Hepatic Xanthine Oxidase and Ferritin Iron in the Developing Rat

By A. MAzUR AND A. CARLETON T HE RESULTS of studies in our laboratory’ lend support to the hypothesis that the release of iron from ferritin stores in the liver is mediated by the enzyme xanthine oxidase acting as a dehydrogenase. In this reaction the reduced enzyme, formed as a result of oxidation of xanthine or hypoxanthine to uric acid, is reoxidized by some of the ferric iron of ferritin which is therefore reduced to the ferrous state. Reduced ferritin iron is less tightly bound to the protein than is the ferric form and dissociates easily in the presence of an avid iron acceptor such as the serum iron-binding protein transferrin. Since the newborn animal is dependent for its dietary iron on mother’s milk which is deficient in this element, it has been presumed that iron required by the preweanling animal for purposes of hemoglobin synthesis origmates from iron stored during fetal life.2 Westerfeld and Richert3 reported the virtual absence of liver xanthine oxidase in newborn rats, and early studies suggested the absence of this enzyme in liver of newborn human infants.4 If xanthine oxidase is responsible for the release of iron from hepatic ferritin at a rate greater than that which would normally occur as a result of protein turnover, xanthine oxidase must appear in the liver at a time coincident with the release of liver ferritin iron during the course of animal development. Results of the present study confirm an inverse relationship between ferritin iron content and xanthine oxidase activity in liver of the developing rat.