Transamination 3-hydroxykynurenine

Under normal conditions, the rate-limiting enzyme of the pathway is tryptophan dioxygenase (Section 8.3.2), and there is hide accumulation of intermediates. Kynurenine transaminase, the enzyme which catalyzes the transamination and ring closure of kynurenine to kynurenic acid, and of hydroxykynurenine to xanthurenic acid, has a high relative to the normal steady-state concentrations of its substrates in the liver. Kynureninase and kynurenine hydroxylase have lower values of K, so that there is normally litde accumuladon of kynurenine or hydroxykynurenine. 

Kynurenic acid and xanthurenic acid, side products of the reaction, are the products of the transamination of the a-amino group of kynurenine and 3-hydroxy-kynurenine to a-ketoglutaric acid in the presence of pyridoxal phosphate and an enzyme found in mammalian liver and kidney, kynurenine transaminase. The keto acid resulting from the transamination reaction condenses spontaneously. Liver homogenate also decarboxylates 3-hydroxykynurenine to yield 4,8-de-hydroxyquinoline. Kynurenase may catalyze the cleavage of the side chain of kynurenine or 8-hydroxy-kynurenine and lead to the formation of alanine and... 

The activities of both kynurenine hydroxylase and kynureninase are only slightly higher than that of tryptophan dioxygenase under basal conditions, and increased tryptophan dioxygenase activity in response to glucocorticoid action is accompanied by increased accumulation and excretion of kynurenine, hydroxykynurenine and their transamination products, kynurenic and xanthurenic acids. Impairment of the activity of either enzyme may impair the onward metabolism of kynurenine and so reduce the accumulation of aminocarboxymuconic semialdehyde, and hence the synthesis of NAD. 

This pathway occurs in a incomplete form in the vertebrate organism. In certain bacteria it is an important pathway for the total oxidation of tryptophan. The quinolinic pathway arises by transamination of kynurenine and hydroxykynurenine. The resulting products qiontaneously cyclize to form kynurenic and xanthurenic acids. 

Kynurenine is oxidized (again by atmospheric oxygen) to yield S-hydroxy-kynurenine and subsequently is cleaved to 3-hydroxyanthranilic acid and alanine. The fate of alanine has already been presented. Sidepaths from kynurenine and 3-hydroxykynurenine lead to kynurenic axid and xanthurenic acid] this reaction is explained as a transamination followed by spontaneous ring closure. 

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