The document discusses carbohydrates, including their definition, classification, properties, and forms. Carbohydrates are classified as monosaccharides, disaccharides, oligosaccharides, or polysaccharides depending on the number of monosaccharide units. Monosaccharides like glucose are the most basic units and important biologically. Glucose exists in both open-chain and cyclic forms, and can exhibit mutarotation between alpha and beta anomer configurations. Carbohydrates serve important structural and energy storage functions in living organisms.

2. CARBOHYDRATES
-Definition
-Classification (mono, di, poly
saccaharide)
-Isomerism
-Properties
-Forms of carbohydrates.

3. • The term carbohydrates refers to hydrates
of carbon as in the empirical formulas
contain approx. one molecule of water per
carbon atom.
• Carbohydrates are aldehyde or ketone
compounds with multiple hydroxyl groups.

4. • They make up most of the organic
matter on earth because of their
multiple roles in all forms of life.

6. • First, Carbohydrates serve as energy
stores, fuels, and metabolic intermediates.
• Prime fuel for the generation of energy.
EX 1: Starch in plants.
EX 2: Glycogen in animals.

7. ATP, the universal currency of free energy,
is a phosphorylated sugar derivative.

8. Second, ribose and deoxyribose sugars
form part of the structural framework of
DNA and RNA.
• The conformational flexibility of these
sugar rings is important in the storage and
expression of genetic information.

9. Third, polysaccharides are structural
elements in the cell walls of bacteria and
plants.
EX: Cellulose, the main constituent of plant
cell wall, is the most abundant organic
compound in the biosphere.

10. Fourth, carbohydrates are linked to many
proteins and lipids.
EX: Sugar units of glycophorin give red cells
a highly polar anionic coat.
EX: In the form of glycoprotein, these are
key participants in cell recognition during
development.

11. Classification
•
Monosaccharide.
•
Disaccharides
•
Oligosaccharides
•
Polysaccharides

12. MONOSACCHARIDES
• Carbohydrates that cannot be hydrolyzed into
simpler carbohydrates.
• They may be classified as depending upon the
number of carbon atoms.
• Trioses,
• Tetroses,
• Pentoses,
• Hexoses
• Heptoses

15. Monosaccharides are reduced to sugar
alcohols by reduction of aldehyde and
ketone groups.
• They are used in food made for diabetics
as they have half the energy production as
sugars because these are poorly
absorbed.
Ex: Glucose→ galactol

16. Disaccharide – condensation of two
monosaccharide units produces a
disaccharides.
• The O – glycosidic bond is formed
between the monosaccharide units.
• Three highly abundant disaccharides are
sucrose, lactose and maltose.

21. • Oligosaccharides – are condensation
products of three to ten monosaccharides.
EX: Dextran and Dextrins.
EX: Integral membrane proteins contain
covalently attached oligosaccharides on
their extracellular surface.

22. EX: Secreated proteins like antibodies and
clotting factors also contain
oligosaccharide units which are either
attached via O – glycosidic linkages or N –
glycosidic linkages.

24. Polysaccharides
• Condensation products of more than ten
monosaccharide units.
EX: Starch and glycogen which may be
linear or branched polymers.
EX: Cellulose (glucose polymer) and inulin
(fructose polymer)
↓

25. MONO SACCHARIDES
• Biomedically glucose is the most
important monosaccharide.
Structure
• It’s structure can be projected by Fisher
represented both
• as a straight chain and
• as a cyclic

26. • These are projected by Haworth structure.
• The straight chain accounts for some of
the properties of glucose like reduction,
oxidation etc.

27. • A cyclic structure is thermodynamically
favoured and accounts for most properties
of glucose.
• Cyclical structure is formed by reaction
between the aldehyde group and a
hydroxyl group.

28. • This structure has carbon atoms in two
orientations - (a) axial (b) equatorial axial
bonds are nearly per pendicular to the
average plane of the ring. Equatorial
bonds are parallel to this plan.

32. The ring structure adopts chair and boat
conformations

34. ISOMERISM
• Compounds with same chemical formula
with different structural arrangement
around a-symmetric carbon atoms.
• Isomers depend upon number of asymmetric carbon atoms in a compound.

35. • The formula to calculate isomers of a
compound is 2n where n is the number of
a-symmetric carbon atoms.
EX: glucose with four asymmetric carbon
atoms can form sixteen (16) isomers.
EX: Glyceraldehyde has a single asymmetric carbon and so has two
isomers.

36. TYPES
• D and L isomerism
• Pyranose and furanose ring structure
• Alpha and beta anomers
• Epimers
• Aldose-ketose isomerism

37. D and L isomerism
• Configuration of H and OH groups around
the 2nd carbon atom of glyceraldehyde
determine the D and L varieties of isomers.
• D and L isomers are mirror images of each
other and are called enantiomers.
• This carbon atom is the reference carbon
and is also called penultimate carbon.

40. • The orientation of the H and OH groups at
carbon no.5 in glucose determines
whether sugar belongs to D or L series.
• When OH group is on the right of this
carbon, the sugar is the D isomer. When it
is on the left, it is the L-isomer.

41. • Most monosaccharides occurring in
mammals are D sugars.
• Our body can metabolize only D-sugars.

42. Stereoisomer
• Having same structural formula but differ in
spatial configuration.
• No of possible stereoisomers depend upon
the no of asymmetric carbon atom.
• Formula for no of stereoisomer is 2 n .

43. • Where n is the no of stereoisomer.
• Diastero-isomers depend on the
configurational changes on C2, C3 & C4.
• It will produce MS like glucose, mannose,
galactose etc.

44. Optical isomerism
• The presence of asymmetric carbon
atoms also confers optical activity on the
compound.
• It is rotation of plane polarized when
passed through a sugar solution of an
isomer.

45. • If the rotation is towards right then the
compound is said to be dextrarotatory (+).
• If it rotates to the left then the compound is
said to be levorotatory (-).

46. • The direction of rotation is independent of
the structure of the sugar.
• Glucose is dextrorotatory and so is at
times referred as dextrose.
• D glucose is dextrorotatary, represented
as D (+).
• D-Fructose is levorotatory so is
represented as D (-).

47. • Equimolecular mixture of optical isomers
has no net rotation and so are referred as
recemic mixture.

48. Mutarotation
• A freshly prepared solution of D-glucose at
room temperature has specific rotation of
polarized light + 112 degree.
• After 12-18 hrs it changes to +52.5
degree.

49. • It initial crystallization is at 98 degree and
than solubalized the specific rotation will
be + 19 degree.
• Within few hours, it will also change to +
52.2 degree.

50. • This change in rotation with time is called
mutarotation.
• It depends on the fact that D-glucose has
2 anomers α and ß.

51. • At equilibrium 1/3rd mols are α type and
2/3rd are ß variety.
• The difference of α and ß forms is
dependent on the first carbon atom only.

52. PURANOSE AND FURANOSE RING
STURCTURE
• Ring structure of monosaccharides are
similar to the ring structures of either
• pyran (six-memberd ring) or
• furan (a five memberd ring).
• In glucose solution 99% is pyranose form.

55. Alpha and Beta anomers
• Cyclization of sugar creates an anomeric
carbon generating alpha and beta
configuration of the sugar.
• These are referred as anomers of each
other.

56. • Alpha and beta are not the mirror images.
• Ring structure of aldose is hemiacetal
• Ring structure of ketose is hemiketal.
• In solution, cyclic structure is retained but
isomerism occurs only around C1

57. • It gives a mixture of α-glucopyranose
(38%) and β-glucopyranose (62%).
• Less than 0.3% by α and β anomers of
glucofuranose.
• The specific rotation [α] D is defined as
the observed rotation of light of wave
length 589 nm passing through 10 cm of a
1g/ml of a sample.

58. • The specific rotation of α anomers is +112
degrees and β anomers is + 18.7 degrees.
This rotation of light keeps changing in a
freshly prepared solution.

61. EPIMERS
• Epimers are isomers differing as a result
of variations in configuration of the OH
and H on carbon atoms 2, 3 and 4 of
glucose are known as epimers.
• Biologically most important epimers of
glucose are mannose (carbon no.2) and
galactose (carbon no.4).

62. • Eight different monosaccharides are
produced by this configurational change
around C2, C3 and C4.
EX : Glucose Idose, Talose, Allose and
Altrose etc.
• Molecular formula C6H12O6 represents 16
different monosaccharide units due to
spatial arrangement.

65. Aldose-Ketose isomerism
• Fructose has the same molecular formula
as glucose but differ in its structural
formula as fructose has a potential keto
group in position no.2 (anomeric carbon of
fructose)
• Glucose has a potential aldehyde group in
position no.1 (anomeric carbon of
glucose)

66. REACTION OF MONOSACCHARIDES
Reduction:• Sugars are reduced under specific
conditions of pressure and temperature to
form alcohol.
• Reduction of hydrogen atoms leads to
formation of alcohols.
• Aldoses form one alcohol.
• ketoses forms two alcohols due to
appearance of a new a-symmetric carbon
atom during the process

67. • Glucose, fructose and mannose forms 1,2
enediol
• Galactose
dulcitol
• Ribose
ribitol
• Enediols are highly reactive, so sugars are
powerful reducing agents in alkaline
medium and form the basis of benedicts
test.

68. • Certain strains of bacteria use these alcohols
as source of energy and are used to identify
colonies of bacteria.
• Presence of these alcohols in tissues cause
osmotic imbalance resulting in accumulation
of fluid in them,
EX; Cataract of lens

71. Oxidation
• Under mild oxidation conditions, Aldehyde
group is oxidized to carboxyl group to
produce aldonic acid
glucose
gluconic acid
mannose
mannonic acid
galactose
galactonic acid

72. • when aldehyde group is protected then the
molecule is oxidised at the last carbon and CooH
group is formed at this carbon to form uronic acid
glucose
glucoronic acid
mannose
mannuronic acid
galactose
galacturonic acid

73. • Glucoronic acid is used by the body for conjugation
with insoluble molecules to make them soluble in
water and for synthesis of heteropoly saccharides.
• Under strong oxidation conditions the 1st and last
carbon atoms are simultaneously oxidized to to form
dicarboxylic acids called as saccharic acids
glucose
glucosaccharic acid
mannose
mannaric acid
galactose
mucic acid

74. FORMATION OF GLYCOSIDES
• When a hemi-acetal group is condensed
with either an alcohol or phenol group, it
forms a glycoside.
• Some of the glycosides are important
medically as drugs.

75. • Condensation is between the hydroxyl
group of the anomeric carbonof
monosaccharide and a second compound
that may or may not be another
monosaccharide
EX glycone or aglycone.

77. • If the hemiacetal portion is glucose the
resulting compound is a glucoside.
• If it is a galactose then it is a galactoside
and so on.
• If the second group is an amine so Nglycosidic bond is formed.
EX: bond between adenine and ribose in
nucleotides such as ATP

79. • Glycosides are widely distributed in
nature.
• a-glycone may be methanol, glycerol,
sterol, phenol or a base such as adenine.
• Most important are cardiac glycosides
which contain steroids as the aglycone.

80. • Also ouabain is inhibitor of Na-K+ ATpase
of cell membranes.
• Other glycosides include antibiotics like
streptomycin.

81. Ester formation:
• Hydroxyl group of sugar can be esterified
to form acetates, propionate, benzoate etc
• Sugar phosphate are biologically
important in glucose meta as
intermediates

82. Sugar
Source
Biochemical and Clinical
importance
D-Ribose
Nucleic acids and
metabolic intermediate
Structural component of nucleic
acids coenzymes, including ATP,
NAD(P), and flavin coenzymes
D-Ribulose
Metabolic intermediate
Intermediate in the pentose
phosphate pathway
D-Arabinose
Plant gums
Constituent of glycoproteins
D-Xylose
Plant gums,
proteoglycans,
glycosaminoglycans
Constituent of glycoproteins
L-Xylulose
Metabolic intermediate
Excreted in the urine in essential
pentosuria

83. Sugar
Source
Biochemical Importance
Clinical Significance
D-Glucose
Fruit juices, hydrolysis
of starch, cane or beet
sugar, maltose and
lactose
The main metabolic fuel for
tissues; “blood sugar”
Excreted in the urine
(glucosuria) in poorly
controlled diabetes
mellitus as a result of
hyperglycemia
D-Fructose
Fruit juices, honey,
hydrolysis of cane or
beet sugar and inulin,
enzymic isomerization
of glucose syrups for
food manufacture
Readily metabolized either
via glucose or directly
Hereditary fructose
intolerance leads to
fructose accumulation
and hypoglycemia
D-Galactose
Hydrolysis of lactose
Readily metabolized to
glucose; synthesized in the
mammary gland for
synthesis of lactose milk. A
constituent of glycolipids
and glycoproteins
Hereditary
galactosemia as a
result of failure to
metabolize galactose
leads to cataracts
D-Mannose
Hydrolysis of plant
mannan gums
Constituent of
glycoproteins

84. Sugar
Composition
Source
Clinical Significance
Isomaltose
O-α-D-glucopyranosyl(1→6)- α-Dglucopyranose
Enzymic hydrolysis of
starch (the branch points
in amylopectin)
Maltose
O-α-D-glucopyranosyl(1→4)- α-Dglucopyranose
Enzymic hydrolysis of
starch (amylase);
germinating cereals and
malt
Lactose
O-α-D-galactopyranosyl(1→4)-β-D-glucopyranose
Milk (and many
pharmaceutical
preparations as a filler)
Lack of lactase (alactasia)
leads to lactose intolerance
– diarrhea and flatulence;
may be excreted in the urine
in pregnancy
Lactulose
O-α-D-galactopyranosyl(1→4)-β-D-fructofuranose
Heated milk (small
amounts), mainly synthetic
Not hydrolyzed by intestinal
enzymes, but fermented by
intestinal bacteria, used as
a mild osmotic laxative
Sucrose
O-α-D-glucopyranosyl(1→2)-β-Dfructofuranoside
Cane and beet sugar,
sorghum and some fruits
and vegetables
Rare genetic lack of sucrase
leads to sucrose intolerance
– diarrhea and flatulence
Trehalose
O-α-D-glucopyranosyl(1→1)- α -Dglucopyranoside
Yeasts and fungi; the main
sugar of insect hemolymph

85. Sucrose (cane sugar)
Present in honey and fruits.
Hydrolysis of sucrose (O/R +66.5) will produce
• Glucose (+52.5)
• Fructose (-920).
• Products will change dextrorotation to
Levorotation-----called invert sugar.

86. • Enzyme used is invertase.
• It is a non-reducing sugar as free sugar
groups are not available for reduction
present at C4.

87. Lactose (milk sugar)
• Reducing disaccharide.
• Hydrolyzed by lactase to form glucose and
galactose.
• Because of ß glycosidic linkage b/w
galactose and glucose.
• It can be hydrolyzed by ß glycosidase.
• Forms osazone “hedgehog”.

88. Maltose
• Reducing disaccharide.
• It forms petal shaped crystals of maltoseosazone.
• On hydrolysis it gives 2 glucose residues
with α1→4 glycosidic linkage.

89. • It is a product of salivary amylase action
upon starach.
• Isomeric form is isomaltose (α1→6).
• Partial hydrolysis of glycogen and starch
produces isomaltose due to action of
oligo- 1 →6 glucosidase.

90. Polysaccharides
• Polymerized products of many MSs.
• Classified as
• Homopolysaccharides or homoglycans
Examples:
Starch
Glycogen
Cellulose

91. • Heteropolysaccharides or heteroglycans
or glycosaminoglycans.
Examples
• Agar (galactose, glucose and other
sugars).

92. • Hyaluronic acid (repeated units of N-acetyl
glucosamine, 4 glucoronic acid)
• Heprin (repeated units of sulfated
glucosamine, 4L iduronic acid, which is
the oxidized form of idose--------a 5 th
isomer of glucose).

96. Starch:
• Most important dietary source of CHO.
• Has 2 main constituents i.e.
• Amylose (13-20%) has a non branching
helical structure.
• Amylopectin (80-85%) and consist of
branched chain composed of 24-30
glucose residues and linkages in the chain
at branched point is 1-6.

97. • Each branch consist of 15-18 glucose
units.
• A branch is after every 8-9 glucose units.
• On hyrdrolysis, it gives glucose.

98. Glycogen (animal starch)
• Stored polysaccharide in animals especially
in liver and muscle.
• It is more branched and more compact than
amylopectin of starch.
• Its MW is high. It is therefore exert very little
O/P.
• Hence liver cell can store glycogen in a
small space.

99. Cellulose
• Most abundant organic material in nature.
• Made up off glucose units with ß 1→4
linkages.
• It has a straight line structure with no
branch.

100. • Cannot be digested in human, as they
lack cellulase enzyme.
• Herbivores animals and termites can
digest cellulose with the help of intestinal
bacteria containing cellulase enzymes.

101. Inulin:
• it is composed of D-fructose units with
repeated 1-2 linkages.
• It is stored CHO present in tubers, onion
and garlic etc.
• Clinically use to find renal clearance value
and GFR.

102. Dextrans:
• Intermediates in hydrolysis of starch.
• Highly branched with 1-6 and 1-4 and 1-3
linkages.
• Used as plasma expanders I/V for
treatment of hypovalemic shock as they
donot leak out of BV, due to high MW.

103. • A- Glycosaminoglycans
(mucopolysaccharides, GAGs)
• At least seven glycosaminoglycans
(GAGS) (hyaluronic acid, chondroitin
sulfate, keratan sulfates I and II, heparin,
heparan sulfate, and dermatan sulfate)
are found in body.

104. • Structure: A GAG is an unbranched
polysaccharide made up of repeating
disaccharides with following structural
components

105. •
One component a GAG is always an
amino sugar, either D‑glucosamine or
D‑galactosamine.
•
The other component of the repeating
disaccharide (except in the case of
keratan sulfate) is a uronic acid, either
L‑glucuronic acid (GlcUA) or its 5'‑epimer,
L,‑iduronic acid (IdUA).

106. • With the exception of hyaluronic acid,
all the GAGS contain sulfate groups,
either as O‑esters or as N‑sulfate (in
heparin and heparan sulfate).

107. • Definition: Glycosaminoglycans (GAGs)
are large complexes of negatively
charged heteropolysaccharide chains.
They are generally associated with a
small amount of protein, forming
proteoglycans, which typically consist
of over 95 percent carbohydrate.

108. • The seven GAGs as mentioned in the
previous slide differ from each other in a
number of the following properties
• amino sugar composition
• uronic acid composition
• linkages between these components
• chain length of the disac-charides

109. • the presence or absence of sulfate groups
and their positions of attachment to the
constituent sugars
• the nature of the core proteins to which
they are attached
• the nature of the linkage to core protein
• their tissue and subcellular distribution
• and their bio-logic functions.

110. • Tissue distribution of GAGs : As the
ground or packing substance, they are
associated with the structural elements of
the tissues such as bone, elastin, and
collagen.

111. • Their property of holding large quantities of
water and occupying space, thus cushioning
or lubricating other structures, is assisted by
the large number of ‑OH groups and
negative charges on the molecules, which,
by repulsion, keep the carbohydrate chains
apart.

112. • Examples are hyaluronic acid,
chondroitin sulfate, and heparin, blood
group polysaccharides, blood serum
mucoids

113. Building blocks of GAGs
C-5 epimer of glucuronic acid

114. • Relationship between
glycosaminoglycan structure and
function
• Because of their large number of
negative charges, these
heteropolysaccharide chains tend to be
extended in solution.

115. • They repel each other and are
surrounded by a shell of water
molecules. When brought together,
they "slip" past each other, much as
two magnets with the same polarity
seem to slip past each other.

116. • This produces the "slippery"
consistency of mucous secretions and
synovial fluid.
• When a solution of
glycosaminoglycans is compressed,
the water is "squeezed out" and the
glycosaminoglycans are forced to
occupy a smaller volume.

117. • When the compression is released, the
glycosaminoglycans spring back to
their original, hydrated volume because
of the repulsion of their negative
charges. This property contributes to
the softness of synovial fluid and the
vitreous humor of the eye

118. Relationship between
glycosaminoglycan structure and
function
When a solution of
glycosaminoglycans is compressed,
the water is "squeezed out" and the
glycosaminoglycans are forced to
occupy a smaller volume.
When the compression is released, the
glycosaminoglycans spring back to their
original, hydrated volume because of the
repulsion of their negative charges.

119. • Proteoglycans: When these chains of
GAGs are attached to a protein, the
compound is known as a proteoglycan,
eg., syndecan, betaglycan, serglycin,
aggrecan, versican, fibromodulin, etc.

120. • With the exception of hyaluronic acid, all
glycosaminoglycans occur in combination
with proteins through covalent bonds
forming proteoglycan. The amount of
carbohydrate in a proteoglycan is usually
much greater than is found in a
glycoprotein and may comprise up to 95%
of its weight.

121. • So proteoglycans are proteins that contain
covalently linked GAGs.
• Proteoglycans vary in tissue distribution,
nature of the core protein, attached
glycosaminoglycans, and function
• The pro­teins bound covalently to
glycosaminoglycans are called "core
proteins"

122. General structure of proteoglycan, aggrecan,
found in cartilage is shown in the following figure
• It is very large (about 2 x 103 kDa), with its
overall structure resembling that of a bottle
brush.
• It contains a long strand of hyaluronic acid
(one type of GAG) to which link proteins are
attached noncovalently.

123. General structure of proteoglycan, aggrecan,
found in cartilage is shown in the following figure
• In turn, link proteins interact
noncovalently with core protein
molecules from which chains of other
GAGs (keratan sulfate and
chondroitin sulfate in this case)
project.

125. •
Attachment of GAGs to core Proteins:
The linkage between GAGs and their
core proteins is generally one of three
types as below

126. • An O‑ glycosidic bond between xylose
(Xyl) and Ser, a bond that is unique to
proteoglycans. This linkage is formed by
transfer of a Xyl residue to Ser from
UDP‑xylose. Two residues of Gal are then
added to the Xyl residue, forming a link
trisaccharide, Gal‑ Gal‑ Xyl‑ Ser. Further
chain growth of the GAG occurs on the
terminal Gal.

127. •
An O‑ glycosidic bond forms between
GalNAc (N‑acetylgalactosamine) and
Ser (Thr) present in keratan sulfate 11.
This bond is formed by donation to Ser
(or Thr) of a GalNAc residue, employing
UDP‑Ga1NAc as its donor.

128. • An N‑ glycosylamine bond between
GlcNAc (N‑acetylglucosamine) and the
amide nitrogen of Asn, as found in
N‑linked glycoproteins.

129. Attachment of GAGs to core Proteins

130. • Synthesis of acidic sugars
• D‑ Glucuronic acid, whose structure is
that of glucose with an oxidized carbon
6 (‑ CH20H  ‑ COOH), and its C‑ 5
epimer, L‑ iduronic acid, are essential
components of glycosaminoglycans.

131. • Glucuronic acid is also required in
detoxification/conjugation reactions of a
number of insoluble compounds, such
as bilirubin, steroids, and several drugs.
• In plants and mammals (other than
guinea pigs and primates, including
man), glucuronic acid serves as a
precursor of ascorbic acid (vitamin C).

132. • Synthesis of acidic sugars
• Glucuronic acid
• Source: Glucuronic acid can be obtained
in small amounts from the diet. It can
also be obtained from the intracellular
lysosomal degradation of
glycosaminoglycans, or via the uronic
acid pathway.

133. • Metabolism: The end‑ product of
glucuronic acid metabolism in humans is
D‑ xylulose 5‑ phosphate, which can enter
the hexose monophosphate pathway and
produce the glycolytic intermediates
glyceraldehyde 3‑ phosphate and
fructose 6‑ phophate .

134. • Active form: The active form of
glucuronic acid that donates the sugar
in glycosaminoglycan synthesis and
other glucuronylating reactions is
UDP‑ gIucuronic acid, which is
produced by oxidation of UDP‑ glucose

135. • Synthesis of acidic sugars
• L‑ Iduronic
• Synthesis of L‑ iduronic acid residues
occurs after D‑ glucuronic acid has
been incorporated into the
carbohydrate chain.
• Uronosyl 5‑ epimerase causes
epimerization of the D‑ to the L‑ sugar.

136. Synthesis of acidic sugars

137. Synthesis of acidic sugars

138. Synthesis of amino sugars

139. • Synthesis of amino sugars
• Amino sugars are essential
components of glycosaminoglycans,
gly­coproteins, glycolipids, and certain
oligosaccharides, and are also found in
some antibiotics.

140. • The synthetic pathway of amino sugars
is very active in connective tissues,
where as much as twenty percent of
glucose flows through this pathway.

141. • Synthesis of amino sugars
• N‑ Acetylglucosamine (glcNAc) and
N‑ acetylgalactosamine (gaINAc):
• The monosaccharide fructose
6‑ phosphate is the precursor of gIuNAc,
gaINAc, and the sialic acids, including
N‑ acetyl­neuraminic acid (NANA, a
nine‑ carbon, acidic monosaccharide).

142. • In each of these sugars, a hydroxyl
group of the precursor is replaced by
an amino group donated by the amino
acid, glutamine.
• The amino groups are almost always
acetylated.

143. • The UDP‑ derivatives of gIuNAc and
gaINAc are the activated forms of the
monosaccharides that can be used to
elongate the carbohydrate chains.

144. • 2. N‑ Acetylneuraminic acid:
N‑ Acetylneuraminic acid (NANA) is a
member of the family of sialic acids, each
of which is acylated at a different site.
These compounds are usually found as
terminal carbohydrate residues of
oligosaccharide side chains of glycopro­
teins, glycolipids, or, less frequently, of
glycosaminoglycans.

145. • The carbons and nitrogens in NANA
come from N‑ acetylman­nosamine and
phosphoenolpyruvate (an intermediate in
the gly­colytic pathway, see p. 100).
[Note: Before NANA can be added to a
growing oligosaccharide, it must be
converted into its active form by reacting
with cytidine triphosphate (CTP).

146. The enzyme N­
acetylneuraminate‑ CMP‑ pyrophosphoryl
ase removes pyrophos­phate from the
CTP and attaches the remaining CMP to
the NANA. This is the only nucleotide
sugar in human metabolism in which the
carrier nucleotide is a monophosphate.]

147. • Synthesis of amino sugars
• 2. N‑ Acetylneuraminic acid:
• N‑ Acetylneuraminic acid (NANA) is a
member of the family of sialic acids,
each of which is acylated at a different
site.

148. • These compounds are usually found as
terminal carbohydrate residues of
oligosaccharide side chains of
glycoproteins, glycolipids, or, less
frequently, of glycosaminoglycans.

149. • The carbons and nitrogens in NANA
come from N‑ acetylmannosamine and
phosphoenolpyruvate (an intermediate in
the glycolytic pathway, see p. 100). [Note:
Before NANA can be added to a growing
oligosaccharide, it must be converted
into its active form by reacting with
cytidine triphosphate (CTP).

150. • The enzyme N­
acetylneuraminate‑ CMP‑ pyrophosphor
ylase removes pyrophosphate from the
CTP and attaches the remaining CMP
to the NANA. This is the only
nucleotide sugar in human metabolism
in which the carrier nucleotide is a
monophosphate.

151. Summary of structures of glycosaminoglycans
and their attachments to core proteins.
Chondroitin sulfate link
Hyluronic acid link
Keratan sulfate link
Heparan sulfate link
Dermatan sulfate link
Heparin link

152. GIcUA, D‑glucuronic acid; IdUA, L‑iduronic
acid;
GIcN,
D‑glucosamine;
D‑galactosamine;
Ac,
acetyl;
GaIN,
Gal,
D‑galactose; Xyl, D‑xy­lose; Ser, L‑serine;
Thr, L‑threonine; Asn, L‑asparagine; Man,
D‑mannose; NeuAc, N‑acetylneuraminic
acid

153. MUCOPOLYSACCHARIDES

154. • 1- Hyluronic acid
• Occurrence: It is present in bacteria and
is widely distributed among various
animals and tissues, including synovial
fluid, the vitreous body of the eye,
cartilage, and loose connective tissues.

155. • As its solution is highly viscous so it
occurs
in
the
joints
of
animas
for
lubrication. In tissues it forms an important
part of the intercellular cement substance
and resists penetration by bacteria.

156. • Effect of enzymes (hyaluronidases):
These enzymes break
hyaluronie acid.
These enzymes are found in certain
bacteria, stings of bees, and snake
venom. In humans these enzymes also
occur in testes, seminal fluid, urine,
plasma, synovial fluid and other tissues.

157. • Enzyme present in
bacteria tends to
destroy the intercellular hyaluronic acid
barrier and permits the invading agent to
penetrate tissues; the enzyme is therefore
also .called the spreading factor.

158. • In humans, the presence of this enzyme in
the seminal fluid is thought to facilitate
fertilization of the ovum.
• The preparations of this enzyme are
clinically used to increase the absorption
of subcutaneously administered fluid.

159. • Some other functions of hyluronic acid
• It is present in high concentration in
embryonic tissues and is thought to play
an important role in permitting cell
migration during morphogenesis and
wound repair.

160. • Its ability to attract water into the extra
cellular matrix and thereby "loosen it up".
• The high concentrations of hyaluronic acid
and chondroitin sulfates present in cartilage
contribute to its compressibility.

161. • Chemically it is a substance of a high
molecular weight and consists of
alternating residues of
N‑ acetylglucosamine and glucuronic
acid.

163. β(14)
β(13)

164. • 2­ Chondroitin sulfates
• Occurrence: In In body these are the
most abundant glycosaminoglycans.
These are found in combination with
protein in the ground substance of tissues
like cartilage and at sites of calcification in
endochondral bone

165. • Types: There are several types of
chondroitin sulfates like A, B, C, and D.
• Structure: These consist of a large number
alternating units of hexosamine (like
N‑acetylgalactosamine) 4‑ (or 6‑) sulfate
and uronic acid ( like glucuronic acid or
iduronic acid). The structure of chondroitin
sulfate D is as follows

166. • Uronic acid may
also be sulfated
• Chondroitin sulfate
B has a weak
anticoagulant
activity, that is why
it is β­heparin
Link
Link

167. 2­ Chondroitin sulfates

168. 3-Heparin
• Structure: The repeating disaccharide
contains glucosamine (GlcN) and either of
the two uronic acids. Most of the amino
groups of the GlcN residues are
N‑sulfated, but a few are acetylated. The
GlcN also carries a C6 sulfate ester.

169. • Occurrence: Heparin is found in the
granules of mast cells and also in liver,
lung, and skin.
• The protein molecule of the heparin
proteoglycan is unique, consisting
exclusively of serine and glycine residues.

172. 3-Heparin

173. • Functions of heparin
• It is an important anticoagulant.
• It binds with factors IX and XI but its most
important interaction is with plasma
antithrombin III. The 1:1 binding of heparin
to this plasma protein greatly accelerates
the ability of the latter to inactivate serine
proteases, particularly thrombin.

174. • The binding of heparin to lysine residues in
antithrombin III appears to induce a
conformational change in this protein that
favors its binding to the serine proteases
like thrombin.
• Heparin can also bind specifically to
lipoprotein lipase present in capillary walls,
causing a release of this enzyme into the
circulation.

175. • 4- Heparan sulfate
• This molecule is present on many cell
surfaces (serving as receptors so it may
participate in the mediation of cell growth
and cell-cell communication) as a
proteoglycan and is extracellular. It contains
GlcN with fewer N‑sulfates than heparin,
and unlike heparin, its predominant uronic
acid is GlcUA.

176. • This proteoglycan is also found in the basement
membrane of the kidney, along with type IV
collagen and laminin, where it plays a major role
in determining the charge selectiveness of
glomerular filtration.

177. • 5- Dermatan sulfate
• This substance is widely distributed in
animal tissues. Its structure is similar to that
of chondroitin sulfate, except that in place of
a GlcUA in β‑1,3 linkage to GaINAC, it
contains an IdUA in an α‑1,3 linkage to
GalNAC.
• Dermatan sulfate contains both IdUAGalNAc and GlcUA‑GaINAc disaccharides

179. • 6,7- Keratan sulfate I and II
• Keratan sulfates consist of repeating
Gal‑GlcNAc disaccharide units containing
sulfate attached to the 6' position of
GlcNAc or occasionally of Gal.

180. • Type I is abundant in cornea, and type II is
found along with chondroitin sulfate
attached to hyaluronic acid in loose
connective tissue. Types I and II have
different attachments to protein as shown
in above structure link.

181. • Functions of kertan sulfate I and
dermatan sulfate
• These are present in the cornea. They lie
between collagen fibrils and play a critical
role in corneal transparency.
• Changes in proteoglycan composition found
in corneal scars disappear when the cornea
heals.

182. • The presence of dermatan sulfate in the
sclera may also play a role in maintaining
the overall shape of the eye.
• Keratan sulfate I is also present in
cartilage.

183. 6,7- Keratan sulfate I and II

184. Major properties of glycosaminoglycans

185. • Functions of heparin
• It is an important anticoagulant.
• It binds with factors IX and XI but its most
important interaction is with plasma
antithrombin III. The 1:1 binding of heparin
to this plasma protein greatly accelerates
the ability of the latter to inactivate serine
proteases, particularly thrombin.

186. • The binding of heparin to lysine residues in
antithrombin III appears to induce a
conformational change in this protein that
favors its binding to the serine proteases like
thrombin.
• Heparin can also bind specifically to
lipoprotein lipase present in capillary walls,
causing a release of this enzyme into the
circulation.

187. • Some clinical considerations
• Enzymes of degradation
– Both exo‑ and endoglycosidases degrade
GAGS, Like most other biomolecules, GAGs
are subject to turnover, being both
synthesized and degraded.

188. • The deficiencies of these enzymes result in
their non‑degradation leading to
accumulation; causing several pathological
conditions that are collectively called
mucopolysaccharidoses. That may involve
cornea, nervous tissues, spleen, liver, joints,
heart valves and coronary arteries,

189. • Arthritis: In various types of arthritis,
proteoglycans may act as autoantigens,
thus contributing to the pathologic features
of these conditions.

190. • Aging: The amount of chondroitin sulfate
in cartilage diminishes with age, whereas
the amounts of keratan sulfate and hyaluronic acid increase. These changes
may contribute to the development of
osteoarthritis.

191. • Changes in the amounts of certain GAGS
in the skin are also observed with age and
help to account for the characteristic
changes noted in this organ in the elderly.

192. • DEGRADATION OF
GLYCOSAMINOGLYCANS
• Glycosaminoglycans are degraded in
lysosomes, which contain hydrolytic
enzymes that are most active at a pH of
approximately 5.

193. • The low pH optimum is a protective
mechanism that prevents the enzymes
from destroying the cell should leakage
occur into the cytosol where the pH is
neutral.

194. • With the exception of keratan sulfate,
which has a half‑ life of greater than 120
days, the glycosaminogly- cans have a
relatively short half‑ life, ranging from
about three days for hyaluronic acid to
ten days for chondroitin and dermatan
sulfate.

195. • DEGRADATION OF
GLYCOSAMINOGLYCANS
• Phagocytosis of extracellular
glycosaminoglycans

196. • Because glycosaminoglycans are
extracellular or cell‑ surface
compounds, they must be engulfed by
an invagination of the cell membrane
(phagocytosis), forming a vesicle
inside of which the
glycosaminoglycans are to be
degraded.

197. • This vesicle then fuses with a
lysosome, forming a single digestive
vesicle in which the
glycosaminoglycans are efficiently
degraded

198. • DEGRADATION OF
GLYCOSAMINOGLYCANS
• Lysosomal degradation of
glycosaminoglycans
• The lysosomal degradation of
glycosaminoglycans requires a large
number of acid hydrolases for complete
digestion.

199. • First, the polysaccharide chains are
cleaved by endoglycosidases,
producing oligosaccharides.

200. • Further degradation of the
oligosaccharides occurs sequentially
from the non‑ reducing end of each
chain, the last group (sulfate or sugar)
added during synthesis being the first
group removed.
• Examples of some of these enzymes and
the bonds they hydrolyze are shown in
the figure on next slide.

201. Synthesis of acidic sugars

202. • The mucopolysaccharidoses
• The mucopolysaccharidoses are
hereditary disorders that are clinically
progressive. They are characterized by
accumulation of glycosaminoglycans in
various tissues, causing varied
symptoms, such as skeletal and
extracellular matrix deformities, and
mental retardation.

203. • Mucopolysaccharidoses are caused by
a deficiency of one of the lysosomal
hydrolases normally involved in the
degradation of heparan sulfate and/or
dermatan sulfate (shown in figure on
previous slide).

204. • This results in the presence of
oligosaccharides in the urine, because
of incomplete lysosomal degradation of
glycosaminoglycans.

205. • These fragments can be used to
diagnose the specific
mucopolysaccharidosis, namely by
identifying the structure present on the
nonreducing end of the
oligosaccharide.

206. • The mucopolysaccharidoses
• That residue would have been the
substrate for the missing enzyme.
• Diagnosis is confirmed by measuring
the patient's cellular level of lysosomal
hydrolases.

207. • Children who are homozygous for one of
these diseases are apparently normal at
birth, then gradually deteriorate.
• In severe cases, death occurs in
childhood.
• All of the deficiencies are autosomal and
recessively inherited except Hunter
syndrome, which is X‑ linked.

208. • Bone marrow transplants are currently
being used successfully to treat Hunter
syndrome; the transplanted
macrophages produce the sulfatase
needed to degrade
glycosaminoglycans in the
extracellular space.

209. • The mucopolysaccharidoses
• Some of the lysosomal enzymes
required for the degradation of
glycosaminoglycans also participate in
the degradation of glycolipids and
glycoproteins.

210. Hunter Syndrome
• Induronate sulphatase deficiency
• X-linked
• Wide range of severity.
• No corneal clouding but physical deformity
• Mental retardation is mild to severe
• Degradation of Heparan Sulphate and dermatan
sulphate is affected.

211. Hurler’s Syndrome
• Alpha-L-Iduronidase deficiency
• Corneal clouding, mental retardation dwarfing, upper
Airway obstruction
• Coronary artery deposition leads to ischemia and early
death
• Degradation of Heparan sulphate and Dermatan
Sulphate is effected.
• Can be treated by Bone Marrow transplant before 18
months of life

212. San Fi Lippo Syndrome (MPS-III)
Types – A, B, C, D
• Four enzymatic steps are necessary to remove
N-sulphated and N-acetylated glucosamine
residues from Heparan Sulphate

213. Type A: Heparan Sulfamidase deficiency
Type B: N-Acetyl glucosulphatase deficiency
Type C: Glucosamine-N-Acetyl transferase deficiency.
Type D: N-Acetyl glucosamine-6-sulphatase deficiency.
Severe nervous system disorders. Mental
retardation

214. SLY Syndrome MPS VII
• Beta-Glucuronidase deficiency
• Hepatomegaly, splenomegaly, skeletal
deformity, short stature, corneal clouding,
mental deficiency
• Degradation of dermatan sulphate and
Heparan sulphate are affected

215. • Therefore, an individual suffering from
a specific mucopolysaccharidosis may
also have a lipidosis or
glycoprotein‑ oligosaccharidosis.]

216. Summary of functions of
glycosaminoglaycans
HA, hyaluronic acid; CS, chondroitin sulfate;
KS I, keratan sulfate I; DS, dermatan
sulfate; HS, heparan sulfate.

217. • Act as structural components of the
extracellular (EC) matrix
• Have specific interactions with collagen,
elastin, fibronectin, laminin, and other
proteins such as growth factors
• As polyanions, bind polycations and cations
• Contribute to the characteristic turgor of
various tissues

218. • Act as sieves in the EC matrix
• Facilitate cell migration (HA)
• Have role in compressibility of cartilage in
weight‑bearing (HA, CS)
• Play role in corneal transparency (KS I and
DS)
• Have structural role in sclera (DS)

219. • Act as anticoagulant (heparin)
• Are components of plasma membranes,
where they may act as receptors and
participate in cell adhesion and cell-cell
interactions (eg, HS)

220. • Determine charge‑selectiveness of renal
glomerulus (HS)
• Are components of synaptic and other
vesicles (eg, HS)

221. Peptidoglycan
Forms the cell walls of bacteria.
A complex polysaccharide of alternating Nacetylglucosamine (or NAG) and Nacetylmuramiic acid (or NAM) connected
by β(1→4) glycosidic bonds with short
peptides bridging the polysaccharide
chains.

222. Peptidoglycan

223. • Peptidoglycan froms the cell wall of
bacteria, capsular antigens, microbial
toxins, and procoagulant substances
produced by microbial pathogens may all
contribute to the pathogenesis of sepsis.

224. • It has been observed that peptidoglycan,
like teichoic acid and other components of
gram-positive bacteria, may interact with
CD14 molecules and activate
inflammatory cells in a manner similar to
that of bacterial endotoxin.

225. • The wall protects bacterial cells from
osmotic rupture, which would result from
the cell's usual marked hyperosmolarity (by
up to 20 atm) relative to the host
environment.
• The structure conferring cell-wall rigidity
and resistance to osmotic lysis in both
gram-positive and -negative bacteria is

226. • Peptidoglycan.
• Chemotherapeutic agents directed at any
stage of the synthesis, export, assembly,
or cross-linking of peptidoglycan lead to
inhibition of bacterial cell growth and, in
most cases, to cell death.

227. •
Peptidoglycan is composed of
•
a backbone of two alternating sugars, Nacetylglucosamine and N-acetylmuramic
acid;
•
a chain of four amino acids that extends
down from the backbone (stem peptides);
and
•
a peptide bridge that cross-links the
peptide chains.