Biosynthesis of D-glucaric acid in mammals: a free-radical mechanism?

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.