Formation of the nicotinic acid analogue of diphosphopyridine nucleotide after nicotinamide administration.

The administration of nicotinamide to the mouse results in an Sto lo-fold increase in the diphosphopyridinc nucleotide content of the liver as previously reported by Kaplan et al. (l-3). Corresponding doses of nicotinic acid are far less effective than nicotinamide in eliciting a net synthesis of DPN (3). This is in contrast to the nicotinic acid specificity which has been observed for DPN synthesis in yeast autolysates (4) and human erythrocytes (5). The observation that nicotinamide is more effective than nicotinic acid as a precursor of DPN in the mouse liver suggested that nicotinamide conversion to the coenzyme form in liver might proceed through the widely accepted scheme involving nicotinamide mononucleotide as anintermediate (6, 7). In the meantime, Preiss and Handler (4, 8, 9) have shown that the synthesis of DPN from nicotinic acid in human erythrocytes and yeast autolysates proceeds through nicotinic acid nucleotides as intermediates. These authors also demonstrated by the use of Cr4nicotinic acid that the nicotinic acid analoguc of DPN was an intermediate in the synthesis in viva of DPN from nicotinic acid in rat liver (9). In our laboratory, the nicotinic acid analogue of DPN was isolated from the livers of mice given injections of nicotinamide (10). The present paper describes the study of the synthesis in vivo of DPN in mouse liver after injection of various precursors. Evidence is presented that the nicotinic acid analogue of DPN is a precursor of DPN even when the synthesis of DPN is elicited by the injection of nicotinamide. The fact that injected nicotinic acid does not cause as large a DPN increase as injected nicotinamide may possibly be explained in terms of substrate inhibition.