Going into the molecules that form the basis of life!

1. Heteropolysaccharides:
Glycosaminoglycans and Glycoconjugates

2. Name: Marryam Faiz
Roll. No: Z18-15

3. My Panel
Areej Ahmad Siddiqua Javed
Sarim Hassan
Roll. No.
Z19-24
Roll. No.
Z19-01
Roll. No.
Z19-03

4. Contents
 Polysaccharides
 Classification
 Glycosaminoglycans
 Structure
 Examples
 Mucopolysaccharidoses
 Glycoconjugates
 Types
 Glycoproteins
 Glycolipids
 Proteoglycans
 Examples
 Significance

5. Polysaccharides
• They are a long polymeric chain of
monosaccharide units bound together
by glycosidic bonds.
• These are the most
abundant carbohydrates found in food.
Homoglycans:
• contain one
monosaccharide
unit.
• e.g. starch,
cellulose,
glycogen
Heteroglycans:
• contain two or
more
monosaccharide
units.
• e.g.
GAGs, agar,
peptidoglycans

6. Polysaccharide
Heteroglycan
Hyalrunan Heparin Dermatan
Homoglycan
Cellulose Starch Glycogen

7. Heteroglycans
(heteropolysaccharides)
Most naturally occurring heteroglycans contain only 2 different
monosaccharides and are closely associated with lipid or protein.
The major heteropolysaccharides include
• the connective-tissue polysaccharides
• the blood group substances
• glycoproteins (combinations of carbohydrates and proteins) such
as gamma globulin,
• glycolipids (combinations of carbohydrates and lipids)

8. Glycosaminoglycans
(GAG)

9. What Is Glycosaminoglycan (GAG)?
• Heteropolysaccharides of the ECM/ground substance.
• Formerly known as mucopolysaccharides.
• A type of linear polymer made up of repeating disaccharide units (two-
sugar units).
• The repeating two-sugar unit consists of a uronic sugar and an amino
sugar (with a few exceptions).

10. Properties
• Highly negatively charged.
• Highly polar and attract water.
• GAGs are hydrophilic molecules capable of absorbing up to 1000 times their
volume in water to form gel-like materials.
Ocurrence
• Only present in animals and bacteria and not in plants.

11. Glycosaminoglycans
(GAG)

12. Composition
Amino sugar:
• It comprises of
N-Acetylglucosamine or
N-acetylgalactosamine
Uronic (acidic)
sugar:
• It is made up of
D-glucuronic or
Liduronic acid or
Galactose.

13. Examples

14. Hyaluronate
• Only GAG that is non-sulphonated.
• Composed of D-glucuronic acid and N-
acetyl-D-glucosamine.
• Can be 25,000 disaccharide repeats in
length.
• Highly viscous
• Lubricant and shock absorber
• Hyaluronidase hydrolyses it and reduces
viscosity (spleen and testicular tissues).
• Occurrence : synovial fluid, ECM of
loose connective tissue, vitreous humor of
eye

15. Hyaluronidase
• Hyaluronidase is an enzyme.
• It hydrolyses HA and reduces viscosity.
• It is present in the spleen and testicular
tissues.
• The enzyme is also secreted by some
bacteria.
• It hydrolyzes the glycosidic linkages of
hyaluronan.
• Thus tissues are more susceptible to
bacterial invasion.

16. Chondroitin Sulphate
 A
sulfated glycosaminoglycan (GAG).
 Composed N-acetylgalactosamine
(GalNAc) and glucuronic acid
(GlcA)
 Most abundant GAG in the body
 Found in cartilage, ligaments,
tendons and aorta
 Of 2 types, A and B.
 Binds collagen in cartilage to form a
strong network.
 A widely used dietary
supplement for treatment
of osteoarthritis.

17. Dermatan Sulphate
 Composed of N-acetyl
galactosamine (GalNAc) and iduronic
acid (IdoA).
 Greek ‘derma’ is ‘skin.’
 Contains small amounts of other
carbohydrates.
 It is also referred to as chondroitin sulfate
B, although it is no longer classified as a
form of chondroitin sulfate by most sources.
 Found mostly in skin, but also in blood
vessels, heart valves

18. Keratan Sulphate
• Composed of N-acetyl-
glucosamine-6-phosphate and D-
galactose.
• Most common heterogenous GAG.
• Greek ‘keras’ is ‘horn’.
• Form dead cells like horn, hair nails
and claws.
• Found especially in
the cornea, cartilage, and bone.
• Act as a cushion to
absorb mechanical shock.

19. Heparin
• Isolated from dog liver cells (hepar is Greek
for "liver"; hepar +in).
• Composed of a glucuronic acid (GlcA) linked
to N-acetylglucosamine (GlcNAc), typically
making up around 50% of the total
disaccharide units
• Serves as an anti-coagulant
• Heparans have less sulfate groups than
heparins.
Occurence :
•Heparin :arteries of the lungs, liver and skin
•Heparan sulfate : basement membranes,
component of cell surfaces

20. Representative heteropolysaccharides
*Covalently linked to protein; the proportion of protein to carbohydrate in such complex molecules
varies from about 10% protein in the case of chondroitin-4-sulfate to better than 95% for gamma
globulin.
heteropolysaccharide component sugars functions distribution
hyaluronic acid
D-glucuronic acid and N-
acetyl-D-glucosamine
lubricant, shock
absorber, water binding
connective tissue, skin
chondroitin-4-sulfate*
D-glucuronic acid and N-
acetyl-D-galactosamine-
4-O-sulfate
calcium accumulation,
cartilage and bone
formation
cartilage
heparin*
D-glucuronic acid, L-
iduronic acid, N-sulfo-D-
glucosamine
anticoagulant mast cells, blood
gamma globulin*
N-acetyl-hexosamine, D-
mannose, D-galactose
antibody blood
blood group substance*
D-glucosamine, D-
galactosamine, L-fucose,
D-galactose
blood group specificity
cell surfaces, especially
red blood cells

21. Glycoconjugates

22. Mucopolysaccharidosis
 A group of metabolic disorders caused by the
absence or malfunctioning of the 11
lysosomal enzymes needed to break down
GAGs.
 Over time, these GAGs collect in the cells, blood
and connective tissues.
 This accumulation affects appearance, physical
abilities, organ and system functioning.
 1 in 25,000 babies born will have some form of
the mucopolysaccharidoses.

23. Symptoms
 Intellectual disability
 Corneal clouding
 Developmental delay
 Retinal degradation
 Macroglossia (unusually enlarged tongue)
 Coarse facial features
 Hepatosplenomegaly (enlargement of both liver and spleen)

24. Function

25. Glycoconjugates

26. Glycoconjugates
 Classification family
of carbohydrates – referred to
as glycans.
 Covalentlylinked with proteins, pep
tides, lipid, and other compounds.
 Although the important molecular
species DNA, RNA, ATP, all contain
a carbohydrate part, generally they
are not considered as
glycoconjugates.
 In 2021 glycoRNAs were observed
for the first time.

27. Significance
Glycoconjugates
1
2
3
4
Cell to cell
recognition
Cell to matrix
interaction
Detoxification
Long term
immunity
response

28. Glycoconjugates
There are various types:
1. Glycoproteins
2. Glycolipids
3. Glycopeptides
4. Glycosides
5. Peptidoglycans
6. Proteoglycans
Types

29. Glycoproteins
 Glycoproteins are proteins containing
glycans covalently attached to amino acid
side chains.
 The carbohydrate may constitute from 1-
70 % of mass.
 The carbohydrate is attached to the
protein in a posttranslational modification
process known as glycosylation.
 Within the cell, they appear in/on the:
1. blood
2. extracellular matrix
3. outer surface of the plasma membrane

30. Glycosylation
 The carbohydrate constituent is attached to the protein via
1. the -OH group of serine or threonine (i.e. O-glycosylation) or
2. the amide NH2 of asparagine (i.e. N-glycosylation).

31. vg
Examples
•Collagen
•Mucins
•Secretions
•Immunoglobulins
•Lectins
•Surface membrane glycoproteins
•Milk proteins
•Proteins secreted by pancreas

32. Glycoproteins and Corona virus
 COVID-19 has surface glycoproteins called
spike domains; S (Latin ‘crown-
like’=‘corona’), which enable it to bind to
their target receptors.
 The S domain is the main site for antibodies to
neutralize the viruses. Hence it is targeted for
successful vaccination.
 The S domains (corona and influenza) are
constantly changing (mutating), hence the
seasonal epidemics, despite previous
antibodies.
 COVID-19 has now mutated into many
different variants. This has caused concern over
the possibility of altering transmission or the
effectiveness of vaccines.

33. Glycolipids
 A carbohydrate, usually an
oligosaccharide, that is covalently linked
to a lipid molecule.
 Found on the extracellular face of
eukaryotic cellular membranes.
 Can act as receptors for viruses and
other pathogens to enter cells.
 The brain and neurons are rich in
glycolipids.

34. Function
 Maintain stability of the membrane
 Facilitate cell–cell interactions
 Help in nerve conduction and
myelin formation
 Play role in signal transduction

35. ABO Blood Group
System
 Specific glycoproteins (and glycolipids) present on
the surface of red blood cells determine blood group
type.
 A-oligosaccharide for A group
 B-oligosaccharide for B group
 Both A & B oligosaccharides for AB group, and
 Absence of both A & B for O
After ABO determination,
 Presence of Rh factor (an antigen) determines
Rh+ groups
 Whereas the absence of the Rh antigen leads to Rh-
groups

36. Proteoglycans
 Proteoglycans are proteins that are
heavily glycosylated.
 The GAGs extend perpendicular from the
core protein in a bottlebrush- like
structure.
 They act as polysaccharides rather than
proteins as 95% of their weight is
composed of GAG’s.
 Mammalian cells can produce 40 types of
proteoglycans.

37. Structure
 The basic structure consists of a
covalently linked
1. Core protein with
2. GAG/s
 The point of attachment is a serine
residue.
 The GAGs extend perpendicular from
the core protein in a bottlebrush- like
structure.
 The GAG is joined to Ser via the
tetrasaccharide bridge.
 The Ser residue is generally in the
sequence -Ser-Gly-X-Gly.

38. 1. Core Protein
 The basal lamina limits contact between epithelial cells and other groups.
 It contains a family of core proteins (Mr 20000-40000).
 Each protein is with several covalently attached heparan sulphate.
 2 major families of membrane heparan sulphate proteoglycans.
Syndecans:
 have a single transmembrane domain
and an extracellular domain
 The extracellular domain has 3-5
chains of HS and sometimes
chondroitin sulphate.
Glypicans:
 Only an extracellular domain
 Attached to membrane by a lipid
anchor.

39. 2. GAG Chain
 These can bind to extracellular
ligands.
 Some domains (3-8
disaccharide units long) differ
from neighbouring domains in
sequence and binding ability.
 Highly sulphated domains (NS)
alternate with domains having
unmodified GlcNAc and GlcA
residues.
 The exact pattern of sufation in
NS domain depends om the
particular proteoglycan.

40. Summary
 Heteropolysaccharides: contain two or more monosaccharide units e.g. GAGs, agar,
peptidoglycans
 Glycosaminoglycans: Heteropolysaccharides of the ECM/ground substance.
 Structure: repeating two-sugar unit consists of a uronic sugar and an amino sugar
 Examples: hyaluronate, keratan sulphate, heparin, chondroitin suphate
 Mucopolysaccharidoses: group of metabolic disorders caused by the absence or
malfunctioning of the 11 lysosomal enzymes needed to break down GAGs.
 Glycoconjugates: classification family for carbohydrates.
 Types
 Glycoproteins: proteins containing glycans covalently attached to amino acid
side chains.
 Glycolipids: A carbohydrate, usually an oligosaccharide, that is covalently
linked to a lipid molecule.
 Proteoglycans: Proteoglycans are proteins that are heavily glycosylated.
 Significance

41. ANY
QUESTIONS?

42. THANK YOU