Download LEARNING OBJECTIVES

LEARNING OBJECTIVES
Biochemistry of Connective Tissue
At the end of the lecture students should be able to:
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Define extracellular matrix or Connective tissue
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Enlist different components of Connective tissue
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Describe proteoglycans
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List different types of Glycosaminoglycans (GAG)
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Discuss the biosynthesis of GAG
LECTURE OUTLINE
Biochemistry of Connective Tissue
Definition

Most mammalian cells are located in tissues where they are surrounded by a
complex extracellular matrix (ECM) referred to as “connective tissue”
Components
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3 major classes of biomolecules
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The structural proteins  includes  collagen, elastin & fibrillin
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Specialized proteins  fibronectin & laminin
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Proteoglycanes
Proteoglycans
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Giant molecule CHO 95%, Protein 5%
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CHO  glycosaminoglycans
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Core protein, tissue distribution and function.
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30 types  syndecan, aggrecan, perlecan, decorin, biglycan and fibromodulin
Glycosaminoglycans
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Unbranched polysaccharides  repeating disaccharides units with one
component of amino sugar (D-glucosamine, D-galactosamine), Uronic acid.
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7 types are present
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Hyaluronic acid, chondroitin sulphate, Keratan sulphate I and II, heparin,
heparan sulphate dermaten sulphate.
Hyaluronic Acid
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Unbranched chain of repeating diasaccharides.  GlcUA and GlcNAc
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Widely distributed.  Bacteria, animal tissues, Synovial fluid, cartilage.
Chondroitin Sulphate
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Present in Cartilage
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Proteoglycans linked to chondroitin sulphate  Xyl-Ser-O-glycosidic bond
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Repeating disaccharides  GlcUA and GalNAc
Keratan Sulphate I & II
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Consists of repeating  Gal-GlcNAc diasaccharides unit  sulphate unit
attached 6’ position GlcNAc
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Type I is abundant in cornea
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Type II is found in loose connective tissue
Heparin
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Granules of mast cells, liver, lung and skin.
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Disaccharides glucosamine (GlcN) and uronic acids
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Amino groups of the GlcN residues are N- sulfated
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The protein molecule is unique  serine and glycine residues
Heparan Sulphate
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Cell surface
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Cantains GlcN with fewer N – sulfate
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Its predominant uronic acid is GlcUA
Dermatan Sulphate
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Animal tissues.
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Cantains both IdUA-GalNAc and GlcUA-GalNAc disaccharides.
Biosynthesis of Glycosaminoglycans
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A. Attachment to core proteins
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B. Chain Elongation
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C. Chain Termination
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D. Modification
Attachment to core proteins
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Starts in ER and completed in Golgi app.
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The linkage between GAGs and core protein  One of three types
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O-glycosidic between xylose and serine  proteoglycans  Gal-Gal-xyl-ser---
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O-glycosidic between GalNAc & ser  Keratan sulfate II
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O-glycosidic between GlcNAc amide N of Asn
Chain Elongation
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By addition of oligosaccharides 

Glycosyltransferase.
Chain Termination
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Sulfation  sugar
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The progression of the growing GAG chain away from the membrane site
where catalysis occurs
Modification
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Numerous chemical modification occur
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Introduction of sulfate group on to GalNAc  Sulfotransferases
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Epimerase  Catalyses conversion of glucuronyl to iduronyl residues.