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BIOMEDICAL IMPORTANCE OF

CARBOHYDRATE

INTRODUCTION

The function of carbohydrates are


major

source of energy for man, e.g. glucose.


serve as reserve food material, e.g. glycogen
components of several structure : components of skin,
connective tissue, tendons, cartilage and bone.
components of cell membrane and nervous tissue.
components of nucleic acids and blood group
substances.
involved in cell-cell interaction.

IMPORTANT MONOSACCHARIDES
1.

PENTOSES
Ribose:
Found in nucleic acids
Forms structural elements of nucleic acid and coenzymes
Intermediates of pentose phosphate pathway ATP, NAD,
NADP, flavoproteins etc

2.

HEXOSES
Glucose:
most important carbohydrate
can be converted into glycogen, ribose, and galactose

GLUCOSE

Glucose

is major fuel for all types of cells in body.


Its oxidation producesenergy.
Glucose consumption per day varies from one organ to another.
Some organs like brain prefers glucose as fuel than fat and
protein.
Brain consumes about 100 gm of glucose per day.
Rate of glucose oxidation is more in cancer cells.
Glucose is used for the formation of glycogen, pentoses, lactose
and mucopolysaccharides.
Since brain is totally dependent on glucose for its energy needs

GLUCOSE
Deficiency or absence of enzymes of glycogen metabolism
causes glycogen storage diseases.
In erythrocytes, 2, 3-BPG is formed from glucose. 2, 3-BPG
facilitates the release of oxygen from oxyhemoglobin.

Dietary galactose and fructose are converted to glucose.


Deficiency of enzymes of galactose and fructose
metabolism causes galactosemia and fructosemia,
respectively.

Most common metabolic disease diabetes mellitus is due to


defective glucose metabolism.

GLYCOLYSIS

Degradation of glucose to two molecules of pyruvate or


lactate
If glucose is degraded to pyruvate then it is called as
aerobic glycolysis. Usually it occurs in presence of oxygen.
If glucose is degraded to lactate then it is anaerobic
glycolysis. Usually it occurs in the absence of oxygen.
Enzymes of glycolysis are present in the cytosol of most of
the cells present in the body.

GLYCOLYSIS

Dietary glucose enter liver through portal venous system


after its absorption from the intestine.
Liver distributes glucose to all other organs (cells) of body.
Entry of Glucose in to Cells
1. Liver:

Glucose enters liver cells by facilitated diffusion.


It is an insulin-independent transport mechanism

2. Extra hepatic tissues

Glucose enters adipocytes, erythrocytes, brain and skeletal


muscle by insulin-dependent facilitated transport.

Medical and Biological Importance of Glycolysis


1.

2.

3.

4.

5.

Glycolysis provides energy to cells. Anaerobic glycolysis meets rapidly


energy for skeletal muscle contraction
Heart is mainly aerobic organ, so myocardial ischemia decreases
glycolytic ability of cardiac muscle.
Erythrocytes gets energy from glycolysis, so deficiency pyruvate kinase
causes haemolytic anemia.

Deficiency of muscle phosphofructo kinase causes decreased muscular


performance and fatigue.
Dietary fructose & galactose are also metabolized by glycolisis.

Medical and Biological Importance of Glycolysis


6.

Glycolysis provides precursors for formation of lipids and


amino acids

7.

Glycolytic intermediates pyruvate and glyceraldehydes-3phosphate are

8.

9.

e.g. pyruvate is converted to alanine serves as precursor for


triglyceride formation

used for synthesis of cholesterol, thiamine and pyridoxine in


tuberculosis, malaria and gastritis causing organisms.

Glycolysis is the major energy source for rapidly growing


malerial parasite in R.B.C.
In brain tumors lactate production is 10 times more.

GLYCOGENESIS

Glycogenesis

Is Synthesis of Glycogen from Glucose


chiefly occurs in liver and skeletal muscle.
Excess glucose is stored as glycogen under fed conditions.
In muscle, + 245 gms of glycogen & in liver + 72 gms of
glycogen is stored under well fed condition.

Skeletal muscle prefers to store energy as glycogen because


1. Fat can not be oxidized under anaerobic condition.
2. Acetyl-CoA of fat oxidation can not be converted to glucose.
3. Skeletal muscle is unable to mobilize fat rapidly.

GLYCOGENOLYSIS

Glycogenolisis
converts

glycogen to glucose and other small molecules.


occurs in liver and muscle.
The

end product of glycogenolisis :

In

liver: glucose
In skeletal muscle: glucose-6-phosphate or lactate

Lysosomes degrades + 1-3% of cellular glycogen.

Medical Importance Of
Glycogenolisis
1.

2.

3.

In liver, glycogenolysis contributes glucose to


maintain blood glucose level in between meals.
In muscle, glycogenolysis meets its energy in
between meals.
Inhibition of glycogen phosphorylase decreases
glycogenolysis which leads to low blood glucose
level.

PENTOSE PHOSPHATE PATHWAY


1.

2.

3.

4.

also called as hexose monophosphate shunt (HMP Shunt),


phosphogluconate oxidative pathway and direct oxidative
pathway (directly oxidizes glucose to CO2)
In this pathway, oxidation of glucose generates NADPH reducing
power. NADPH serves as hydrogen donor in reductive biosynthesis.
This pathway are present in cytosol of liver, adipose tissue,
erythrocytes, neutrophils, adrenal cortex, thyroid, testis, ovaries
and lactating mammary gland.

In the skeletal muscle the pathway is less active.

Biological Importance of HMP Shunt


1.

NADPH is used for biosynthesis of several important


compounds
(a) In liver, used for fatty acid synthesis, cholesterol synthesis, bile acid
synthesis, glutamate synthesis and cytochrome P450-hydroxylase
system.
(b) In adrenal cortex and gonads, used for cholesterol and hormone
synthesis.
(c) In the adipose tissue, used for fatty acid synthesis.
(d) NADPH is used for formation of deoxy ribonucleotides and
pyrimidine nucleotides.

Biological Importance of HMP Shunt


2.

In RBC, NADPH is used for

Formation of reduced glutathione from oxidized glutathione.

Reduced glutathione is required for the removal of H2O2 by


glutathione peroxidase (Fig. 9.11)

for the conversion of methaemoglobin to normal hemoglobin and


for maintenance of SH groups of erythrocyte proteins.
So, reduced glutathione is essential for integrity of normal red cell
structure.

Usually cells with reduced glutathione level are more prone to


hemolysis.

Fig. 11.1 (a) Schematic diagram showing production of reduced coenzymes on oxidation of
substrate with subsequent oxidation of them by O2 and formation of ATP

Fig. 11.1 (b) Transfer of electrons from substrate to O2 in coupled oxidation-reduction


reactions

(a) In respiratory chain, O2 is used as tinal electron acceptor and reduced to water.
(b) Apart form respiratory chain, several enzymes use O2 as final electron acceptor
andproduce H20 2.
(c) Several new compounds are synthesized by directly incorporating O2 into certain
substances.
(d) Respiratory O2 is also required for the removal of toxins and drugs from the body.
(e) Superoxide ion derived from 02 function as microbicide.

Biological Importance of HMP Shunt


3.

4.

5.

In neutrophils, NADPH is required for the formation of


superoxide by NADPH oxidase.
Pentoses produced in this pathway are used for nucleic
acid synthesis and nucleotide coenzymes like NAD+,
FAD and FMN synthesis.
Non-oxidative phase of the pathway converts
pentoses of endogenous or dietary nucleic acids into
intermediates of glycolysis where they are, further
oxidized togenerate energy.

Biological Importance of HMP Shunt


6.Inter conversion of three, four, five, six and seven carbon
sugars in the non-oxidative phase metabolically connects
these sugars to glycolysis.
7. HMP shunt converts xylulose of uronic acid pathway to
either glucose or intermediates of glycolysis.
8. This pathways converts glucose to CO2 directly and hence
CO2 is the end product ofthe pathway.
9. In plants, a modified form of this pathway is responsible for
the synthesis of glucose from CO2.

Uronic Acid Pathway

In this pathway, glucose is oxidized to uronic acid.


No energy is produced
Since free uronic acid can not be used for proteoglycan and other
conjugation reactions it is produced as active uronic acid or UDPglucuronic acid from UDP-Glucose.
UDP-glucuronic acid serves donor of glucuronic acid.
Furhter this pathway converts free or unused glucuronicacid to Dxylulose-5-phosphate which is converted to intermediates of
glycolysis by non oxidative phase of HMP shunt.

Medical and Biological Importance of


Uronic Acid Pathway
1.

2.

3.

4.

produces glucuronic acid, ascorbic acid and pentoses from glucose.


Glucuronic acid is used for synthesis of proteoglycan for
conjugation with bilirubin,steroid hormones and for detoxification
of drugs.

Glucuronic acid formed from degradation of endogenous


proteoglycans by action of lysosomal enzymes and dietary
glucuronic acid are utilized for energy production by this pathway
via HMP shunt after conversion to xylulose.
In plants and mammals other than man Vit C is synthesized in this
pathway from L-gulonate.

POLYOL PATHWAY

1.

2.
3.

converts glucose to fructose.


Other names of this pathway are sorbitol pathway and alditol
pathway.
Medical and Biological Importance
Fructose is synthesized in seminal vesicle where it serves as fuel for
spermatozoa.
Placenta also produces fructose. It is source of energy for foetus.
In diabetics, excess glucose that enters lens is converted to sorbitol.
Lens is impermeableto sorbitol, so it accumulates in the lens and
cause swelling of lens. This may be ultimately responsible for
cataract formation.

Need for Glucose Synthesis

Synthesis of glucose from non-carbohydrates is more important because supply of


glucose to tissues whose only fuel is glucose must be maintained under the conditions
of glucose shortage.
Apart from non-carbohydrates glucose is formed from other hexoses like galactose
and fructose.
Synthesis of glucose from galactose and fructose occurs in fed conditions.

Gluconeogenesis (Neoglucogenesis)

converts non-carbohydrate substance to glucose.


Glucose is synthesized from pyruvate, which is derived from glucogenic amino acids,
intermediates of TCA cycle and glycerol.
Since pyruvate can be formed from lactate by the reversal of lactate dehydrogenase
reaction synthesis of glucose occurs from lactate also.
Gluconeogenesis is an energy-consuming process.

Site Gluconeogenesis occurs mainly in the liver and kidney. Enzymes of


gluconeogenesis are present in mitochondria and cytosol.

Medical and Biological Importance of


Gluconeogenesis
1.

2.

3.

4.

5.
6.

Meets glucose requirement of body when carbohydrate is in short supply


i.e., during fasting and starvation.
Tissues like brain, skeletal muscle, erythrocytes and testis are completely
depend on glucose for energy. Body glycogen can meet glucose
requirement for only 24 hours.

Gluconeogenesis clears metabolic products of other tissues from blood.


For example, lactate produced by erythrocytes, skeletal muscle, glycerol
produced by breakdown of adipose tissue triglycerides and amino acids
produced by muscle protein breakdown.
Gluconeogenesis converts excess of dietary glucogenic amino acids into
glucose.
Lactic acidosis occurs in fructose-1, 6-bis phosphatase deficiency.
Gluconeogenesis is impaired in alcoholics.

IMPORTANT OTHER MONOACCHARIDES

Fructose
Main

nutritional source of energy for spermatozoa and


is found in seminal fluid
Can be converted to glucose in live

Galactose
found

as a component of lactose in milk


Synthesized in the lactating mammary gland
Constituent of glycolipids and glycoproteins
Can be converted to glucose in the liver

IMPORTANT DISACCHARIDES

1.

Most common disaccharides are maltose, lactose and sucrose


Maltose

2.

contains two glucose units


is a reducing sugar because anomeric carbon of second
glucose is free.
formed during the hydrolysis of starch.

Lactose

contains one glucose and one galactose.


is a reducing sugar
is synthesized in mammary gland and hence it occurs in milk

IMPORTANT DISACCHARIDES
3.

Sucrose

contains glucose and fructose


is a non reducing sugar

4. Isomaltose
contains

two glucose units


is disaccharide unit present in glycogen, amylopectin
and dextran.

Glycogen

Glycogen
is

the major storage polysaccharide (carbohydrate) in


human body.
is mainly present in liver and muscle.

HETEROPOLYSACCHARIDES

Heteropolysaccharides
also called as mucopolysaccharides and glycosaminoglycans.
Mucopolysaccharides
consist of repeating disaccharide units
component of connective tissue (as structural
polysaccharides) and mucous secretions.
combines with collagen and elastin and forms extracellular
medium or ground substance of connective tissue.
components of extracellular matrix of bone, cartilage and
tendons.
also function as lubricants and shock absorbers.

Important mucopolysaccharides or
glycosaminoglycans

Hyaluronic Acid (HA)


is

present in synovial fluid and function as lubricant.


is also present in skin, loose connective tissue, umbilical
cord and ovum.
is present in vitreous body of eye.

Chondroitin sulfate

Chondroitin sulfates
are

components of cartilage, bone and tendons.


are also present in the cornea and retina of the eye.
content decreases in cartilage as age advances.

Heparin

Heparin
is

a normal anti-coagulant present blood.


is produced by mast cells present in the arteries, liver,
lung and skin.
Unlike other glycosaminoglycans, heparin is an
intracellular component.

Dermatan Sulphate
is

present in skin, cornea and bone.


has a role in corneal transparency maintenance.

Keratan Sulphates
are

components of cartilage, cornea and loose


connective tissue.
is important for corneal transparency.

GLYCOPROTEINS

Glycoproteins
are found in mucous fluids, tissues, blood and in cell
membrane
are proteins containing short chains of carbohydrates that
are usually oligosaccharides.

The oligosaccharide
is attached to proteins by O-glycosidic and N-glycosidic
bonds.
is composed of fucose, N-acetyl glucosamine, galactose and
glucose.

Important Function of Oligosaccharide Chain


in Glycoprotein
1.

Oligosaccharide on surface of erythrocytes are


responsible for classification of blood groups.
are

2.
3.

called as blood group substances.

Oligosaccharides determine life span of proteins.


Cell-cell recognition depends on oligosaccharide
chains of glycoproteins.

Important Function of Oligosaccharide Chain


in Glycoprotein

Sialic Acids

Sialic acids are acyl derivatives of neuraminic acid.


Oligosaccharides

of some membrane glycoproteins


contains a terminal sialic acid.
Sialic acid is an important constituent of glycolipids
present in cell membrane and nervous tissue.

References

Rao NM. Medical Biochemistry. Revised second


Edition. New Age International Publishers 2006.

Smith C, Marks AD, Lieberman M. Marks Basic


Medical Biochemistry: A Clinical Approach,
2nd Edition.

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