Heparan Sulfate GlcA/GlcNAc Transferase
Heparan sulfates are sulfated glycosaminoglycans distributed on the cell surfaces and in the extracellular matrices of most tissues. The structurally related polysaccharide heparin is a highly sulfated variant of heparan sulfate that is exclusively produced by connective tissue mast cells. Heparan sulfate and heparin are synthesized as proteoglycans, and their biosynthesis is initiated by formation of a tetrasaccharide linkage region attached to a serine residue in the core protein (GlcAβ1-3Galβ1-3Galβ1- 4Xylβ1-O-Ser). After addition of a single α-GlcNAc residue, elongation proceeds by the action of glycosyltransferases, which add β1,4-GlcA and α1,4-GlcNAc units in alternating sequence to the nonreducing end of the growing polymer. Bifunctional glycosyltransferases, denoted EXT1 and EXT2, are believed to be involved in the sequential addition of GlcA and GlcNAc. Concomitant with chain elongation, further modifications occur through several enzymatic steps that generate a complex polysaccharide containing N-acetylated and N-sulfated GlcN residues, GlcA and IdoA acid units, and O-sulfate groups in various positions.
KeywordsHeparan Sulfate Chain Elongation Hereditary Multiple Exostosis Glycosyltransferase Activity Connective Tissue Mast Cell
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