Glycosaminoglycans

■POLYSACCHARIDES – Most of the carbohydrates found in

nature occur in the form of high molecular polymers called
polysaccharidesPolysaccharides are of two types :
a) Homopolysaccharides
b)Heteropolysaccharides
■HOMOPOLYSACCHARIDES – polymer of same
monosaccharide units eg : Starch, Glycogen, Inulin, Cellulose,
Pectin, Chitin.
■HETEROPOLYSACCHARIDES – polymer of different
monosaccharide units eg : Mucopolysaccharides
■ Heteropolysaccharides are High-molecular weight
carbohydrate polymers more than one kind of
monosaccharide.

■ Chemically, they are formed mostly of repeated

disaccharides units that contain amino sugar (N- acetyl
glucosamine or N-acetyl galactosamine), uronic acid
(glucuronic acid or its 5 epimer iduronic acid).
 Glycosaminoglycans
■ Glycosaminoglycans (GAGs) or mucopolysaccharides are long unbranched
polysaccharides consisting of a repeating disaccharide unit.

■ GAGs-High-Molecular-weight carbohydrate polymers.

Glycosaminoglycans forming the proteoglycans are the
most abundant heteropolysaccharides in the body.

■ They are long unbranched molecules containing a repeating

disaccharides unit. One or both sugars contain Sulfate
Groups (the only exception is Hyaluronic acid).
 Functions
■ They have the special ability to bind large amounts of water,
there by producing the gel-like matrix thatt forms the basis of
the body’s ground substance.

■ Since they are negatively charged, for example, in bone,

glycosaminoglycans attract and tightly bind cations like ca++,
they also take-up Na+ and K+.

■ GAGs stabilize and support cellular and fibrous components of

tissue while helping maintain the water and salt balance of the
body.
■ Its essential components of the extra cellular matrix, GAGs play an
important role in mediating cell-cell interactions.

■ Ground substance is a part of connective tissue, which is a gel like

substance containing water, salt, proteins and polysaccharides.

■ An example of specialized ground substance is the synovial fluid, which serves

asa lubricant injointss,and tendon sheaths.
 Types
■ GAGs are either sulfate groupfreeor sulfate group containing

■GAGs are sulfate group free(Hyaluronic acid)

■GAGs are sulfate group containing as

 Chondroitin sulfate
 Heparin
 Keratan sulfate and
 Dermatan sulfate.
 Hyaluronic acid
■ (also called Hyaluronan or hyaluronate or HAA gel like
aminoglycan that is found in the tissue space, the synovial fluid of joints,
and the vitreous humor of the eyes and acts as a binding, lubricating, and
protective agent.

■ Hyaluronic acid is unique among the GAGs because it does not contain
any sulfate and is not found covalently attached to proteins.

■ It forms non-covalently linked complexes with proteoglycans in the ECM.

■ Hyaluronic acid polymers are very large (100-10,000 kD)and can displace a
large volume of water.
■ Found in :

Synovial fluid.
■ Vitreous humor of the eye.
■ Skin and loose connective tissue.
■ Cartilage
■ Epithelial
■ Neural tissues
 Structure of Hyaluronic acid

Repeated disaccharide units, composed of glucuronic acid and N-

acetylglucosamine .
 Functions of Hyaluronic acid

• Gel made of Hyaluronic acid hasgood resistance to compression, thus it acts

as lubricant and shock absorber in the synovial fluid.

• It makes extra cellular matrix loose, because of its ability to attract water.

• It forms an important part of cementing ground substance.

• Secreted byCercaria (infective stage of bilharziasis) to help penteration of skin.

• Hyaluronic acid is utilized extensively in various areas like
Cosmetic, Dietary supplement, Parenteral nutrition, and
Intraocular injection. HA is processed differently for the use
in these area of function based on specification and purity
of the product.

• Hyaluronic acid retains water like a sponge and has the ability
to absorb a thousand times more than its own weight and
play an important role in Tissue hydration,Lubication and
Cellular function. In short it is an excellent skin moisturizer.
 Chondroitin Sulphate
• Chondroitin sulfate is a sulfated glycosaminoglycan (GAG)
composed of a chain of alternating sugars (N-
acetylgalactosamine and glucuronic acid). It is usually
found attached to proteins as part of a proteoglycan.
• A chondroitin chain can have over 100 individual sugars, each
of which can be sulfated in variable positions and quantities.
• Chondroitin sulfate is a chemical that is normally found in
cartilage around joints in the body.
• Chondroitin sulfate is manufactured from animal sources such
as cow cartilage.
Structure of chondroitin sulphate:
• Found in :

 Cartilage
 Tendons
 Ligaments
 Bones
 Aorta
 Skin
 Cornea.
 Functions of chondroitin sulphates

• It has a role in binding collagen of cartilage and holding its fibers together.
Compressibility of cartilage in weight bearing is due to chondroitin sulfate.
• Chondroitin is in dietary supplements used as an alternative medicine to treat
osteoarthritis and also approved and regulated as a symptomatic slow-acting
drug for this disease (SYSADOA) in Europe and some other countries.
• It is commonly sold together with glucosamine. Chondroitin and
glucosamine are also used in veterinary medicine.
• It has a weak anticoagulant property.
 Heparin

• Heparin is Heterogeneous mixture of unbranched

polysaccharides chains.

• Alternating monosaccharides units of L-iduronic acid and D-

glucosamine.

• The molecular size in the natural extract is 2 to 40kDa.

• One third of the polysaccharide chains contains a specific

Anti-thrombin binding Pentasaccharide sequences.
• It isan anticoagulant present in liver
• It is produced mainly by mast cells of liver
Found in :
 Lungs

 Thymus

 Spleen

 Walls of large arteries skin and

 Small quantities in blood

 Structure of Heparin

• Disaccharide repeated units of

Iduronic acid with sulfate on C2
 Glucosamine with sulfate on C2 and C6.
 Heparin-Clinical Use
• Prophylactics of DVT and PE
• -Preventation of formation of thrombin
• -Low dose reginmens
• -High risk groups (acute myocardial infraction, Surgery)
• Treatment of DVT and PE
• -Preventation of further thrombin generation
• -High dose reginmens
• Coronary heart disease
• -Unstable angina
• -Acute myocardial infraction
 Functions of Heparin

• An anticoagulant present in liver and produced mainly by

mast cells of liver.

• Stimulates the release of lipoprotein lipase enzyme that hydrolyses the

absorbed fats.

• It is an extra cellular compounds, entering in the structure of receptors on the

cell surface.It participate in the cell adhesionandcell-cell interaction.
 Dermatan sulphate

• Structure: Disaccharide units composed of L-Iduronic acid

and N-acetyl galactosamine with sulfate on C4.

• It is widely distributed in animal tissue, resembling chondroitin sulfate and

Heparan sulfate.

• It has antithrombotic properties similar to heparin.

Structure of dermatan sulphate
 Functions of Dermatan Sulphate

• It is a predominant glycan present in skin.

• Dermatan sulfate may have roles

• Coagulation,
• Cardiovascular disease,
• Carcinogenesis,
• Infection,
• Wound repai and
• Fibrosis
 Keratan sulfate (KS)

• also called Keratosulfat

• Keratan Sulphateis either of two glycosaminoglycans (I and II),consisting
of repeating disaccharides units of N-acetylglucosamine and
galactose,but differing slightly in carbohydrate content and localization.

• It occurs in cartilage, the cornea, andin thnucleuss pulposusandisalso an

accumulation product in Morquio's syndrome.
• KS types are to be composed of three regions
• A linkage region, at one end of which the KS chain is
linked to the core protein
• A repeat region, composed of the -3Galβ1-4GlcNAcβ1-
repeating disaccharide unit and A chain capping region,
occurring at the opposite end of the KS chain to the protein linkage
region
• Thee designations KSI and KSII were originally assigned on the basis of
the tissue type from which the keratan sulfate was isolated
• KSII was isolated from corneal tissue and KSII from skeletal tissue
• Thee major differences occur in the way each KS type is joined to its
coreprotein.
• The designations KSI and KSII are now based upon these protein linkage
differences. KSI is N-linked to specific asparagine amino acids via
acetylglucosamine and KSII is O-linked to specific Serine or Threonine
amino acids vi a N-acetyll galactosamine

• The tissue based classification of KS no longer exists as KS types have

been shown to be non tissue specific

• A third type of KS (KSIII) has also been isolated from brain tissue that is O-
linked to specific serine or threonine amino acids via mannose.
Found in :

• Loose connective tissue KS (type-1)

• Cornea

• Cartilage and

• Bone.
 Structure of keratan sulphate
The disaccharide unit is composed of

( 1) Galactose and
(2 ) N-acetyl glucosamine with sulfate on C6. No
uronic acid
 Functions of Keratan Sulphate

• It occurs in cornea and skeletal tissues.

• It keeps cornea transparent.