Identification of Iduronic Acid as the Major Sulfated Uronic Acid of Heparin

Oxidation of purified heparin with periodate destroyed about 30% of the total uronic acid and almost all of the glucuronic acid residues, suggesting that glucuronic acid was essentially nonsulfated. Heparin was degraded with nitrous acid at low temperature, and the resulting products were separated by gel chromatography followed by paper electrophoresis. Four fractions were isolated and identified as nonsulfated uronic acid monosaccharide (B), monosulfated uronosylanhydromannose disaccharide (C), disulfated uronosylanhydromannose disaccharide (D), and sulfated uronic acid monosaccharide (E), respectively. Fractions B and C contained both glucuronic acid and iduronic acid, whereas iduronic acid constituted almost all of the uronic acid present in Fractions D and E. The results obtained do not support a recent claim that treatment of heparin with nitrous acid causes a conversion of glucuronic acid residues to iduronic acid via epimerization at C-5. It is concluded that iduronic acid is the major sulfated uronic acid of heparin.