Purine catabolism in molybdenum deficiency.

A low protein diet (1, 2) removed about three-fourths of the xanthine oxidase from the entire rat (3), while a purified diet containing tungstate reduced the tissue xanthine oxidase to a level at which it could not, be detected manometrically (4) ; neither of these dietary procedures had any effect on the uric acid or allantoin excretion by this species. Chicks fed a tungstate-containing diet excreted a mixture of xanthine, hypoxanthine, and uric acid in response to the marked depletion of tissue xanthine dehydrogenase and molybdenum (4). Either (a) small amounts of xanthine oxidase persisted in the tissues of tungstate-fed rats but escaped detection by the manometric procedure, or (b) uric acid was formed in rats by a pathway which was not molybdenum-dependent, e.g. by the oxidation of inosinic acid to xanthylic acid (5) and further oxidation to uric acid ribotide. Such a possibility was explored previously with rat livers in which the xanthine oxidase had been removed by feeding a low protein diet, but no alternative pathway which bypassed the Mo-containing xanthine oxidase could be found (6). In the previous study (6) an alternative system might, have escaped detection if it were also removed from the liver by a protein deficiency. This problem has therefore been reinvestigated with livers from which the xanthine oxidase was removed by tungstate feeding. Although no xanthine oxidase activity could be detected manometrically in the deficient livers, enough of the enzyme was retained to account for the formation of the normal daily output of uric acid and allantoin by the deficient rats. From a study of net oxygen consumption as well as uric acid and allantoin production from various nucleoside and nucleotide substrates, there were no indications that xanthine oxidase was bypassed in the formation of uric acid by the rat.