Effect of branched chain .ALPHA.-keto acids on kynurenine 3-hydroxylase from rat liver.

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In the preceding paper, we found that branched chain α-keto acids, α-ketoglutarate and pyruvate were inhibitory to kynurenine 3-hydroxylase [EC 1.14.1.2] from Saccharomyces (Shin, M, et al. (1982): J. Nutr. Sci. Vitaminol., 28, 191-201). As kynurenine 3-hydroxylase is reported to be a rate-limiting enzyme in the tryptophan-NAD pathway in rats, branched chain amino acids, branched chain a-keto acids and several other keto acids were tested for their effects on kynurenine 3-hydroxylase activity in the mitochondrial outer membrane fraction prepared from rat liver. In contrast with the yeast enzyme, the rat liver enzyme was resistant to α-keto acid-inhibition and more than 70% of the enzyme activity was maintained even in the presence of 20mM of each α-keto acid. The present result implies that the mechanism of the hepatic NAD-lowering effect of leucine in rats might be completely different from that operative in Saccharomyces.
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