All of the pharmacy and Health students use the materials

1. carbohydrates

2. Introduction
• Carbohydrates (sugars) are organic
compounds containing carbon, hydrogen and
oxygen. They could be grouped into three
types:
a. Monosaccharides (simple sugars): They are
simplest form of sugars, which cannot be further
hydrolyzed. They represent the building units
and hydrolytic end products of the more
complex carbohydrates.

3. Cont…
b. Oligosaccharides: These are the conjugates of
carbohydrates where 2-10 monosaccharide
units are linked to each other.
c. Polysaccharides: These are higher polymers of
carbohydrates and contain more than 10
monosaccharide units per molecule.

4. Importantance of Monosaccharides
• Glucose: an important source of physiological
energy.
• It is the building unit and end product of
hydrolysis of starch, dextrin, glycogen,
sucrose, maltose and lactose.
• It is the major body sugar; all
monosaccharides ingested may be converted
into glucose in the body and all can be
synthesized from it.

5. Cont…
• Mannose is a subunit in glycoproteins and
neuraminic acid. It is obtained by hydrolysis of
the plant mannosans and gums.
• Galactose is a subunit of the milk sugar,
lactose.
• It is also a constituent of the structure of
glycoproteins, glycolipids and
mucopolysaccharides

6. Cont…
• Fructose is the sweetest sugar. It is the main
sugar in bee's honey and fruits.
• It is obtained from insulin and sucrose
hydrolysis. It is called the semen sugar, since it
is present in seminal fluid and is the source of
energy for the spermatozoa

7. chemistry and properties of
carbohydrates
• Pyranose and furanose ring structures: The
stable ring structures of monosaccharides are
similar to the ring structures of either pyran (a
six-membered ring) or furan (a five-membered
ring).
• For glucose in solution, more than 99% is in
the pyranose form.

8. Structure of Monosaccharides
CHO
OH
H
H
HO
OH
H
OH
H
CH2OH
O
H
OH
H
OH
H
OH
H
OH
CH2OH
H
C
OH
H
H
HO
OH
H
H
CH2OH
O
OH
H
D-Glucose
Open chain form
D-Glucose
Fischer's hemiacetal cyclic form
(- and -anomers)
D-Glucose
Haworth's pyranose cyclic form
(Glucopyranose; - and -anomers)
CH2OH
O
H
HO
OH
H
OH
H
CH2OH
O
CH2OH
H
OH
CH2OH
OH
H
OH
H
D-Fructose
Open chain form
D-Fructose
Fischer's hemiacetal cyclic form
(- and -anomers)
D-Fructose
Haworth's furanose cyclic form
(Fructofuranose; - and -anomers)
CH2OH
OH
H
HO
OH
H
H
CH2OH
O





1
2
3
4
5
6
O
Furan
1
2
3
4
5
6
O
Pyran
HO
C
H
HO



OH
H
CH2OH
OH

9. Cont…
• Stereoisomerism: The total number of possible
stereoisomers of a compound is given by the
Vont Hoff’s rule, i.e., "2n", where; n is the number
of asymmetric carbon atoms
• e.g. Enantiomers (D- and L-isomers): These
isomers differ in distribution of H and OH groups
around the sub-terminal asymmetric carbon
atoms.
• D-form has the OH group to the right, whereas,
this group is on the left in the L-form.

10. Cont…
• Racemic mixture is a solution containing equal
concentration of D- and L-forms of a compound; the
mixture is optically inactive.
D-Glyceraldehyde
CHO
OH
H
CH2OH
CHO
H
HO
CH2OH
L-Glyceraldehyde

11. Cont…
• Optical Activity: It is the ability, conferred by
the asymmetric carbon to the sugar in
solution, to rotate the plane of the plane-
polarized light either:
• to the right when the sugar is dextrorotatory
(d or +), such as glucose, galactose and starch;
• or to the left when the sugar is levorotatory (l
or –), such as fructose and invert sugar.

12. Cont…
• All the monosaccharides except
dihydroxyacetone contain one or more
asymmetric (chiral) carbon atoms and thus
occur in optically active isomeric forms.
• The simplest aldose, glyceraldehyde, contains
one chiral center (the middle carbon atom)
and therefore has two different optical
isomers, or enantiomers

13. Susceptibility to oxidation and
reduction
• Glucose oxidized to Glucaric acid
• Galactose oxidized to Galactaric acid
• Glyceraldehyde is reduced into glycerol during
carbohydrate and lipid metabolism.
• Ribose is reduced to ribitol, a component of
the vitamin B2 (riboflavin).
• Glucose is reduced into sorbitol : A base in
several pharmaceutical preparations

14. Cont…
• Mannose gives rise to mannitol. Is injected
intravenously to reduce intracranial
hypertension in cases of meningitis, cerebral
hemorrhage or thrombosis
• Fructose is reduced into both sorbitol and
mannitol
• Galactose is reduced to galactitol or dulcitol.

15. 0ligosaccharides
• Disaccharides contain two monosaccharides
joined together by O-glycosidic linkage.
• The most common glycosidic linkage is
between C1 and C4 (14) .
• Other glycosidic linkages include; 16, 13,
12, 11 and 23.
• The linkage can be - or β- depending upon
the type of the anomeric carbon participating
in the linkage.

16. Cont…
• The disaccharide formed could be a reducing
(e.g., maltose, isomaltose, lactose and
cellobiose) or a non-reducing (e.g., sucrose
and trehalose) sugar

17. Cont…
-D-Glucose
O
H
OH
H
H
OH
H
OH
CH2OH
H
O
H H
OH
H
OH
H
OH
CH2OH
H
O
1
1
6
4

4

O
H
OH
H
H
OH
H
OH
CH2OH
H
O
H
OH
H
OH
H
OH
H
OH
CH2
H
O
1
1
4

4

O
H
OH
H
H
OH
H
OH
CH2OH
H
O
H H
OH
H
OH
H
OH
CH2OH
H
O
1
1
6
4

4

O
H
OH
H
H
OH
H
OH
CH2OH
H
O
H
OH
H
OH
H
OH
H
OH
CH2
H
O
1
1
4

4

-D-Glucose
-D-Glucose
-D-Glucose
Maltose
Isomaltose
Maltose
-D-Glucose
O
H
OH H
H
OH
H
OH
CH2OH
H
O
H OH
H
H
OH
H
OH
CH2OH
H
1
1 4
4

O

-D-Glucose
Cellobiose
-D-Glucose
O
H
OH
H
H
OH
H
OH
CH2OH
H
O
HOH2C H
CH2OH
OH
H
OH
H
1 2
4 
1

O
-D-Fructose
Sucrose

18. Polysaccharides
• Most carbohydrates found in nature occur as
polysaccharides, polymers of medium to high
molecular weight.
• Homopolysaccharides: Contain only a single type
of monomer;
• Heteropolysaccharides: contain two or more
different kinds.
• Some homopolysaccharides serve as storage
forms of monosaccharides that are used as fuels;

19. Cont…
Starch
• Contains two types of glucose polymer, amylose
and amylopectin .
• The former consists of long, unbranched chains of
D-glucose residues connected by (1n4) linkages.
• Amylopectin is highly branched.
• The glycosidic linkages joining successive glucose
residues in amylopectin chains are (1n4); the
branch points (occurring every 24 to 30 residues)
are (1n6) linkages

20. Structure of starch

21. Cont…
Glycogen
• Is the main storage polysaccharide of animal
cells. Like amylopectin, glycogen is a polymer
of (1n4)-linked subunits of glucose, with (1n6)-
linked branches.
• Glycogen is more extensively branched (on
average, every 8 to 12 residues) and more
compact than starch.
• Glycogen is especially abundant in the liver,

22. Structure of glycogen

23. Cont…
Inulin
• Is a polysaccharide of fructose (and hence a
fructosan).
• It is readily soluble in water and is used to
determine the glomerular filtration rate.
Dextrins
• Are intermediates in the hydrolysis of starch.

24. Cont…
Cellulose
• Is the chief constituent of the framework of
plants. It is insoluble and consists of β-D-
glucopyranose units linked by β(1 → 4) bonds to
form long, straight chains strengthened by cross-
linked hydrogen bonds.
• Cannot be digested by mammals because of the
absence of an enzyme that hydrolyzes the β
linkage.
• It is an important source of “bulk” in the diet.

25. Cont…
Chitin
• Is a structural polysaccharide in the
exoskeleton of crustaceans and insects and
also in mushrooms. It consists of N-acetyl-D-
glucosamine units joined by β (1 →4)-
glycosidic linkages

26. hetropolysaccharide
Proteoglycans
• Are macromolecules of the cell surface or
extracellular matrix in which one or more
glycosaminoglycan chains are joined covalently to
a membrane protein or a secreted protein.
• The glycosaminoglycan moiety commonly forms
the greater fraction (by mass) of the proteoglycan
molecule, dominates the structure, and is often
the main site of biological activity.
• Proteoglycans are major components of
connective tissue such as cartilage

27. Cont…
Lipopolysaccharides
• Are the dominant surface feature of the outer
membrane of gram-negative bacteria such as
Escherichia coli and Salmonella typhimurium.
• These molecules are prime targets of the
antibodies produced by the vertebrate
immune system in response to bacterial
infection

28. Digestion and absorption of
carbohydrates
• Most of the carbohydrates in the food stuffs are
complexed with proteins, lipids or even nucleic
acids to form the cellular matrix of the ingested
food.
• Saliva contains a very potent carbohydrate
splitting enzyme known as Salivary amylase.
• Hydrolyses starch and glycogen into maltose and
dextrins.
• Starch digestion by salivary amylase is
incomplete.

29. Cont…
• Salivary amylase becomes ineffective as soon as
the food reaches the stomach because of the
extreme acidic pH of 1 - 2.
• There is no carbohydrate splitting enzyme in the
stomach but HCl hydrolyses the disaccharides
particularly sucrose into glucose and fructose.
• As the food bolus enters into the duodenum, it is
exposed to the pancreatic juice which contains
the carbohydrate splitting enzyme pancreatic
amylase

30. Cont…
• Lactase (-galactosidase with a pH optima of 5.4
– 6.0) hydrolyzes lactose into glucose and
galactose.
• Cellulose and other dietary fibers pass as it is in
stools, increasing bulk of intestinal contents by
adsorbing water and stimulates peristaltic
movements.
• All the complex carbohydrates have been
converted into simpler monosaccharides. These
monosaccharides are almost completely
absorbed from the small intestine.

31. Glucose transporters

32. Disorders of carbohydrate
metabolism
Diabetes mellitus,
• Is caused by a deficiency in the secretion or
action of insulin
• There are two major clinical classes of
diabetes mellitus: type I diabetes, or insulin
dependent diabetes mellitus (IDDM), and type
II diabetes, or non-insulin-dependent diabetes
mellitus (NIDDM), also called insulin-resistant
diabetes.

33. Cont…
• Typically, its symptoms include polydypsia
(excessive thirst), polyuria (increased
frequency of urination), polyphagia (hunger),
glucosuria, lipemia and risk of developing
vascular disease, peripheral neuropathy,
impaired immunity, ketoacidosis and weight
loss particularly in type 1 diabetes mellitus.

34. Cont…
Causes of Diabetes Mellitus
• Absolute or relative insufficiency of insulin
• Insufficient secretion,
• Accelerated inactivation of insulin (as in
thyrotoxicosis).
• Defective processing of proinsulin into insulin
• Peripheral resistance to insulin due to defects in
its receptor and sub-receptor mediators.

35. Cont…
• Autoimmune destruction of pancreatic β-
cells, pancreatitis and pancreatic cancer.
• Viral infection, e.g., mumps and influenza.
• Over-eating, particularly of carbohydrates
with under activity (excessive carbohydrate
diet as a cause of diabetes mellitus is
detectable)

36. Types
 Are type 1, 2 and gestation diabetes
 Type 1 diabetes requires insulin for treatment and
hence the other name; Insulin Dependent Diabetes
Mellitus (IDDM).
 It represents <10% of all diabetic individuals.
 It is an autoimmune disease in which the body's own
immune system destroys β-cells of the pancreas,
rendering it unable to produce insulin.
• The disorder is detected at an early age (<15 years)

37. Cont…
• Type 2 diabetes represents ~90% of all diabetes cases
and presents with peripheral resistance to the effects of
insulin or a defect in insulin processing/secretion.
• The disorder, also known as non-insulin dependent
diabetes mellitus (NIDDM) because it does not requires
insulin as a treatment in most of cases.

38. Cont…
• It manifests at a later age (>40 years) that acquires it
the third name; Late or Adult-Onset Adult diabetes
and has a slow and silent onset.
• Gestational diabetes; and “other types” are very rare
and are caused by a single gene mutation.

39. The major metabolic effects of diabetes (particularly in type 1
diabetes) are:
• Decreased glucose uptake and utilization (low pace of
glycolysis).
• Decreased uptake of amino acids.
• Increased gluconeogenesis from amino acids and
glycerol.
• Enhanced glycogenolysis.
• Increased lipolysis.
• Ketogenesis.
• Cholesterol synthesis.
• Increased concentration of blood free fatty acids.
Metabolic changes in diabetes mellitus

40. Cont…
• Glucose accumulates in blood (hyperglycemia) that
exceeds the renal reabsorption limit (renal threshold)
and hence is excreted in urine in large amounts
(glucosuria).

41. Cont…
• Glycosylation of the proteins: Persistent
hyperglycemia during diabetes causes
spontaneous non-enzymatic glycosylation of
protein in blood vessels leading to thickening of
the basement membrane, particularly of the
small blood vessels (microangiopathy).
• The microvascular changes in the eye, kidney and
nerves leads to most of diabetes-associated
complications i.e. diabetic retinopathy, diabetic
nephropathy and diabetic neuropathy.

42. .
Fasting Plasma Glucose
Normal glucose tolerance <110 mg/dL (6.1 mM/L)
Impaired fasting glucose 110-125 mg/dL (6.1-6.9 mM/L
Diabetes mellitus >126 mg/dL (7.0 mM/L)
Diabetic 2 hr post-load during
OGTT
≥200 mg/dL
Table : Recommended cut-offs of plasma glucose levels.

43. Cont…
Lactase deficiency
• leads to lactose intolerance, an inherited or age-
dependent decline of enzyme expression or an
acquired medical problem due to intestinal diseases
such as sprue, colitis, kwashiorkor and gastroenteritis.
• Symptoms include abdominal cramps, diarrhea, and
flatulence on eating fresh and non-fermented milk
products. It is treated by consumption of live-culture
yogurt or -galactosidase therapy.

44. Glycolysis
• Derived from the Greek stem glyk-, "sweet," and the
word lysis, "dissolution."
• Glycolysis is the sequence of reactions that
metabolizes one molecule of glucose to two
molecules of pyruvate with the concomitant net
production of two molecules of ATP.

45. Cont…
• Glycolysis occurs in the cell cytoplasm of all tissues of
the body.
• Mammalian erythrocyte (RBCs): The red cells are
devoid of mitochondria and depend on glycolysis as
the main source of energy. RBCs are unique in that
about 90% of its total energy requirement is
provided by glycolysis.

46. Cont…
• Contracting muscles: Due to partial occlusion of blood
vessels by the muscular contraction, there is a
decrease in oxygen availability that creates temporary
anaerobic conditions. Most of the energy of the
rapidly contracting muscles comes from the anaerobic
oxidation of glucose through glycolysis.
• Cornea, lens and some parts of retina: They have a
limited blood supply and lack of mitochondria.
Therefore, needed energy is derived from glycolysis.

47. Cont…
• Glucose enters cells through specific transport proteins
and has one principal fate: it is phosphorylated by ATP
to form glucose 6-phosphate by enzyme hexokinase .
This step is notable for two reasons:
• (1) Glucose 6-phosphate cannot diffuse
• (2) The addition of the phosphoryl group begins to
destabilize glucose, thus facilitating its further
metabolism.

49. Hexokinase Glucokinase
Site: All tissues. Liver parenchymal and
pancreatic β-cells.
Affinity for glucose is
high (i.e., low Km, ~0.2
mM)
Low affinity (i.e., high Km,
5-10 mM) and traps
glucose by
phosphorylation for
storage in the liver
Allosteric inhibitor:
glucose-6-phosphate.
Glucose-6-phosphate
does not inhibit it.

50. Step 2
• The next step in glycolysis is the isomerization of
glucose 6-phosphate to fructose 6-phosphate.
• The isomerization of glucose 6-phosphate to fructose
6-phosphate is a conversion of an aldose into a
ketose. The reaction catalyzed by phosphoglucose
isomerase

51. Step 3
• Fructose 6-phosphate is phosphorylated by ATP to
fructose 1,6-bisphosphate (F-1,6-BP) by enzyme
phosphofructokinase-1

52. Step 4
• Splitting of fructose 1,6-bisphosphate into
glyceraldehyde 3-phosphate GAP) and
dihydroxyacetone phosphate (DHAP). By enzyme
aldolase

53. Step 5
• Glyceraldehyde 3-phosphate is on the direct pathway
of glycolysis, where as dihydroxyacetone phosphate is
not.
• These compounds are isomers that can be readily
interconverted: dihydroxyacetone phosphate is a
ketose, whereas glyceraldehyde 3-phosphate is an
aldose.
• The isomerization of these three-carbon
phosphorylated sugars is catalyzed by triose
phosphate isomerase

54. Step 6
• Conversion of glyceraldehyde 3-phosphate into 1,3-
bisphosphoglycerate (1,3-BPG), a reaction catalyzed by
glyceraldehyde 3-phosphate dehydrogenase
• 1,3-Bisphosphoglycerate is an acyl phosphate. Such
compounds have a high phosphoryl-transfer potential;
one of its phosphoryl groups is transferred to ADP in the
next step in glycolysis

55. Step 7
• Phosphoglycerate kinase catalyzes the transfer
of the phosphoryl group from the acyl
phosphate of 1,3 bisphosphoglycerate to ADP.
ATP and 3-phosphoglycerate are the products.

56. Step 8
• In the remaining steps of glycolysis, 3-
phosphoglycerate is converted into pyruvate
with the concomitant conversion of ADP into
ATP.

58. 2.7. Gluconeogenesis
• Gluconeogenesis , the synthesis of new glucose from
non-carbohydrates.
• Gluconeogenesis is an energy demanding process
• It utilizes the reverse pathway of glycolysis, with some
modifications

59. • A number of tissues are dependent upon blood
glucose as the only source of energy.
• These tissues include brain and nervous system,
RBCs, kidney medulla, Lens, cornea and some regions
of the retina, white and red skeletal muscles (under
anaerobic conditions), testes and leukocytes.
• For all tissues, glucose is required for pentose
pathway and glycolipids and glycoprotein synthesis.

60. Tissues active in gluconeogensis
• Liver – The major organ contributing to blood
glucose.
• Kidney Cortex, Brain, Skeletal muscle and other
Extrahepatic Tissues Gluconeogenesis is limited due
to deficiency of glucose-6-phosphatase. Glucose
from these tissues does not contribute to blood
glucose.

61. • Most of the step of glycolysis are reversible and hence
can be reversed for the synthesis of glucose.
• The Three steps of glycolysis that are Irreversible and
hence need to be bye-passed are the reactions
catalyzed by:
a) Pyruvate kinase,
b) Phosphofructokinase-1 and
c) Hexokinase.

63. Conversion of pyruvate to phosphoenol pyruvate
The glycolytic reaction activated by pyruvate kinase is by-
passed by the concerted action of two enzymes:
i) pyruvate carboxylase, and,
ii) phosphoenol pyruvate carboxykinase.

64. Phosphoenol Pyruvate (PEP) Carboxykinase
Converts oxaloacetate into phosphoenol pyruvate utilizing
GTP as phosphate donor and releasing H2O and CO2 again.

65. By-passing the irreversible phosphofructokinase-1 and gluco-/hexokinase reactions
requires the usage of two new irreversible enzymes; namely, the fructose-1,6-
diphosphatase and glucose-6-phosphatase.