Relation of uric acid metabolism to release of iron from hepatic ferritin.

In a previous study (1) we observed a marked increase in plasma iron of dogs subjected to drastic hypotension in the course of fatal experimental hemorrhagic shock. It was suggested that the origin of the increased plasma iron was storage ferritin of the liver and that the stimulus for its release was liver hypoxia. Anaerobic incubation of ferritin with liver slices resulted in an increase of its ferrous iron content which was now capable of dissociation for combination with iron-binding agents such as oc,ar’-dipyridyl or the plasma iron-binding protein. In the present study the mechanism of ferritin iron reduction and the nature of the compounds involved in this reaction have been investigated, It has been found that anaerobic rat liver slices produce large quantities of uric acid, hypoxanthine, and xanthine, which are freely diffusible into the medium. Of these compounds, only uric acid reduces ferritin iron directly. However, in the presence of ferritin, the oxidation of hypoxanthine or of xanthine by xanthine oxidase takes place anaerobically; in this reaction ferritin acts as an electron acceptor and its iron is reduced to the ferrous state. The reduction of ferritin iron is, therefore, brought about both by the dehydrogenase activity of xanthine oxidase and by the accumulated uric acid formed by this enzyme.