Heparin-Heparansulfate Related GlcA C5-Epimerase
The glucuronyl C5-epimerase is a key enzyme in the biosynthesis of heparan sulfate (HS) and heparin, a group of polysaccharide composed of alternating hexuronic acid and glucosamine residues. Both species are synthesized as proteoglycans, but on different core proteins (Esko 1991). Heparin is essentially only expressed by connective-tissue-type mast cells, whereas HS is produced by all other mammalian (and many nonmammalian) cells. The process of HS and heparin biosynthesis is initiated by glycosylation of the core proteins through covalently binding to the serine residues in respective core proteins. The process generates polysaccharide sequences that are composed of alternating d-glucuronic acid (GlcA) and N-acetyl-d-glucosamine (GlcNAc) units with varied chain length. The resulting polymer of (GlcAß1,4-GlcNAca1,4)n disaccharide repeats is modified through a series of reactions, including N-deacetylation/N-sulfation of GlcNAc residues, C5-epimerization of the GlcA units to yield l-iduronic acid (IdoA) residues, and finally O-sulfation at various positions of the sugar residues (Lindahl and Li 2009). The modification reactions occur in a stepwise manner, such that early steps provide the substrates for subsequent reactions. Heparin is extensively sulfated and has a high content of IdoA (typically 50–90 % of the total hexuronic acid), whereas HS has a more varied structure, generally less sulfated and with lower IdoA content than heparin (typically 30–55 % of the total hexuronic acid) (Taylor et al. 1973).
KeywordsHeparan Sulfate Hexuronic Acid GlcA Residue Mouse Embryo Fibroblast Cell Crude Heparin
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