Utilization of tryptophan, nicotinamide and nicotinic acid as precursors for nicotinamide nucleotide synthesis in isolated rat liver cells

1. Incubation of isolated rat hepatocytes with nicotinamide or nicotinic acid showed that while both vitamers were taken up from the incubation medium, neither was utilized to any significant extent as a precursor of the nicotinamide nucleotide coenzymes, NAD and NADP, and neither was capable of preventing the loss of nucleotides that occurs on incubating the cells. 2. Incubation of hepatocytes with tryptophan showed that de novo synthesis from tryptophan permitted replacement of the nucleotides lost during incubation; at high concentrations of tryptophan there was an increase above the initial intracellular concentration of NAD(P). Incubation of hepatocytes with tryptophan also resulted in the formation and release from the cells of a considerable amount of niacin, as well as the two principal metabolities of NAD(P), N1-methyl nicotinamide and methyl pyridone carboxamide. 3. It is suggested that, in the liver, performed niacin is not utilized for nucleotide synthesis, and indeed the function of the liver appears to be synthesis of niacin from tryptophan, and its release for use by extrahepatic tissues that lack the pathway for de novo synthesis of nicotinamide nucleotides from tryptophan.