Effect of leucine and alpha-ketoisocaproic acid on NAD biosynthesis from tryptophan or nicotinic acid in the isolated rat liver cells.

The effects of leucine and alpha-ketoisocaproic acid on the NAD biosynthesis from (carboxyl-14C) nicotinic acid or (benzene ring-U-14C) tryptophan were investigated in the isolated rat liver cells. The quantities of NAD formed from tryptophan and nicotinic acid increased linearly during 60 min-incubation. Leucine, which was essentially not metabolized by the isolated liver cells, had no inhibitory effect on the NAD synthesis. On the other hand, alpha-ketoisocaproic acid, alpha-keto acid analogue of leucine, which was rapidly metabolized to ketone bodies, diminished a quantity and a specific radioactivity of NAD synthesized from both tryptophan and nicotinic acid to a similar extent. Palmitic acid, which was oxidized to ketone bodies by the isolated rat liver cells, also diminished an amount and a specific radioactivity of NAD synthesized from nicotinic acid. Ketone bodies exogenously added to the incubation medium exerted a similar inhibitory effect on NAD synthesis. Results demonstrate that substances which can be oxidized to ketone bodies are inhibitory to NAD biosynthesis from tryptophan and nicotinic acid in the isolated rat liver cells.