This document discusses carbohydrate chemistry, metabolism, and regulation. It covers: - The structure and classification of carbohydrates including monosaccharides, disaccharides, oligosaccharides, and polysaccharides. - The digestion of carbohydrates in the mouth, stomach, and small intestine by enzymes that break down polysaccharides and oligosaccharides into monosaccharides like glucose, which are then absorbed. - The metabolism of glucose through three main pathways: glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation to generate cellular energy. Glycolysis occurs anaerobically in the cytosol and aerobically in the mitochondria. - The regulation of blood glucose levels through pathways

1. Chemistry and Metabolism of
Carbohydrates

2. Chapter content
Structure & classification of carbohydrates
Digestion & absorption of carbohydrates
Metabolism of carbohydrates:
• Glycolysis
• Oxidation of pyruvate
• Pentose phosphate pathway
• Glycogen metabolism
• Gluconeogenesis
Regulation of blood glucose

3. Introduction
Carbohydrates are the most abundant organic
molecules in nature.
They have a wide range of functions, including
providing a significant fraction of the dietary
calories for most organisms, acting as a storage
form of energy in the body, and serving as cell
membrane components that mediate some forms
of intercellular communication.
Carbohydrates also serve as a structural component
of many organisms, including the cell walls of
bacteria, the exoskeleton of many insects.

4. Glucose is the universal fuel for human cells. Every
cell type in the human is able to generate
adenosine triphosphate (ATP) from glycolysis, the
pathway in which glucose is oxidized and cleaved to
form pyruvate.
The importance of glycolysis in our fuel economy is
related to the availability of glucose in the blood, as
well as the ability of glycolysis to generate ATP in
both the presence and absence of O2.

5. Glucose is the major sugar in our diet and the sugar
that circulates in the blood to ensure that all cells
have a continuous fuel supply. The brain uses
glucose almost exclusively as a fuel.
Carbohydrates or their hydrolytic products are
either polyhydroxy aldehydes or polyhydroxy
ketones. Thus, each carbohydrate molecule carries
two or more alcoholic OH groups and one or more
ketone groups. Example,

6. 1. Some carbohydrates such as glucose, trehalose,
glycogen, starch and dextrin serve to produce energy.
Some of them like starch and glycogen are stored in
the cell for future use in energy production.
2. Some other carbohydrates such as chitin,
hyaluronic acid and chondroitin sulphate constitute
molecular component of cellular and extra cellular
structural elements.
3. The sugars, ribose and deoxyribose are essential
constituents of nucleotides and nucleic acids.
Functions of carbohydrates

7. 4. Carbohydrates form complexes like glycoproteins
and mucoproteins with proteins and glycolipids with
lipids; many of these are structural components while
some glycoproteins like pituitary thyrotropin serves as
hormones.
5. Fatty acids and amino acids can be synthesised
in the body from metabolic products of carbohydrates.
6. Lactose of milk serves as an important nutrient
for all young mammals.
7. Cardiac glycosides are carbohydrates-steroid
complexes having important pharmacological actions
on the heart.
8. Some antibiotics like streptomycin are also
glycosides with carbohydrate residue in their
molecules.

8. Classification of carbohydrates
Carbohydrates are classified broadly as
monosaccharides and compound carbohydrates.
MONOSACCHARIDES: These are the simplest
carbohydrates and cannot be hydrolyzed further into
smaller carbohydrate molecules.
They are again classified according to the number of
carbons in the molecule:
a) Trioses (C3 H6 O3) – glyceraldehyde and
dihydroxyacetone
b) Tetroses (C4 H8 O4)- erythrose and erythrulose
c) Pentoses (C5 H10 O5) – ribose and ribulose
d) Hexoses (C6 H12 O6) – glucose and fructose
e) Heptoses (C7 H14 O7) - Sedoheptulose

9. Sedoheptulose

10. COMPOUND CARBOHYDRATES: These are made of
two or more monosaccharides interlinked by
glycosidic bonds. They can, therefore, be
hydrolyzed into as many monosaccharide
molecules. They are classified as follows:
a) Oligosaccharides: They are composed of
several (usually 2-10) monosaccharide molecules
joined by glycosidic bonds. They are further
classified into:
1. Disaccharides- formed by the union of 2
monosaccharide molecules. Eg. Sucrose, maltose
and lactose.

12. 2. Trisaccharides- composed of 3 monosaccharide
molecules. Eg. Raffinose

13. b) Polysaccharides: They are macromolecular
carbohydrates each composed of many (>10)
monosaccharide molecules linked by glycosidic bonds.
Polysaccharides have two subclasses:
1. Homoglycans- starch and glycogen, each of
which is composed of many molecules of same
monosaccharide.
Starch : Starch is a mixture of glucans that plants
synthesize as their principal food reserve. It is
deposited in the cytoplasm of plant cells as insoluble
granules composed of alpha-amylose and amylopectin.
Alpha-Amylose is a linear polymer of several thousand
glucose residues linked by bonds.

15. Glycogen:

16. 2. Heteroglycans- such as heparin and hyaluronic acid, each
made of more than one type of monosaccharides

21. Digestion and absorption
Dietary carbohydrates principally consist of the
polysaccharides: starch and glycogen. It also contains
disaccharides- sucrose, lactose and maltose and in
small amounts monosaccharides like fructose.
1. Digestion in mouth: Digestion of carbohydrates
starts at the mouth, where they come in contact with
saliva during mastication. Saliva contains a
carbohydrate splitting enzyme called salivary amylase
(Ptyalin). The enzyme hydrolyzes alpha 1-4 glycosidic
linkages at random deep inside polysaccharide
molecule like starch, glycogen and dextrins, producing
smaller molecules maltose, glucose and trisaccharide
maltotriose. Ptyalin action stops in stomach when pH
falls to 3.0.

22. 2. Digestion in stomach: Practically no action.
No carbohydrate splitting enzymes available in
gastric juice. Some dietary sucrose may be
hydrolyzed to equimolar amounts of glucose and
fructose by HCL.
3. Digestion in duodenum: Food bolus reaches
the duodenum from stomach where it meets
the pancreatic juice. This contains pancreatic
amylase which hydrolyzes alpha 1-4 glycosidic
linkages situated well inside polysaccharide
molecule.

23. 4. Digestion in small intestine:
Intestinal amylase: They hydrolyze terminal alpha
1-4 glycosidic linkages in polysaccharide and
oligosaccharide molecules liberating free glucose
molecule.
Lactase: It hydrolyzes lactose to glucose and
galactose.
Isomaltase: It catalyzes hydrolysis of alpha 1-6
glycosidic linkage at the branching points and
producing maltose and glucose.
Maltase: This hydrolyzes the alpha 1-4 glycosidic
linkages between glucose units in maltose
molecule liberating two glucose molecules.

26. Absorption of carbohydrate
It is observed from the above that carbohydrate digestion is
complete when the food materials reach small intestine and
all complex dietary carbohydrates like starch and glycogen
are ultimately converted to simpler monosaccharides.
Mechanism of absorption:
a) Simple diffusion: This is dependent on sugar
concentration gradients between the intestinal, mucosal cells
and blood plasma. All the monosaccharides are probably
absorbed to some extent by simple passive diffusion

27. b) Active transport mechanism: Glucose and galactose
are absorbed very rapidly and hence it has been
suggested that they are absorbed actively and it requires
energy. Energy is provided by ATP, by the interaction of
the sodium dependent sugar carrier and the sodium
pump, actively transported sugars are concentrated
within the cell without any back leakage of the sugar
into the lumen.
• It is believed that sodium binding by the carrier
protein is pre-requisite for glucose binding.
• Sodium binding changes the conformation of the
protein molecule, enabling the binding of glucose to
take place and thus the absorption to occur.

29. Carbohydrate – Metabolism
The catabolic oxidation of glucose, to provide cellular
energy, occurs principally through three ‘linked’
catabolic pathways:
• • Glycolysis
• • Tricarboxylic acid cycle (TCA cycle)
• • Mitochondrial electron transfer/oxidative
phosphorylation.

30. Glycolysis
Glucose and glycogen are anaerobically catabolized in the
cytosol of cell to pyruvate and lactate through glycolysis. It is
the principal energy generating pathway in erythrocytes,
white striated muscle fibres, brain, skin, renal medulla and
gastro intestinal tract.
Glycolysis begins with the phosphorylation of glucose to
glucose 6-phosphate (glucose-6-P) by hexokinase (HK). In
subsequent steps of the pathway, one glucose-6-P molecule
is oxidized to two pyruvate molecules with generation of
two molecules of NADH.
A net generation of two molecules of ATP occurs through
direct transfer of high-energy phosphate from intermediates
of the pathway to ADP. Pyruvate is then oxidized completely
to CO2 by pyruvate dehydrogenase in the TCA cycle.

31. When cells have a limited supply of oxygen (e.g., kidney medulla), or few or no
mitochondria (e.g., the red cell), or greatly increased demands for ATP (e.g.,
skeletal muscle during high-intensity exercise), they rely on anaerobic glycolysis
for generation of ATP. In anaerobic glycolysis, lactate dehydrogenase oxidizes the
NADH generated from glycolysis by reducing pyruvate to lactate.
• In each cell, glycolysis is regulated to ensure that ATP homeostasis is
maintained, without using more glucose than necessary. In most cell types,
hexokinase (HK), the first enzyme of glycolysis, is inhibited by glucose 6-
phosphate. Thus, glucose is not taken up and phosphorylated by a cell unless
glucose-6-P enters a metabolic pathway, such as glycolysis or glycogen
synthesis. The control of glucose-6-P entry into glycolysis occurs at
phosphofructokinase-1(PFK-1), the rate-limiting enzyme of the pathway.
• PFK-1 is allosterically inhibited by ATP and allosterically activated by AMP.
AMP increases in the cytosol as ATP is hydrolyzed by energy-requiring
reactions.

37. Oxidation of pyruvate
Pyruvate Metabolism

42. It is the formation of glucose from non-carbohydrate materials
in liver and renal cortex. Lactate and pyruvate are quantitatively
the largest source of glucose in gluconeogenesis, particularly in
intense exercise. Next comes the glucogenic amino acids such as
glycine and alanine, during starvation, gluconeogenesis takes
place mainly from amino acids.

44. Glycogen Metabolism
GLYCOGENESIS
Glycogenesis is the synthesis of glycogen from glucose in the cytosol. Mainly the liver and
muscles and to lesser extent, many other tissues, except mature erythrocytes, brain and
kidneys, carry out glycogenesis.
Glucose (1) glucose 6 -phosphate (2) glucose 1-phosphate (3)
UDP-glucose (4) glycogen amylose (5) glycogen
(1) Hexokinase or glucokinase
(2) Phospho glucomutase
(3) UDP-glucose pyrophosphorylase
(4) Glycogen synthase
(5) Branching enzyme

45. Glycogenolysis
• Glycogenolysis is a catabolic process; the breakdown of glycogen to
glucose units.
• Glycogen is principally stored in the cytosol granules of -
• Liver
• Muscle

46. Glycogen Function
• In liver – The synthesis and breakdown of glycogen is
regulated to maintain blood glucose levels.
• In muscle - The synthesis and breakdown of glycogen
is regulated to meet the energy requirements of the
muscle cell.

47. , alpha 1,4  alpha 1,4 glucan transferase,
amylo 1,6 glucosidase

48. Hexose Monophosphate Pathway

50. Inherited disorders of carbohydrate metabolism
Glycogen storage diseases
These are a group of inherited disorders associated with glycogen metabolism,
characterized by deposition of normal type and quantity of glycogen in the tissues.
TYPE-1 -Von Gierke’s disease
• Enzyme deficient: Glucose 6-phosphatase. The enzyme is absent in liver cells and also
in intestinal mucosa.
• Inheritance: Autosomal recessive.
- Liver cells, intestinal mucosa and cells of renal tubular epithelial cells are loaded with
glycogen which is normal in structure but metabolically not available.
- Since very little glucose is derived from the liver, children with this disease tend to
develop hypoglycaemia. Glucose cannot be converted to glucose 6-phosphate due to
deficiency of the enzyme and it is locked in the cells.

51. Persistent hypoglycaemia can have two effects:
• Hypoglycaemia inhibits insulin secretion which in
turn inhibits protein synthesis which causes stunted
growth (dwarfism).
• Hypoglycaemia stimulates secretion of
catecholamines, which cause muscle glycogen to
break down producing lactic acid and lactic acidosis.

52. TYPE-II: Pompe’s disease
Enzyme deficient: Acid maltase
• Enzyme is present in lysosome and catalyzes break down of
oligosaccharides.
• Inheritance: Autosomal recessive
- Glycogen structure is normal. Generalized involvement of organs is
seen including heart, liver, smooth and striated muscles.
Nearly all tissues contain excessive amount of normal glycogen.
- Cardiomegaly is seen. Muscle hypotonia leading to muscle weakness.
- Infants usually die of cardiac failure and bronchopneumonia. Death
usually occurs before 9 months.

53. TYPE-III: Limit Dextrinosis (Forbe’s disease)
• Enzyme deficiency: Debranching enzyme
• Inheritance: Autosomal recessive
Glycogen structure: Limit dextrin type, abnormal, short
outer chains. Organs involved are liver, heart and
muscle.
- Hepatomegaly, moderate hypoglycaemia, acidosis,
progressive myopathy.
- Survive well to adult life.

54. TYPE-IV: Amylopectinosis (Andersen’s disease)
• Enzyme deficiency: Branching enzyme
• Inheritance: Not definitely known
- Glycogen deposited is abnormal type, main organs
affected are liver, heart, muscle and kidney.
- Hepatomegaly, splenomegaly, ascites, moderate
hypoglycaemia, nodular cirrhosis of liver and hepatic
failure. Enzyme deficiency can be demonstrated in
leucocytes and liver.
- Usually fatal. Longest survival reported as 4 years.

55. TYPE-V: Mc Ardle’s disease:
• Enzyme deficiency: Muscle phosphorylase
• Inheritance: Autosomal recessive
- Glycogen deposited is normal in structure; organs
involved is skeletal muscle
- Muscle cramps on exercise, pain and weakness and
stiffness of muscles. No lactate is formed. Muscle
recovers on rest, due to utilization of FA for energy.

56. TYPE-VI: Her’s disease
• Enzyme deficiency: Liver phosphorylase
• -glycogen deposited is normal in structure; organs
affected are mainly liver and leucocytes.
• Hepatomegaly, mild to moderate hypoglycaemia and
mild acidosis.