tissues.
The process of biosynthesis of glycogen from glucose (or other
sugar) is known as glycogenesis.
glycoge is synthesized practically in all tissues of the body but
the major sites are liver and muscles.
The storage of glucose in the form of glycogen, which is
converted back to glucose, at the time of requirement, is very
important because in the absence of this process the tissues
would be flooded with excess of glucose immediately after meal
and starved of it at all other times.
Why glucose is stored in the polymer form (in the form of
Glycogen polymer)?

The carbohydrate reserve in the-adult human liver (1·8 kg) is

about 190 gm and since accumulation of such a large amount of
the smaller molecule like glucose will give concentration of
glucose inside liver cells of the order of 0·3 M, the osmotic
pressure inside the liver cells will nearly be doubled lead to
disastrous results. It is, therefore, advantageous to the organism
to store its glucose in the form of polymer glycogen. Which has
a high molocular weight and correspondingly low osmotic
pressure.
How excess glycogen is stored?
In case carbohydrate rich diet is taken, the liver tissue may
immediately store glycogen about 5-6% of its weight. The liver
glycogen may be exhausted after a fast of 12-18 hours. Other
important store of glycogen is muscles which may contain about
0·7 - 1·0% glycogen and since an adult human has about 35Kg
muscles, as much as 245-350 gm of glycogen may be stored in
muscles. Muscle glycogen is utilized in case of severe body
exercise or when the liver glycogen is completely exhausted.
Now since the of glycogen which can be stored in the body is
limited, excess quantities of glucose are converted to fatty acids
and stored as triglycerides (fat).
Physiological significance of liver glycogen

1. Glycogen is the only immediately available reserve of

blood glucose.
2. When liver glycogen is high, the rate of deamination
of amino acids in the liver is depressed and the amino
acids remain available for protein synthesis.
3. A high level of liver glycogen depresses the rate of
ketone formation from long chain fatty acids.
4. Detoxication by acetylation or glucuronide formation
of many substances is favored by a high liver
glycogen content.
5. Glycogen rich liver is protected against the harmful
effects of many poisons, e.g. carbon tetrachloride,
ethanol, arsenic and bacterial toxins.
A glucuronide, also known as glucuronoside, is any substance
produced by linking glucuronic acid to another substance via
a glycosidic bond.

The glucuronides belong to the glycosides.

Glucuronidation, the conversion of chemical compounds to

glucuronides, is a method that animals use to assist in the
excretion of toxic substances, drugs or other substances that
cannot be used as an energy source.
Glucuronic acid is attached via a glycosidic bond to the
substance, and the resulting glucuronide, which has a much
higher water solubility than the original substance, is eventually
excreted by the kidneys.

Enzymes that cleave the glycosidic bond of a glucuronide are

called glucuronidases.
Glycogenesis (Glycogen Synthesis)

Synthesis of Glycogen from glucose can occur in most of the

tissues of body; Liver and muscles are the most important site
Liver is the only viscera which can synthesize glycogen from
monosaccharides other than glucose.
Polymerization of glucose to glycogen in liver and muscles are
found to be similar.

Various steps involved in glycogenesis are:

1.Phosphorylation of glucose
2.Conversion of glucose-6-phosphate to glucose-1-phosphate
3.Conversion of glucose-1-phosphate to UDPG
4.Conversion of UDPG to glycogen
5.Branching of Glycogen
 Structure of Glycogen

A core protein is surrounded by

branches of glucose units. The
entire globular complex may
contain approximately 30,000
glucose units
Image : Schematic two-dimensional
cross-sectional view of glycogen
1. Phosphorylation of glucose: Glucose is phosphorylated
(activated) by ATP in the presence of enzyme hexokinase or
more specifically glucokinase and Mg2+ (activator) to
glucose-6-phosphate. Both of theses enzymes are found in
higher mammals
Glucokinase or
Glucose + ATP Glucose-6-phosphate + ADP
Hexokinase, Mg 2+

The enzyme glucokinase (hexokinase) is inhibited by

adrenalcortical hormones (glucocorticoids) and is this inhibition is
facilitated by anterior pitutary hormones. However inhibition is
removed by insulin.
 Formation of glucose-6-phosphate acts as a locking mechanism
to keep the glucose within the cell since it is non permeable to cell
membrane while glucose is readily permeable.
2. Conversion of glucose-6-phosphate to glucose-1-phosphate:
Glucose -6-phosphate is reversibly transferred to glucose-1-
phosphate in reaction catalysed by the enzyme
phosphoglucomutase. The enzyme itself is phosphorylated, and
the phospho group takes part in a reversible reaction in which
glucose 1,6-diphosphate is formed as an intermediate.

Enz-P + Glucose-6-phosphate Enz+ Glucose 1,6-diphosphate

Enz+ Glucose-1-phosphate
 3. Conversion of glucose-1-phosphate to UDPG

The glucose-1-phosphate now combines with uridine

triphosphate (UTP) in the presence of uridine diphosphate
glucose pyrophosphorylase (UDPG pyrophosphorylase) to form
the active nucleotide uridine diphosphoglucose (UDPG) with the
elimination of inorganic pyrophosphate (P-P).

UDPG-
Glucose 1-P +UTP Pyrophosphorylase
UDPG + Pyrophosphate (P-P)
(converted into H3PO4)
 4. Conversion of UDPG to glycogen
Under the influence of the enzyme glycogen synthetase
(glycogen transferase), the C1 of the activated glucose of
UDPG forms a glycosidic bond with the C4 of the terminal
glucose residue of glycogen, liberating uridine diphosphate
(UDP). The UDP formed as a byproduct is converted to UTP in
the presence of ATP.

Glycogen
UDPG + Glycogen Primer (C6)n (C6)n+1 + UDP
Synthetase
Phosphokinase
UDP +ATP UDPG +ADP

Remember that one glucose unit is added to glycogen primer

via1,4-linkage at one time. By the successive 1,4-linkages by
glucose units to the preexising glycogen chain, the branches of
glycogen tree becomes elongated
Glycogen synthetase: is found to exist in two forms
synthetase-D (dependent) which is active only in presence of
glucose-6-phosphate and synthatase-I (independent) which is
independent of the concentration of glucose-6-phosphate and
is the active enzyme for all practical purposes. Insulin favours
the conversion of synthetase-D to synthetase-I and hence
accelerates glycogen synthesis while epinphrine and glucagon
favours the conversion of synthetase-I to synthetase-D, by
their stimulating action on the production of cyclic AMP and
hence inhibit glycogen synthesis.
5. Branching of Glycogen:
When the chain has been lengthened to a minimum of 11 glucose
residues, a second enzyme, amylo-1,4 1,6-transglucosidase,
commonly known as branching enzyme, catalyzes transfer of a
terminal oligosaccharide fragment of 6 or 7 glucosyl residues
from the end of the main glycogen chain to the 6-hydroxyl
group of a glucose residue of the same or of another glycogen
chain, in the such manner as to form an alpha 1,6 linkage and
thus establishes a new branch point in the molecule.
The existing branches of the glycogen molecule are extended
by the addition of new glucose molecules from UDPG under
the influence of glycogen synthetase. Thus under the combined
action of glycogen synthetase and branching enzyme, the
glycogen molecule grows like a tree. The molecular weight of
glycogen thus synthesized may vary from 1 to 4 millions or
more.
Inborn Error of glycogen anabolism:
A form of glycogen storage deficiency resulting from inherited
lack of glycogen synthetase has been described. Such
individuals are not being able to form proper amount of
glycogen, this inborn error of metabolism is characterized by
fasting hypoglycemia (less than normal blood glucose levels)
with convulsions and mental retardation.
Normal individuals store approximately 100 gm of glycogen
in liver and about 250g in muscle.
Glycogenesis: Glycogen-Synthesis

Glycogen – Homopolysaccharide of Glucose

Glycogen is stored in liver and muscle
Glycogen is also called as Animal Starch
Glycogenolysis:
The process of breakdown of glycogen to glucose (as in liver
and kidney) or glucose-6-phosphate (as in muscles) is known as
glycogenolysis.

The process involves the following steps

1. Cleavage of α-1,4 linkages

2. Transfer of a trisaccharide unit from one branch to the other
3. Cleavage of α-1,6 linkages
4. Conversion of glucose-1-phosphate to glucose-6-phosphate
5. Hydrolysis of glucose-6-phosphate to glucose
1. Cleavage of α-1,4 linkages:
catalysed by the enzyme
inorganic phosphate. The
phosphorolysis, splits up the
phosphate.
The breakdown of glycogen is
phosphorylase in presence of
reaction, being known as
terminal glucose as glucose-1-

(C6)n + Pi (C6)n-1 + Glucose-1-phosphate

 In this way a glycogen chain can be shortened by one

glucose unit at a time.
 It is important to note that the enzyme phosphorylase
attacks only on α-1,4 linkages in glycogen.
 It can neither attack on α-1,6 linkages at the branching
points nor can by-pass them to attack next α-1,4 linkages.
 The removal of α-1,4 glucosyl residues from the outermost
chains of the glycogen molecule continues until about 4
glucose residues remain on either side of a α-1,6 branch.

2. Transfer of trisaccharide unit from one branch to the

other: The enzyme α-1,4 - α-1,6- glucan transferase
transfers a trisaccharide unit from one branch to the
other, exposing the α-1,6 branch points

3. Cleavage of α-1,6 linkages: The α-1,6- linkages are

cleaved by another enzyme known as debranching
enzyme (α-1,6- glucosidase) which removes the glucose
unit linked by α-1,6- linkages to free glucose and thus
allows the phosphorylase to continue its attack on the
chain. Thus a glycogen molecule can be completely
broken down by the combined action of phosphorylase,
transferase and debranching enzymes.
4. Conversion of Glucose-1-phosphate to glucose-6-
phosphate: Glucose-1-phosphate obtained under the
influence of phosphorylase is isomerised to glucose-6-
phosphate by action of phosphoglucomutase.

5. Hydrolysis of glucose-6-phosphate to glucose: The

glucose-6-phosphate is then hydrolysed under the
influence of glucose-6-phosphatase (present only in liver
& kidney) to free glucose which can diffuse from the cell
into the extracellular spaces including blood. Thus
glycogen is hydrolysed finally to free glucose in liver and
kidney and to glucose-6-phosphate in muscles.
 Glycolysis: Glycolysis is the major pathway for utlization
of glucose & is found in all cells.
It consists in the degradation of glycogen, glucose or other
sugars to pyruvate and/or lactate.
It is a unique pathway of glucose degradation since it can
utilize oxygen if available (aerobic) or it can function in the
absence of oxygen (anaerobic).
 All the enzymes of the glycolysis pathway are found in
extra mitochondrial soluble fraction of cell , the cytosol.
The process of glycolysis is important owing to the
following three points.
i. It is obligatory to one of the ways of carbohydrate oxidation,
since the pyruvate or lactate formed by glycolysis is then
oxidised to CO2 & H2O.
ii. Intermediates formed in the glycolytic reactions also lead to
the synthesis of fat from carbohydrates
iii. Glycolysis itself also yield some energy in the form of ATP
which can be utilized for muscle contraction and other
functions. This is especially important when energy in excess
of that which can be provided by oxidative processes is
required such as during sudden strenous exercise.
Structure of Glucose

Structure of Glucose
What does insulin do?
Insulin moves glucose from your blood into cells all over your body. Glucose
comes from both food and your body’s own natural release of stored glucose.
Think of insulin as the “key” that opens the “doors” of the cells in your body.
Once insulin opens your cell doors, glucose can leave your bloodstream and
move into your cells where you use it for energy. Without enough insulin,
glucose can’t get into your cells and instead builds up in your blood
(hyperglycemia).

Why galactose is absorbed easily than glucose:

SGLT1 has a higher affinity for galactose than GLUT2 has for
glucose. This means that when galactose is present, it is more
efficiently taken up into the cells lining the small intestine for
absorption into the bloodstream.