Sensitivity of rat liver xanthine oxidase to amino acid analogues.

There is ample evidence in the literature concerning the labile nature of rat liver xanthine oxidase and its dependence on dietary protein. McQuarrie and Venosa (1) observed a large drop in the enzyme activity when the protein content of the ration was reduced from 25 to 10 per cent. Miller (2) noticed that a 7 day inanition caused a loss of xanthine oxidase activity in rat liver which exceeded the loss of liver protein. Williams and Elvehjem (3) suggested that the activity of this enzyme could be used as a sensitive index of amino acid availability in dietary proteins. Westerfeld and Richert (4, 5) found that the xanthine oxidase of rat liver and intestine was influenced by the dietary intake of protein and by a factor in the water-insoluble fraction of liver. The latter was identified as molybdenum by De Renzo et al. (6). Litwack et al. (7) evaluated the quality of several proteins in terms of liver xanthine oxidase activity attained when these were fed to rats. A reduction in the activity of the enzyme due to deficiency of methionine (8), tryptophan (9), or vitamin Blz (10) was reported by Williams and coworkers. Litwack et al. (11) found that liver xanthine oxidase of rats fed a ration containing the essential amino acids for 28 days was twice as active as that of rats receiving the non-essential amino acids as the sole nitrogen source. The best results were obtained when the ration contained both essential and non-essential amino acids. Recently, Dietrich (12) reported an increase in mouse liver xanthine oxidase upon the administration of xanthine for 6 to 12 days. In this communication, the effect of three amino acid analogues on rat liver xanthine oxidase is reported. The administration of ,f3-3-thienyl-nnalanine or nn-propargylglycine was found to cause marked loss in the enzyme activity. nn-Ethionine and @-3-thienyl-nx,-alanine inhibited the repletion of xanthine oxidase in protein-depleted rats. The effect of p-3thienyl-nn-alanine was reversed by nn-phenylalanine.