Tryptophan metabolism in vitamin B 6 -deficient mice

Abstract

Vitamin B 6 deficiency was induced in mice by maintenance for 4 weeks on a vitamin B 6 -free diet. Tryptophan metabolism was assessed by determining the urinary excretion of tryptophan metabolites, the metabolism of [ 14 C]tryptophan in vivo and the formation of tryptophan and niacin metabolites by isolated hepatocytes. The vitamin B 6 -deficient animals excreted more xanthurenic acid and 3-hydroxykynurenine, and less of the niacin metabolites N 1 -methyl nicotinamide and methyl-2-pyridone-4-carboxamide, than did control animals maintained on the same diet supplemented with 5 mg vitamin B 6 /kg. After intraperitoneal injection of [ 14 C]tryptophan, vitamin B 6 -deficient mice showed lower liberation of 14 CO 2 from [methylene- 14 C]tryptophan and [U- 14 C]tryptophan than did controls, indicating impairment of kynureninase ( EC 3.7.1.3) activity. There was no difference between the two groups of animals in the metabolism of [ring-2- 14 C]tryptophan. Hepatocytes isolated from the vitamin B 6 -deficient animals formed more 3-hydroxykynurenine and xanthurenic acid than did cells from control animals, but also formed more NADP and free niacin.