Effect of L-leucine-supplemented diet on the nicotinamide adenine dinucleotide content of rat liver.

The hepatic nicotinamide adenine dinucleotide (NAD) content was significantly lower in rats fed a diet supplemented with 0.45-10% L-leucine for 1-3 weeks than in control rats fed laboratory chow (24.6% protein). High dietary levels of leucine did not affect the activity of hepatic tryptophan pyrrolase or quinolinate phosphoribosyltransferase, which are key enzymes in the tryptophan leads to NAD pathway. The increased hepatic NAD contents 4 hours after intraperitoneal injections of the NAD precursors L-tryptophan, niacin and nicotinamide were not influenced by excess dietary leucine. These observations suggest that decrease in the hepatic NAD content by excess dietary leucine is not due to alteration of NAD metabolism resulting from accumulation of leucine or its metabolite. The uptake of 1 mM L-[side chain-2,3-3H]tryptophan into isolated jejunal segments was inhibited markedly by 10 mM-leucine. Similar inhibitory effects were observed with 10 mM L-valine, L-isoleucine, L-phenylalanine and L-methionine, but not-L-lysine, L-aspartate, L-alanine or glycine. The radioactivity in portal blood after administration of a solution of 10 mumol of L-[side chain-3-14C]tryptophan in 1 ml of physiological saline by stomach tube was inhibited markedly by addition to the solution of 100 mumol of L-leucine or the other amino acids that inhibited L-tryptophan uptake by isolated jejunal segments. These findings strongly suggest that decrease in the liver NAD content by excess dietary leucine is mainly due to competitive inhibition by L-leucine of intestinal absorption of L-tryptophan.