Quantitative Studies on Tryptophan Metabolism in the Pyridoxine-deficient Rat

Abstract

Female rats weighing about 40 g were fed a pyridoxine-deficient diet. Control animals received the same diet supplemented with 2.5 mg of pyridoxine hydrochloride/kg of diet. After 2 or 3 weeks the animals were given 40 mg of l-tryptophan by the intraperitoneal route. Urine collected for 24 hours before and after the supplementation with tryptophan was analyzed for several tryptophan metabolites. The pryidoxine-deficient rats excreted abnormally large quantities of kynurenine, 3-hydroxykynurenine, acetylkynurenine and xanthurenic acid as compared with the control rats. The deficient animals and the controls excreted similar quantities of indoxyl sulfate, anthranilic acid glucuronide, o-aminohippuric acid and kynurenic acid. Although precursors of both xanthurenic and kynurenic acids were increased in the urine of the pyridoxine-deficient animals after a loading dose of tryptophan, kynurenic acid excretion was no greater than that of the control animals. These results are consistent with the view that the enzyme system concerned with the transamination of kynurenine to form kynurenic acid is distinct from the enzyme system which transaminates hydroxykynurenine to form xanthurenic acid. It is also possible that there is an alternate pathway for xanthurenic acid synthesis which remains active in pyridoxine deficiency.