Niacin biosynthesis in the developing chick embryo.

In 1945, Krehl et al. (1) observed that tryptophan and nicotinic acid were mutually interchangeable, within limits, in supporting the growth of rats. Since that time considerable evidence has accumulated which demonstrates the biosynthesis of niacin from tryptophan in the rat and other animals. Studies with Neurospora and mammals have demonstrated that the pathway from tryptophan goes through kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, an unstable intermediate, quinolinic acid, and hence to nicotinic acid (2). The role of quinolinic acid as an obligatory intermediate in the conversion of tryptophan to niacin in animals and Neurospora has been questioned by some workers (3, 4). Henderson and Hirsch (5) first identified quinolinic acid as a metabolite of tryptophan in the rat. Quinolinic acid injections caused a 3-fold increase in the excretion of N-methylnicotinamide (6), and quinolinic acid will support the growth of rats on a niacin-free diet (7). One Neurospora mutant accumulates quinolinate and another mutant uses it, although somewhat less effectively than niacin (7). It has also been found that isotopically labeled quinolinic acid leads to labeled N-methylnicotinamide in the rat (8) and finally, that quinolinic acid replaced nicotinic acid for growth by Xunthomonas pruni (9). In previous work with the chick embryo, Schweigert et al. (10) found that tryptophan injections stimulated niacin synthesis. Denton et al. (11) later confirmed this, but could find no conversion of 3-hydroxyanthranilic acid to nicotinic acid. Quagliarello and Della Pietra (12) found little conversion of 3-hydroxyanthranilic acid to niacin in vitro in homogenized chick embryo; however, their preparations failed to form nicotinic acid from quinolinic acid, although the latter was present in normal developing embryos (13). Jackson et al. (14) injected tryptophan3-Cl4 into chick embryos and isolated radioactive niacin, but their data did not permit the calculation of yield and dilution. The present study was made to establish the tryptophan-toniacin pathway in the developing embryo and especially to answer the question of the role of quinolinic acid as an intermediate. It was demonstrated that radioactive isotopes from quinolinic acid-H3, 3-hydroxyanthranilic acid-H3, and tryptophan-7a-Cl4 were incorporated into nicotinic and quinolinic acids.