Glycosaminoglycans

GAS's also known as Mucopolysaccharides are heteropolysaccharides and plays a variety of role in human body specially in connective tissue.

1. Dr. Astha Goyal Dept. of Biochemistry MGMC&H

2. 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 .

3. 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 .

4. Epithelial cells extra- cellular matrix Underlying cells cells

5. The ECM contains three major classes of biomolecules : (1) The structural proteins: collagen, elastin , and fibrin; (2) S pecialized proteins such as fibrillin , fibronectin and laminin ; ( 3) Proteoglycans

6. These molecules function in the extracellular matrix (ECM)

7. GLYCOSAMINO GLYCANS Heteropolysaccharides in the body are the glycosaminoglycans (GAGs). These molecules are long unbranched polysaccharides containing a repeating disaccharide unit . A lso known as mucopolysaccharides . GAGs are highly negatively charged molecules ( carboxy & sulfate groups ) , with extended conformation that imparts high viscosity to the solution.

8. 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 .

9. GAGs They differ form each other in a number of the following properties: Chain length. Amino – sugar composition ( Amino sugar – D-Glucosamine or D- Galactosamine ). Uronic – Acid composition . ( Uronic acid – D- Glucuronic acid or L- Iduronic acid ). Linkages between these components. Presence or absence of sulfate groups. The attachment of sulfate to sugar molecule. The nature of core protein linked to GAG. The tissue and sub- c ellular distribution of GAG.

10. FUNCTIONS OF GAG Structural component of extra cellular matrix . Contribute to the turgor of various tissues. Acts as sieves in EC matrix. Facilitate cell migration, acts as shock absorber at joints. ( Hyaluronic Acid) Maintenance of compressibility of cartilage . ( Hyaluronic Acid & Chondroitin Sulphate )

11. FUNCTIONS OF GAG Have a structural role in sclera & in corneal transparency. ( Keratan Sulphate , Dermatan Sulphate ) Acts as anticoagulant. (Heparin) Determines the charge selectiveness of renal glomerulus .( Heparan Sulphate ) Formation of cell membrane and synaptic vesicles. ( Heparan Sulphate )

12. The specific GAGs of physiological significance are: Hyaluronic Acid Dermatan Sulfate Chondroitin Sulfate Heparin Heparan Sulfate Keratan Sulfate

13. Classification 13 GAGS Sulphate free Sulphate containing Hyaluronic acid Chondrotin Sulphate Dermatan sulphate keratan sulphate Heparin Heparan Sulphate

14. Contains D- Glucoronic acid + Galactosamine . Most abundant GAG in body. 1. Chondroitin sulfate

15. 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 C 4 or C 6 group

16. 2. Hyaluronic acid Contains D- Glucoronic acid + Glucosamine. It is sulphate free GAG . It is sulphate free GAG.

17. 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.

18. 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.

19. 3. DERMATAN SULFAT e Contains L- iduronic acid + Galactosamine

20. Present in skin, cardiac valves & tendon. Function : Present in sclera of eye where it has important function in maintaining overall shape of eye.

21. 4. Heparin Contains D- Glucuronic acid + Glucosamine. I t is the only intracellular GAG.

22. 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 .

23. 5 . Heparan sulfate Same as heparin except some amino groups carry acetyl group and % of s ulphate groups are smaller . It is extracellular GAG . Present in basement membrane & as a ubiquitous component of cell surface.

24. 6. KERATAN sulfate Contains D- Galactose + Glucosamine Only GAG with no uronic acid.

25. Found in cornea & tendon. 2 types : Keratan sulfate І – cornea Keratan sulfate ІІ – skeletal muscle Function : Maintains the corneal transparency.

26. GAG Disaccharides units Functions Amino sugar Uronic acid 1. Hyaluronic acid N-Acetyl glucosamine Glucuronic acid Lubricant, shock absorber, facilitate cell migration 2. Condroitin sulphate N-Acetyl galactosamine Glucuronic acid Provides endoskeletal structure 3. Keratan sulfate N-Acetyl glucosamine- galactose Absent Transparency of cornea & overall shape of the eye 4. Dermatan sulfate N-Acetyl galactosamine Iduronic acid Maintains the shape of the tissues 5. Heparin Glucosamine Glucuronic acid Anticoagulant 6. Heparan sulfate ,, ,, Component of plasma membrane.

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

28. Thank you