Allopurinol and iron metabolism in man.

T HE ENZYME, XANTHINE OXIDASE, is thought to play a central role in the mobilization of storage iron from the liver.1 In the presence of xanthine oxidase, xanthine is oxidized to uric acid, the enzyme acting as electron acceptor in the oxidation reaction . ‘ Coupled to the oxidation of uric acid is the reduction of ferric ferritin to the ferrous state. The livers of immature rats contain very little xanthine-oxidase activity, and the hepatic ferritin content is greater than that found in normal adult rats.4 As these animals approach maturity, xanthine-oxidase activity rapidly rises to the adult level, and there is a parallel fall in ferritin to normal adult levels.4 In the adult rat, xanthine oxidase is present is excess, such that the factor limiting the rate of release of ferritin iron is the cellular concentration of xanthine and hypoxanthine.5 In the rare disorder, xanthinuria, there is a gross deficiency of xanthine oxidase. One such patient, a 47 year old male, also has hemochromatosis.6 Mazur and Sackler5 have presented evidence that xanthine-oxidase activity is low in hepatic tissues in hemochromatosis and cirrhosis. Excessive hepatic iron deposits in cirrhosis may be the result of acute and chronic deficiencies of protein.7’8 The same is true in patients with kwashiorkor, and, in addition, hepatic xanthine-oxidase activity is low and returns to normal levels following administration of diet containing adequate amounts of protein.9 Xanthine-oxidase activity is low in cirrhotic livers and is associated with extensive hepatic iron deposits.10’