This document discusses heteropolysaccharides, also known as heteroglycans or glycosaminoglycans (GAGs). GAGs are polymers made from more than one type of monosaccharide or monosaccharide derivative. Examples include those found in plants like agar and pectin, and those found in humans like hyaluronic acid, chondroitin sulfate, and heparin. The document describes the composition, location, and functions of several major GAGs, including their roles in structures like the extracellular matrix, cartilage, and blood groups. Proteoglycans are also discussed, which are core proteins that have one or more GAG chains covalently attached.
3. Heteropolysaccharides
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2 or more different monosaccharide units or their derivatives
Plant Heteroglycans
Agar
Gum
Pectin
Human Glycosaminoglycans
Hyaluronic acid
Chondritin sulfate
Heparin
Dermatan sulphate
Keratan sulphate
Unbranched – contains two types of subunits
Branched – contains more than two types of monosaccharide subunit
4. Agar
Contains repeat units of sulphated galactose , glucose & other sugars.
Obtained from sea weeds
It is dissolved in water at 100 o C , which upon cooling sets into a gel
Functions :
Cannot be digested by bacteria. So used as supporting agent to culture bacterial
colonies.
Also as support medium of immuno diffusion & immuno-electrophoresis.
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5. Agarose
galactose and 3,6 anhydrous galactose units
Used as matrix for electrophoresis.
Pectins
contains glucose and uronic acid residues
Used as dietary fiber
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6. Glycosaminoglycans / GAGs or Mucopolysaccharides
GAGs are ground substance in connective tissues
Mucus membrane are covered by these polysaccharide containing proteoglycans.
GAGs extend perpendicularly from the core protein in a brush like structure.
Present almost everywhere in our body
Perform highly diverse functions -Provides protection, Shape , Extracellular support
to Cells, tissues & organs from bacteria to different tissues.
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7. Glycosaminoglycans / GAGs or Mucopolysaccharides
Long, Unbranched heteropolysaccharide, made of repeating disaccharide units
containing uronic acid & amino sugars.
Amino sugar – D-Glucosamine or D-Galactosamine
(Present in there acetylated form, sulfate and carboxyl groups
may be present also )
Uronic acid – D-Glucuronic acid or L-Iduronic acid
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--- [ URONIC ACID + AMINO SUGAR]---n
8. GAGs are the most important group of heteroglycan in humans.
First isolated from mucin so called mucopolysaccharides.
Major components of extracellular matrix of connective tissue, including bone
and cartilage, synovial fluid, vitreous humor and secretions of mucus producing
cells.
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9. Relationship between structure and function of GAGs
Gel forming component of extracellular matrix
The anionic groups (carboxy & sulfate groups) being strongly hydrophilic tend
to bind large amount of water producing gel like matrix, that forms the bodies
ground substance.
Heteropolysaccharide chains repel one another and therefore exist in
extended conformation in solutions.
This produces slippery consistency of mucus secretions and synovial fluid.
10. The negative charge serves two purpose :
In the glomerular basement membrane, heparin sulfate’s negative charge is
responsible for the selectivity of the basement membrane which prevents the
albumin from being excreted through the pores.
The negative charge attracts positively charged sodium ions which will
Osmotically drag water. They hold excess water and gives the gel like elastic
consistency of the extracellular matrix.
11. Resilience of GAG
Large number of -ve charge
GAG are extended in solution
Repel each other
Surrounded by shell of water molecules
12. Structural support to connective tissue
GAGs form matrix or ground substance that stabilizes and supports the cellular
and fibrous components of tissues.
Other functions :
Plays an important role in mediating cell-cell interactions
Their slippery consistency makes them suitable for a lubricant action in joints.
14. To describe MPS or GAG
Name of Repeating
disaccharide unit
- Sulphated or not
-Name of Uronic acid
– Name of Amino sugar
Location/sites of availability
in human body
Functions
15. 15
Thumb rule for GAG’s
All GAG’s are extra cellular except Heparin which is intracellular.
All GAG’s are sulphated except Hyaluronic acid.
All GAGs attached to core protein except hyaluronic acid
GAGs are linked by O linkage except KS type I-N linkage
All GAG’s contain uronic acid except Keratan sulphate which contains Galactose.
Iduronic acid - Heparan and Dermatan sulphate
NAG - Glucuronic acid – NAG is attached by β1 3, β14 linkage EXCEPT Heparin,HS - α14 linkages
,dermatan sulfate - β1 3.
All have short ½ life except Keratan sulphate – 120 days.
16. Hyaluronic acid
• N-acetyl glucosamine - Glucuronic acid linked by β 1,3 , β1,4 linkage
Disaccharide unit
• Synovial fluid, vitreous humour, connective tissues and tendon.
Location
• Serve as lubricant and shock absorber
Function
17. Hyaluronic acid
It is sulfate free GAG and not attached to core protein.
Jelly like substance, an important and major component of ground substance of
connective tissue and cartilage.
Synovial fluid of joints, vitreous humor of eye, loose connective tissues and
cartilage.
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β 1-3 β 1-4
18. 18
Functions of Hyaluronic acid
Serves as a lubricant and shock absorbant in joints.
Acts as seives in extracellular matrix.
Permits cell migration during morphogenesis & wound repair.
19. 19
Hyaluronidase is an enzyme that breaks β1 – 4 linkages of hyaluronic acid.
Present in high concentration in seminal fluid, & in certain snake and insect
venoms.
Hyaluronidase enzyme of semen degrades the gel around ovum & allows
effective penetration of sperm into ovum, thus helps in fertilization.
The invasive power of some pathogenic organism may be increased because they
secrete hyaluronidase.
20. 20
Osteoarthritis :
most common form of arthritis
progressive degeneration of cartilage glycosaminoglycans (GAGs).
Cause – Nutritional deficiency or (most commonly) due to the overuse of
weight-bearing joints (knees).
Commercial preparations of glucosamine sulfate & chondroitin sulfate are
prescribed routinely to the patients with osteoarthritis.
They are called neutraceuticals – drugs like effect.
Glucosamine stimulate the synthesis of cartilage components as well as
promote the incorporation of sulfur into cartilage and, hence, it also helps in
joint repair.
21. 21
• Most abundant GAG in body.
•2 types of chondroitin sulfate : Sulphated at C 4 or C 6 group.
Chondroitin sulfate
β 1-3
β 1-4
22. Chondroitin sulfate
• N-acetyl galactosamine-Glucuronic acid
Disaccharide unit
• At sites of calcification in bone , tendon and cartilage
Location
• Provide an endoskeletal structure
Function
23. 23
Widely distributed in bone, cartilage, ligaments, tendons
& aorta.
Functions :
In cartilage, it binds collagen & hold fibers in a tight strong
network.
It contributes to the compressibility and weight bearing
capacity.
25. Present in skin, blood vessels, cardiac valves & tendon.
Function :
Present in sclera of eye where it has important function in maintaining
overall shape of eye.
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26. Dermatan sulphate
• Glatacosamine-L -iduronic acid
Disaccharide unit
• Skin, blood vessels, cardiac valves & tendon
Location
• Maintains overall shape of eye.
Function
27. Heparin
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• only GAG present intracellular : in granules of mast cells that line the arteries,
especially in lungs, liver and skin.
α 1,4
L-Iduronate
28. Heparin
• Glucosamine-L -iduronic acid
Disaccharide unit
• Intracellular component of mast cell
Location
• Serves as an anticoagulant
Function
29. 29
Strongly acidic due to presence of more sulfate group. (An average of 2.5 sulphate
groups per disaccharide unit is seen)
Functions :
It is an anticoagulant (prevents blood clotting ) It binds with factors IX and XI, but
its most important interaction is with plasma antithrombin III.
Heparin helps in the release of the enzyme lipoprotein lipase (LPL) which helps to
clear the lipidemia after fatty meal – so called clearing factor.
30. 30
Heparan sulfate
Structurally similar to heparin, but has a:
Lower molecular weight
contains higher acetyl groups & less sulfate group
Predominant uronic acid is D-Glucuronic acid
It is an extracellular GAG found in basement membrane and is an essential component of cell
surfaces.
Functions -
Determines charge selectiveness of renal glomerulus.
Involved in cell differentiation, cell growth, cell-cell communication.
31. Keratan sulfate
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•Only GAG with no uronic acid.
•Most heterogenous – contains L-fucose, N-acetyl neuraminic acid and mannose.
32. Keratan sulfate
• N-acetyl glucosamine - Galactose
Disaccharide unit
• Cornea, loose connective tissue, cartilage
Location
• Transparency of cornea
• Acts as a cushion to absorb mechanical shock
• Also synthesis in CNS – development & glial scar formation following an injury
Function
33. KS I - Found in cornea
KS II – Found in loose connective tissue proteoglycan
aggregates with chondroitin sulfate.
Function :
Maintains the corneal transparency.
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36. Blood group substances (blood gr Antigens)
RBC membrane contains several antigenic substance, based on which person
are classified into different blood groups.
They contain carbohydrates as glycoproteins or glycolipids.
N-Acetylgalactosamine, galactose, fucose, sialic acid etc are found in blood gr
substances.
Carbohydrate content plays a determinant role in blood grouping, hence play a
role in identification of blood groups.
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37. 37
Is associated with 3 blood gr substances on RBC s designated as A,B & H antigen.
H antigen :
is basic structure, is characteristic of type O and is present on all blood types.
Fucose – Gal – Gal NAc – Protein .
A antigen : Fucose – Gal – GalNAc – Protein
|
GalNAc
B antigen : Fucose – Gal –GalNAc – Protein
|
Gal
blood group determining sugar – FUCOSE – 6 deoxy galactose
ABO system
38. Type AB has all three of these antigen
Ag which are not present in an individual blood will cause ab to be produced, which
will bind to the foreign glycolipids.
For this reason, people with blood type AB can receive transfusion from all blood
type AB can receive transfusion from all blood types (the universal acceptors), and
people with blood type O can act as donors to all blood types (the universal donor)
39. Some Functions of Glycosaminoglycans and Proteoglycans
Act as structural components of the ECM
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
Act as sieves in the ECM
Facilitate cell migration (HA)
40. Functions of Glycosaminoglycans and Proteoglycans contd..
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)
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)
Determine charge-selectiveness of renal glomerulus (HS)
Are components of synaptic and other vesicles (eg, HS)
41. GAGs Composition Location Functions
Hyaluronic acid
Hyaluronidase is an enzyme
that breaks β-1 – 4 linkages.
N-acetyl glucosamine -
Glucuronic acid
Synovial fluid, vitreous
humour, connective tissues
and tendon.
Present in high concentration
in seminal fluid, & in certain
snake and insect venoms.
Serve as lubricant and shock
absorber. Determines charge
selectiveness of renal
glomerulus.
Acts as seives in extracelluar
matrix.
Hyaluronidase enzyme of
semen degrades the gel
around ovum & allows
effective penetration of sperm
into ovum.
Condroitin sulfate-
Sulphated at C 4 or C 6
group.
N-acetyl galactosamine-
Glucuronic acid
At sites of calcification in bone
, tendon and cartilage
Provide an endoskeletal
structure
Dermatan sulfate L-iduronic acid and N-acetyl
galactosamine 4 sulfate.
Present in skin, cardiac valves
& tendon, sclera of eye
function in maintaining overall
shape of eye.
Keratan sulfate N-acetyl glucosamine -
Galactose
Cornea, loose connective
tissue, cartilage
Transparency of cornea
42. GAGs Composition Location Functions
Heparin Glucosamine 6 sulphate -
L -iduronic acid
Intracellular component of
mast cell
Natural anticoagulant
Heparan sulphate (HS) Similar to heparin, except that
some of glucosamine units are
acetylated and have fewer
sulphated groups
Cell membrane Receptor, cell growth, cell –
cell communication
Blood group antigen Galactose, glucose , fucose,
N-Acetyl galactosamine, N-
Acetyl glucosamine attached to
protein and lipid on the surface
of RBC
Bloog group ag are surface
markers on the red blood cell
membrane
Identification of blood groups
45. Proteoglycans
Proteoglycans are proteins that contain covalently linked glycosaminoglycans.
E.g. Syndecan,betaglycan, serglycin, perlecan, aggrecan, versican,decorin, biglycan, and
fibromodulin.
They vary in tissue distribution, nature of the core protein and glycosaminoglycans
attached, and function.
The proteins bound covalently to glycosaminoglycans are called “core proteins”
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.
46. The linkage between GAGs and their core proteins is generally one of three types.
1)An O-glycosidic bond between xylose (Xyl) and Ser, a bond that is unique to proteoglycans.
2)An O-glycosidic bond forms between GalNAc (N -acetylgalactosamine) and Ser (Thr)
present in keratan sulfate II.
3)An N-glycosylamine bond between GlcNAc (N- acetylglucosamine) and the amide
nitrogen of Asn, as found in N-linked glycoproteins.
The synthesis of the core proteins occurs in the endoplasmic reticulum, and formation of at
least some of the above linkages also occurs there. Most of the later steps in the biosynthesis
of GAG chains and their subsequent modifications occur in the Golgi apparatus.
47. Two families of membrane proteoglycans
Mammalian cells have
at least 30 types
of proteoglycans.
Basic unit: a core protein
with covalently attached
glycosaminoglycan(s).
Heparan sulfate bind a variety of extracellular
ligands and thereby modulate the ligands interaction with
specific receptors of the cell surface
48. Schematic representation of the proteoglycan -Aggrecan
Association b/w HA & core
protein is non covalent but
ionic interaction stabilized by
link protein
Core proteins are covalently attached to GAGs
50. Glycoproteins
Glycoproteins have one or several oligosaccharides of varying complexity joined covalently to
a protein.
They are found on the outer face of the plasma membrane, in the extracellular matrix, and in
the blood.
Inside cells they are found in specific organelles such as Golgi complexes, secretory granules,
and lysosomes.
The oligosaccharide portions of glycoproteins are less monotonous than the glycosaminoglycan
chains of proteoglycans.
They are rich in information, forming highly specific sites for recognition of signals and high-
affinity binding by other proteins by cell receptors.
51. There are 3 major classes of glycoproteins
1. those containing an O-glycosidic linkage (ie,O-linked), involving the hydroxyl side
chain of serine/ threonine or hydroxylysine & hydroxyproline and a sugar such
as N-acetyl galactosamine or or galactose or xylose (GalNAc-Ser[Thr])
2. those containing an N-glycosidic linkage (ie, N-linked), involving the amide
nitrogen of asparagine or lysine and N-acetyl glucosamine (GlcNAc- Asn)
3. Glycosylphosphatidylinositol-anchored glycoprotein (GPI-anchored, or GPI
linked). C terminal a.a is linked to carbohydrate man-man-man glucosamine
through ethanolamine and is again linked to the outer leaflet of plasma
membrane through inositol.
Defect in GPI –anchor synthesis leads to PNH paroxysmal nocturnal hemoglobinuria , HPMRS
hyperphosphatasia with mental retardation syndrome
52. Carbohydrates found in glycoproteins
Hexoses Mannose , Galactose , Glucose
Acetyl hexoseamines N –acetyl glucosamine
N – acetyl galactoamine
Pentoses Arabinose ,
Xylose
Methyl pentose (deoxysugars) L – fucose, L-rhamnose
Sialic acid N – acetyl derivative of
neuraminic acid
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54. 54
Angiotensin converting enzyme 2 (ACE-2) is a glycoprotein with 805
aminoacids. It acts as a receptor for the spike protein S1 of SARS-CoV-2
(Covid -19) viral entry into cell.
55. Proteoglycan Glycoprotein
GAGs are covalently attached to
a protein (95 % sugar)
Primarily of protein with small
amount of carbohydrates
Sugar chain are longer (100 or
more sugars)
Short oligosaccharide chain
(>20)
Linear , unbranched Highly Branched
Disaccharide repeats Do not have repeat sequence
56. Glycolipids
Lipids with carbohydrates attached by a glycosidic bond
Role is to maintain stability of cell membrane and to facilitate cellular
recognition – plays a role in immune response and in cell-cell connection to
form tissues.
They are found in all eukaryotic cell membrane – where they extend from
PL bilayer into EC environment.
Essential feature of glycolipid – presence of monosaccharide /
oligosaccharide bound to lipid moiety.
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Editor's Notes
Nitrogenous hetero
Non nitro – no sugar amines
Chondroitin-4-sulfate (Greek: chondros, cartilage), a
major component of cartilage and other connective tissue, has N-acetyl-D-galactosamine-4-sulfate residues in place of
hyaluronate’s N-acetyl-D-glucosamine residues.
Heparin is a variably sulfated GAG that consists predominantly of alternating (1 S 4)-linked residues of Liduronate-2-sulfate and N-sulfo-D-glucosamine-6-sulfate.
It has an average of 2.5 sulfate residues per disaccharide unit, which makes it the most negatively charged polyelectrolyte
in mammalian tissues (Fig. 11-23). Heparin, in contrast to the above GAGs, is not a constituent of connective tissue, but occurs almost exclusively in the intracellular
granules of the mast cells that line arterial walls, especially
in the liver, lungs, and skin. It inhibits the clotting of blood,
and its release, through injury, is thought to prevent runaway
clot formation (Section 35-1Ea). Heparin is therefore
in wide clinical use to inhibit blood clotting, for example, in
Keratan sulfate (Greek: keras, horn; not to be confused
with the protein keratin) consists mainly of alternating
(1 S4)-linked D-galactose and N-acetyl-D-glucosamine-6-
sulfate residues (and hence lacks uronic acid residues). It is
a component of cartilage, bone, cornea, as well as hair,
nails, and horn. Keratan sulfate is the most heterogeneous
of the major GAGs in that its sulfate content is
variable and it contains small amounts of fucose, mannose,
N-acetylglucosamine, and sialic acid.
Type of oligosaccharide present on surface of RBC determine a persons blood type.