Studies on the Biosynthesis of Nicotinamide Adenine Dinucleotide: III. COMPARATIVE IN VIVO STUDIES ON NICOTINIC ACID, NICOTINAMIDE, AND QUINOLINIC ACID AS PRECURSORS OF NICOTINAMIDE ADENINE DINUCLEOTIDE

Abstract

In order to investigate the biosynthesis of nicotinamide adenine dinucleotide in vivo and to evaluate comparatively the quantitative significance of three precursors, nicotinic acid, nicotinamide, and quinolinic acid, the radioactive substrates were injected directly into the portal vein of mice, and the radioactive compounds in the liver were analyzed. When administered in small doses, nicotinic acid was a much better precursor of NAD than nicotinamide. The incorporation of nicotinic acid-14C into NAD proceeded almost linearly up to 10 min, thereafter NAD-14C gradually decreased to about one-half by 10 hours. In contrast, nicotinamide-14C injected in this way was not utilized significantly for the synthesis de novo of NAD during the 1st hour after the injection. Quinolinic acid-14C hardly penetrated into the liver cells. On the contrary, when administered in large quantities, nicotinamide was a much better precursor of NAD in the liver than nicotinic acid. With a large dose of nicotinamide-14C as substrate, the total radioactivity in the liver decreased rapidly during the 1st hour and then increased up to almost 8 hours after the injection. During the initial phase, the incorporation of 14C into NAD was almost insignificant, but NAD-14C in the liver started to increase about 1 hour after the injection with the concomitant increase of the total radioactivity in the liver. Analyses of the distribution of 14C in various organs and tissues indicated that a large portion of nicotinamide-14C was first excreted from liver, accumulated in the gastrointestinal tract, deamidated to nicotinic acid, reabsorbed into the liver, and served as precursor to NAD over a prolonged period of time.