Effect of fatty acids on xanthine dehydrogenase synthesis in the chick

Abstract

Previously it has been shown that feeding allopurinol to chicks causes a 2- to 3-fold increase in liver xanthine dehydrogenase (XDH) and, furthermore, that this increase is due to an increase in the rate of enzyme synthesis. In such chicks it was found that the concentration of hypoxanthine plus xanthine was elevated several fold, and on this basis it was suggested that allopurinol acts by means of substrate-induced synthesis of XDH. Results in the present paper show that feeding adenine induces a doubling in the level of chick liver XDH, an increase in the rate of enzyme synthesis and that, when adenine and allopurinol are fed at the same time, the level of this enzyme can be increased approximately 6-fold. In addition it was found that adenine causes an increase in hypoxanthine plus xanthine concentration in chick liver and that the combination causes an even higher concentration of these substances. Careful examination of the time response of hypoxanthine plus xanthine concentration changes and enzyme activity changes shows that the substrates increase in concentration prior to the increase in enzyme activity. These results suggest that regulation of chick XDH activity involves substrate induction of enzyme synthesis.