title: Biosynthesis of D-glucaric acid in mammals: a free-radical mechanism?
abstract: In the presence of iron salts and hydrogen peroxide, D-glucuronic acid was converted into D-glucaric acid. The reaction was strongly inhibited by free-radical scavengers and is ascribed to the action of the hydroxyl radical. The formation of D-glucarate was dependent upon pH and occurred in the presence of some iron-complexing agents. The first product of oxidation was a lactone that was a strong inhibitor of beta-D-glucuronidase and assumed to be D-glucaro-1,5-lactone. Microsomal preparations in the presence of NADPH also produced D-glucarate from D-glucuronic acid, presumably due to formation of hydrogen peroxide, and the product was an inhibitor of beta-D-glucuronidase. Superoxide did not produce D-glucarate from D-glucuronate. The cytochrome P450 system is more likely than "glucuronolactone dehydrogenase" to be responsible for the production of D-glucaric acid in vivo.
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D002237:Carbohydrate Dehydrogenases / Q000378:metabolism*; D005937:Glucaric Acid / Q000096:biosynthesis*; D005965:Glucuronates; D020723:Glucuronic Acid; D005966:Glucuronidase / Q000378:metabolism*; D006861:Hydrogen Peroxide; D007501:Iron; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012627:Sebaceous Glands / Q000201:enzymology*; D013400:Sugar Acids / Q000096:biosynthesis*; D013737:Testis / Q000201:enzymology*
chemical_list: C045076:Fenton's reagent; D005965:Glucuronates; D013400:Sugar Acids; D020723:Glucuronic Acid; D006861:Hydrogen Peroxide; D007501:Iron; D002237:Carbohydrate Dehydrogenases; C020645:glucuronolactone reductase; D000444:Aldehyde Dehydrogenase; D005966:Glucuronidase; D005937:Glucaric Acid