526 NIACIN 



Neurospora.^'"' ^^ It has also been shown by Yanofsky and Bonner^"* that 

 kynurenine is converted into nicotinic acid. 3-Hydroxykynurenine probably 

 is an intermediate between kynurenine and 3-hydroxyanthranilic acid.^"' ^^ 

 The exact steps between 3-hydroxyanthranilic acid and nicotinic acid are 

 still uncertain. It has been suggested^^' ^^ that the benzene ring of 3-hy- 

 droxyanthranilic acid is oxidatively cleaved in the 3-4 position to yield 

 an intermediate similar to that shown in Fig. 10. This compound might 

 then undergo ring closure with the amino nitrogen to give quinolinic acid 

 which is in turn decarboxylated to nicotinic acid,^^ or this hypothetical 

 intermediate might be decarboxylated prior to ring closure to yield nico- 

 tinic acid directly,^^ Leifer ei al.^'- have suggested that a symmetrical diamino 

 compound may be the intermediate between 3-hydroxyanthranilic acid and 

 nicotinic acid, although the evidence supporting this theory has been ques- 

 tioned.^* The details of the evidence for the various steps in the conversion 

 of tryptophan to nicotinic acid in Neurospora have been carefully reviewed 

 by Bonner and Yanofsky. ^^ 



b. Biosynthesis from Tryptophan in Mammals 



The pathway by which tryptophan is converted to nicotinic acid in mam- 

 mals is not as fully known as in Neurospora. Current information suggests 

 that it may proceed substantially as shown in Fig. 10; however, the evi- 

 dence is faulty, incomplete, and contradictory in some respects. Tryptophan 

 is known to be converted into kynurenine and kynurenic acid in several 

 animal species as first shown by Kotake^" and later proved in isotope tracer 

 experiments by Heidelberger et al.^^'^^ However, kynurenic acid is inactive 

 as a substitute for nicotinic acid in rats, and the reports on kynurenine are 

 contradictory (see Table XII). Rosen et al?^ and Krehl et alP found kynu- 

 renine inactive w^hen given in the diet or by injection, whereas Kallio and 

 Berg" and Wiss et alP reported that it would increase the urinary excretion 



62 E. Leifer, W. H. Langham, J. F. Nye, and H. K. Mitchell, J. Biol. Chem. 184, 589 

 (1950). 



63 C. Yanofsky and D. M. Bonner, J. Biol. Chem. 190, 211 (1951). 



" C. Yanofsky and D. M. Bonner, Proc. Natl. Acad. Sci. U. S. 36, 167 (1950). 



65 F. A. Haskins and H. K. Mitchell, Proc. Natl. Acad. Sci. U. S. 35, 500 (1949). 



66 L. M. Henderson, J. Biol. Chem. 178, 1005 (1949). 



67 D. M. Bonner and C. Yanofsky, Proc. Natl. Acad. Sci. U. S. 35, 576 (1949). 



68 L. M. Henderson, J. Biol. Chem. 181, 677 (1949). 



69 D. M. Bonner and C. Yanofsky, J. Nutrition 44, 603 (1951). 



ifOY. Kotake and J. Iwao, Hoppe-Seijler's Z. physiol. Chem.. 195, 139 (1931); Y. 



Kotake, J. Japan. Biochem. Soc. 21, 155 (1949). 

 " F. Rosen, J. W. Huff, and W. A. Ferlzweig, J. Nutrition 33, 561 (1947). 

 " W. A. Krehl, D. Bonner, and C. Yanofsky, J. Nutrition 41, 159 (1950). 

 " O. Wiss, G. Viollier, and M. Muller, Helv. Physiol, et Pharmacol. Acta 7, C64 



(1949). 



