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.
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-oxoisocaproate 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.
Bender
D A
DA
Department of Biochemistry, University College and Middlesex School of Medicine, University College London.
D000818:Animals; D002208:Caproates / Q000494:pharmacology*; D066298:In Vitro Techniques; D007651:Keto Acids / Q000494:pharmacology*; D007737:Kynurenine / Q000031:analogs & derivatives / Q000378:metabolism; D007930:Leucine / Q000008:administration & dosage* / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D009243:NAD / Q000378:metabolism; D009525:Niacin / Q000378:metabolism*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014364:Tryptophan / Q000378:metabolism*; D014977:Xanthurenates / Q000378:metabolism
D002208:Caproates; D007651:Keto Acids; D014977:Xanthurenates; D009243:NAD; D009536:Niacinamide; D009525:Niacin; C005045:3-hydroxykynurenine; D007737:Kynurenine; C028330:xanthurenic acid; C013082:alpha-ketoisocaproic acid; D014364:Tryptophan; D007930:Leucine; C008472:N-methylnicotinamide