Factors affecting the induction of xanthine oxidase of mouse liver.

In 1948 Keith et al. (1) demonstrated that in chicks fed a folic aciddeficient diet liver xanthine oxidase activity was far higher than that observed in birds receiving adequate levels of folic acid. It was postulated (2, 3) that 6-formylpteridine, a potent inhibitor of xanthine oxidase in vitro, was biologically active in controlling the oxidation of xanthine and hypoxanthine in vivo, since 6-formylpteridine is generally a contaminant of folic acid preparations. It was subsequently shown that this could not be the case (4), and it has been inferred that a folic acid deficiency gives rise to abnormally high xanthine oxidase activity rather than that dietary folic acid depresses normal enzymatic activity (4, 5). Recently, it has been demonstrated that a vitamin E deficiency increases xanthine oxidase activity of rabbit liver (6). This increase in enzymatic activity was observed to occur only in the liver, the low xanthine oxidase activities of other rabbit tissues being unaltered by a vitamin E deficiency (7). A similar phenomenon was observed in the case of the folic acid-deficient chick (5). These observations, the importance of xanthine and hypoxanthine oxidation in purine catabolism, and the fact that both of the above deficiencies are accompanied by a derangement of purine metabolism lead one to speculate regarding the possible adaptation of this enzyme in the presence of elevated concentrations of purines. The data presented in this paper suggest that xanthine oxidase of mouse liver may be an adaptable or inducible enzyme.