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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

From the ¹ From the Department of Medical Chemistry, Kyoto University Faculty of Medicine, Kyoto, Japan

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.

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