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Effects of a dietary excess of leucine and of the addition of leucine and 2-oxo-isocaproate on the metabolism of tryptophan and niacin in isolated rat liver cells

Published online by Cambridge University Press:  09 March 2007

David A. Bender
David A. Bender
Affiliation:
Department of Biochemistry, University College and Middlesex School of Medicine, University College London, Gower Street, London WC1E 6BT
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Abstract

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1. Feeding rats on a low-tryptophan, niacin-free, high-leucine diet resulted in impaired synthesis from tryptophan of the nicotinamide nucleotide coenzymes, NAD and NADP, and N1-methyl nicotinamide in isolated hepatocytes, compared with cells from animals fed on a low-tryptophan, niacin-free control diet providing an appropriate amount of leucine. This was accompanied by reduced accumulation of the tryptophan metabolites kynurenine, 3-hydroxykynurenine and xanthurenic acid.

2. With hepatocytes from animals fed on the low-tryptophan, niacin-free control diet, the addition of leucine to the incubation medium resulted in reduced synthesis of niacin from tryptophan, and a small increase in the accumulation of 3-hydroxykynurenine.

3. With hepatocytes from animals fed on the low-tryptophan, niacin-free control diet, the addition of 2-oxo-isocaproate to the incubation medium resulted in increased synthesis of NAD(P) and niacin, and increased accumulation of 3-hydroxykynurenine.

4. The results suggest that a dietary excess of leucine alters the activity of the enzymes of tryptophan→niacin metabolism, or the uptake of tryptophan into the liver, in a different manner from the simple inhibition and activation seen in experiments in vitro.

5. Differences between studies in isolated hepatocytes and intact animals suggest that extra-hepatic metabolism of tryptophan, catalysed by indoleamine dioxygenase, is more important than has been believed hitherto.

Type
Hormones, Metabolism
Information
British Journal of Nutrition , Volume 61 , Issue 3 , May 1989 , pp. 629 - 640
Copyright
Copyright © The Nutrition Society 1989

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