Heparan sulfate C5-epimerase is essential for heparin biosynthesis in mast cells.
Biosynthesis of heparin, a mast cell-derived glycosaminoglycan with widespread importance in medicine, has not been fully elucidated. In biosynthesis of heparan sulfate (HS), a structurally related polysaccharide, HS glucuronyl C5-epimerase (Hsepi) converts D-glucuronic acid (GlcA) to L-iduronic acid (IdoA) residues. We have generated Hsepi-null mouse mutant mast cells, and we show that the same enzyme catalyzes the generation of IdoA in heparin and that 'heparin' lacking IdoA shows a distorted O-sulfation pattern.
Feyerabend
Thorsten B
TB
Department of Immunology, University of Ulm, D-89070 Ulm, Germany.
Li
Jin-Ping
JP
Lindahl
Ulf
U
Rodewald
Hans-Reimer
HR
D000818:Animals; D002238:Carbohydrate Epimerases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002240:Carbohydrate Sequence; D020723:Glucuronic Acid / Q000737:chemistry; D019812:Heparan Sulfate Proteoglycans / Q000737:chemistry; D006493:Heparin / Q000096:biosynthesis* / Q000737:chemistry; D006497:Heparan Sulfate / Q000737:chemistry; D006801:Humans; D007067:Iduronic Acid / Q000737:chemistry; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000737:chemistry; D013997:Time Factors
D002238:Carbohydrate Epimerases; D020723:Glucuronic Acid; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin; D006497:Heparan Sulfate; D007067:Iduronic Acid; D011134:Polysaccharides; C430881:heparin-heparan sulfate-glucuronic acid C5-epimerase