The preparation, properties, and inhibition of hypoxanthine dehydrogenase of avian kidney.

Renal enzymic mechanisms associated with the process of uric acid excretion in avain species have not been characterized. Early work on uric acid synthesis in pigeons established the kidney as the site of the terminal conversion of hypoxanthine to uric acid (1). A detailed study of this reaction in pigeon and chicken kidney here reported shows that uric acid synthesis in these tissues is catalyzed by a diphosphopyridine nucleotidedependent hypoxanthine dehydrogenase. Chicken liver contains a flavoprotein enzyme which was purified by Remy et al. (2) and characterized as a hypoxanthine dehydrogenase on the basis of its catalyzing uric acid synthesis from hypoxanthine in air at only 1% of the rate found in the presence of methylene blue. In a crude chicken liver system Morel1 (3) found uric acid synthesis associated with diphosphopyridine nucleotide reduction. A similar finding in a partially purified chicken liver preparation was reported by Felig and Wiley (4). Pigeon liver, however, does not synthesize uric acid (1). Avian species apparently utilize dehydrogenase mechanisms for uric acid production and in the case of kidney tissue where the reaction may have unique functional importance in terms of tubular secretory processes, the diphosphopyridine nucleotide dependence of the system is readily demonstrated. The purified chicken kidney hypoxanthine dehydrogenase reported herein differs in several respects from mammalian xanthine oxidase and from the chicken liver enzyme. Mahler (5) and De Renzo (6) have discussed the mechanism of action and chemical characterization of mammalian xanthine oxidase.