Hetero poly saccharides mainly glycosaminoglycans

GLUCOSAMINO GLYCANS(GAGS)

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HETERO POLY SACCHARIDES• GLYCOSAMINOGLYCANS

• GLYCO CONGUGATESI. PROTEOGLYCANSII. GLYCOPROTEINSIII. GLYCOLIPIDS

GLYCOSAMINO GLYCANS Hetero glycans ;long chain negatively charged

unbranched poly saccharide units .

COMPOSITIONI. Repeating Disaccharide unitsII. Esterified sulfated groups

Disaccharide units may be ACIDIC SUGAR Oxidation at C-6 of Glucose producing ,I. D- Glucoronic AcidII. L- Iduronic Acid AMINO SUGAR Substitution of OH group at C-2 by NH2

I. Glucosamine II. Galactosamine

ESTERIFIED SULFATE GROUP

Present on C-4 /C-5 or non Acetylated N

MAJOR CLASSES OF GAGSI. CHONDROITIN (4 & 6 ) SULFATESII. KERATIN SULFATES 1 & 2III. DERMATIN SULFATE IV. HEPARIN V. HEPARIN SULFATE VI. HYALURONIC ACID

GAGS differ from each other in ,i. Amino sugar componentii. Uronic acid compositioniii. Linkages between the componentsiv. Chain length of the Disaccharidesv. Sulfate groupsvi. Position of SO4 groups.

PHYSICAL PROERTIES Long chain unbranched molecules. Polyanions , Highly negatively charged (SO4,COOH,CO-CH3).

Appear in extended form in solution.

Show strong repulsive forces among each others.

Contain large number of OH groups surrounded by shell of water molecules. repel each other

Occupy space (strong hydration) Slip past each others, and have lubricating &

cushioning effects.

When brought together ,GAGS slip past each other .

When compressed ,water is squeezed out & GAGS are forced to occupy smaller volume .

When compression is released ,they spring back to their original volume ,this gives them resilience & shock absorptive properties i.e. of synovial fluid & vitreous humor of the eye .

CHONDROITIN SULFATE

Most abundant GAG in the body . Provides an endoskeleton structure . Present in Cartilages , Tendons ,Ligaments &

Aorta .Helps to maintain their shapes . In the cartilage , it binds to the Collagen to hold its’

fibers in a tough ,strong net work . OSTEO ARTHRITIS the amount of Chondroitin so4 ↓ while that of

Hyaluronic acid ↑with age .

DERMATIN SULFATE

Found in Skin , Blood vessels ,Heart valves & Cornea .in the Cornea it along with Keratin SO4 lies between collagen fibers leading to CORNEAL TRANSPARENCY .

Its’ presence in the Sclera maintains overall shape of the eye .

Major GAG synthesized by arterial smooth muscle cells ,

It binds with plasma low density Lipoproteins

ATHEROSCLEROSISPlaque formation ( VLDL + Smooth

muscle proliferation )

KERATIN SULFATE

TYPE 1 ( cornea ,cartilage ) Type 2 ( loose connective tissue along

with Chondroitin so4 & Hyaluronic acid). Maintains corneal transparency.

HEPARIN

Intra cellular GAG Found in the granules of mast cells

lining of arterial cells in liver ,lungs & skin .

Anticoagulant Binds with Factors 9 & 11 Interacts with plasma Antithrombin to bind with

Thrombin ,preventing clot formation . Specifically binds to Lipoprotein Lipase enzyme

present in capillary walls & releases it in the circulation.

HEPAERIN SULFATE Same as Heparin except , i. Glucosamine at some places are

Acetylated .ii. Has fewer SO4 groups .iii. Extra cellular GAG . Acts as receptor, attached to integral

proteins of plasma membrane. Present in the basement membrane of renal

tubules . Participate in cell-cell communication ,& cell

growth . METASTASIS OF TUMOUR CELLS

HYALURONIC ACID

Unsulfated ,non covalently attached to proteins . Widely distributed among animals & bacteria. Present in Synovial fluid ,vitreous humor ,umblical cord, loose

connective tissue & cartilage. High concentration in embryonic tissue permits cell

migration during morphogenesis. Helps in wound repair . Gives compressibility to cartilage . Attracts water & acts as lubricant ,shock absorbent. Tumor cell migration through extra cellular matrix .

DEGRADATION OF GAGS Slow turn over, Half life being Days to

weeks .i. Phagocytosisii. Lysosomal degradation by acid

hydrolases at pH 5. Endoglycosidases cleave the poly

saccharides chains into oligosaccharides .

Further degradation through exoglycosidases & Sulfatases .

MUCOPOLYSACCHARIDOSES Hereditary ,(1:25000) Progressive disorder . CAUSATIVE MECHANISM mutation in gene encoding Lysosomal Hydrolases for GAGS degradation

Defective Lysosomal Hydrolases

Accumulation of substrates in liver ,spleen bones, skin, cornea & central nervous system

CLINICAL FEATURES i. Hepato splenomegalyii. Skeletal deformitiesiii. Coarse facial featuresiv. mental retardation v. Corneal cloudingvi. Presence of oligosaccharide units in

urine

DIAGNOSIS & TREATMENT Presence of oligosaccharides in urine Cellular assays of Acid Hydrolases

TREATMENT i. Cord blood transplantii. Bone marrow transplantiii. Enzyme replacement therapy