Kynurenine hydroxylase and

Studies with [ C] tryptophan in animals and isolated hepatocytes show that leucine does inhibit the synthesis of NAD from tryptophan, inhibiting metabolism at the level of kynurenine hydroxylase and kynureninase, causing the accumulation of intermediates. In isolated hepatocytes, the more... 

Chiarugi A, Carpenedo R, Moroni F (1996) Kynurenine disposition in blood and brain of mice Effects of selective inhibitors of kynurenine hydroxylase and of kynureninase. J Neurochem 67 692-698. 

Chiarugi A, Carpenedo R, Molina MT, Mattoli L, Pellicciari R, Moroni F (1995) Comparison of the neurochemical and behavioural effects resulting from the inhibition of kynurenine hydroxylase and/or kyureninase. J Neurochem 65 1176-1183... 

Moroni F, Carpenedo R, Chiarugi A (1996) Kynurenine hydroxylase and kynureninase inhibitors as tools to study the role of kynurenine metabolites in the central nervous system. Adv Exp Med Biol 398 203-210... 

The activities of three enzymes, tryptophan dioxygenase, kynurenine hydroxylase and kynureninase, affect the rate of formation of aminocarboxymuconic semialdehyde, as may the rate of uptake of tryptophan into the liver. 

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. 

The conversion of tryptophan to nicotinic acid in vivo is depicted in Figure 1. The rate of conversion of tryptophan to niacin and the pyridine nucleotides is controlled by the activities of tryptophan dioxygenase (known alternatively as tryptophan pyrrolase), kynurenine hydroxylase, and kynureninase. These enzymes are, in turn, dependent on factors such as other B vitamins, glucagon, glucocorticoid hormones, and estrogen metabolites, and there are various competing pathways which also affect the rate of conversion. For these reasons, a variety of nutrient deficiencies, toxins, genetic and metabolic abnormalities, etc. can influence niacin status and requirements. 

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