Dr.

Astha Goyal
Dept. of Biochemistry
MGMC&H
 Introduction
Most mammalian cells are located in tissues where they
are surrounded by a complex extracellular matrix (ECM)
often referred to as “connective tissue.”

The extracellular space in animal tissues is filled

with a gel-like material, the extracellular matrix, also
called ground substance.
 Introduction
They holds the cells of a tissue together and provides a
porous pathway for the diffusion of nutrients and
oxygen to individual cells.
The extracellular matrix is composed of an interlocking
meshwork of heteropolysaccharides and fibrous
proteins.
Epithelial cells
extra-
cellular
matrix

Underlying cells cells

The ECM contains three major classes of
biomolecules:
(1) The structural proteins: collagen,
elastin, and fibrin;

(2) Specialized proteins such as fibrillin,

fibronectin and laminin;

(3) Proteoglycans
These molecules function in the extracellular matrix (ECM)
 GLYCOSAMINO
GLYCANS
Heteropolysaccharides in the body are the
glycosaminoglycans (GAGs).

These molecules are long unbranched polysaccharides

containing a repeating disaccharide unit.

Also known as mucopolysaccharides.

GAGs are highly negatively charged molecules (carboxy

& sulfate groups), with extended conformation that
imparts high viscosity to the solution.
GAGs are located primarily on the surface of
cells or in the extracellular matrix (ECM).

Special ability to bind large amount of water

producing gel like matrix, that forms the
bodies ground substance.
 GAGs
They differ form each other in a number of the following
properties:

1. Chain length.
2. Amino – sugar composition (Amino sugar – D-
Glucosamine or D-Galactosamine).
3. Uronic – Acid composition. (Uronic acid – D-Glucuronic
acid or L-Iduronic acid).
4. Linkages between these components.
5. Presence or absence of sulfate groups.
6. The attachment of sulfate to sugar molecule.
7. The nature of core protein linked to GAG.
8. The tissue and sub- cellular distribution of GAG.
 FUNCTIONS OF GAG
1. Structural component of extra cellular
matrix.
2. Contribute to the turgor of various tissues.
3. Acts as sieves in EC matrix.
4. Facilitate cell migration, acts as shock
absorber at joints.(Hyaluronic Acid)
5. Maintenance of compressibility of cartilage.
(Hyaluronic Acid & Chondroitin Sulphate)
 FUNCTIONS OF GAG
6. Have a structural role in sclera & in corneal
transparency. (Keratan Sulphate, Dermatan
Sulphate)
7. Acts as anticoagulant. (Heparin)
8. Determines the charge selectiveness of renal
glomerulus.(Heparan Sulphate)
9. Formation of cell membrane and synaptic
vesicles. (Heparan Sulphate)
The specific GAGs of physiological significance are:

Hyaluronic Acid
Dermatan Sulfate
Chondroitin Sulfate
Heparin
Heparan Sulfate
Keratan Sulfate
 Classification
GAGS

Sulphate free Sulphate containing

Hyaluronic acid Chondrotin Sulphate

Dermatan sulphate
keratan sulphate
Heparin
Heparan Sulphate

13
 1. Chondroitin sulfate
• Contains D-Glucoronic acid + Galactosamine.

• Most abundant GAG in body.

• Widely distributed in bone, cartilage & tendons.
• Function:
• In cartilage, it binds collagen & hold fibers in a tight
strong network.
• Role in Compressibility of cartilage in weight
bearing along with Hyaluronic acid.

• 2 types of chondroitin sulfate :

Sulphated at C4 or C6 group
2. Hyaluronic acid
Contains D-Glucoronic acid + Glucosamine.
It is sulphate free GAG.

It is sulphate free GAG.

Ground substance of synovial fluid of joints, vitreous
humor of eyes and connective tissues, tendon.

Hyaluronidase is an enzyme that breaks β-1 – 4 linkages.

Present in high concentration in testes, seminal fluid, & in

certain snake and insect venoms.
 Functions of Hyaluronic acid
Serves as a lubricant and shock absorbant in joints.

Acts as seives in extracelluar matrix.

Permits cell migration during embryogenesis, morpho-

genesis & wound repair.

Hyaluronidase enzyme of semen degrades the gel

around ovum & allows effective penetration of sperm
into ovum.
3. DERMATAN SULFATe

Contains L-iduronic acid + Galactosamine

Present in skin, cardiac valves & tendon.

Function :

Present in sclera of eye where it has important function

in maintaining overall shape of eye.
4. Heparin
• Contains D-Glucuronic acid + Glucosamine.
• It is the only intracellular GAG.
It is an anticoagulant (prevents blood clotting ).

Found in granules of mast cells that line the

arteries of lung, liver, kidney, spleen.

Strongly acidic due to presence of more

sulphate group.

Heparin helps in the release of the enzyme

lipoprotein lipase.

Helps to clear the lipidemia after fatty meal –

also called clearing factor.
5. Heparan sulfate
Same as heparin except some amino groups carry
acetyl group and % of sulphate groups are
smaller.

It is extracellular GAG .

Present in basement membrane & as a

ubiquitous component of cell surface.
6. KERATAN sulfate
• Contains D-Galactose + Glucosamine
•Only GAG with no uronic acid.
Found in cornea & tendon.

2 types :

Keratan sulfate І – cornea

Keratan sulfate ІІ – skeletal muscle

Function :
Maintains the corneal transparency.
 GAG Disaccharides units Functions
Amino sugar Uronic acid

1. Hyaluronic N-Acetyl Glucuronic acid Lubricant, shock absorber,

acid glucosamine facilitate cell migration

2. Condroitin N-Acetyl Glucuronic acid Provides endoskeletal structure

sulphate galactosamine

3. Keratan N-Acetyl Absent Transparency of cornea & overall

sulfate glucosamine- shape of the eye
galactose

4. Dermatan N-Acetyl Iduronic acid Maintains the shape of the tissues

sulfate galactosamine

5. Heparin Glucosamine Glucuronic acid Anticoagulant

6. Heparan ,, ,, Component of plasma membrane.

sulfate
Proteoglycan
Proteoglycan
mono-mers
typically are
bound non-
covalently to a
hyaluronic acid
molecule in
association with
linker protein in a
“bottle brush”
arrangement.
Thank you