Effect of branched chain alpha-keto acids on kynurenine 3-hydroxylase from rat liver.
In the preceding paper, we found that branched chain alpha-keto acids, alpha-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 alpha-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 alpha-keto acid-inhibition and more than 70% of the enzyme activity was maintained even in the presence of 20 mM of each alpha-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.
D000597:Amino Acids, Branched-Chain / Q000494:pharmacology*; D000818:Animals; D007425:Intracellular Membranes / Q000201:enzymology; D007651:Keto Acids / Q000494:pharmacology*; D050601:Kynurenine 3-Monooxygenase; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013347:Subcellular Fractions / Q000201:enzymology
D000597:Amino Acids, Branched-Chain; D007651:Keto Acids; D006899:Mixed Function Oxygenases; D050601:Kynurenine 3-Monooxygenase