VI. BIOGENESIS 525 



Subsequent investigations using isotope tracer techniques have clearly 

 proved that, at least in the rat, tryptophan increases nicotinic acid synthe- 

 sis by virtue of the fact that it is converted into nicotinic acid. Heidelberger 

 and associates^^-^*^ showed that C^* from the 3 position in the indole nucleus 

 of tryptophan became the carboxyl carbon of nicotinic acid. Likewise, 

 Schayer and associates" found that N'Mn the indole nucleus of tryptophan 

 appeared as the ring nitrogen of urinary nicotinic acid derivatives. 



These findings certainly established the conversion of tryptophan to 

 nicotinic acid but did not elucidate the exact biochemical steps. Some addi- 

 tional information was gained from tracer experiments since Heidelberger 

 et al.^^-^^ and Shayer et al}'' found that C^^ in the /3 position of the side 

 chain and Hundley and Bond^^ found that C^^ from the carboxyl group of 

 trj^ptophan did not appear in nicotinic acid. It was evident from these 

 findings that the side chain of tryptophan was not used to form nicotinic 

 acid. 



a. Nicotinic Acid Biosynthesis in Neurospora 



Much of our information on the exact mechanism by which tryptophan 

 is converted to nicotinic acid came from a series of productive investiga- 

 tions using various strains of Neurospora crassa. Some of these strains, as 

 has now been shown, synthesize nicotinic acid from tryptophan in a fashion 

 quite similar to the mechanism in animals, whereas other strains have 

 gendtic blocks so that they cannot carry out certain of the biochemical 

 steps. Beadle and associates'^ first noted that a mutant strain of Neurospora 

 could use either nicotinic acid or tryptophan for growth and that kynurenine 

 was involved in this interchangeable relationship. Bonner and Beadle'^ iso- 

 lated a substance which they believed to be a precursor of nicotinic acid 

 in this organism. Mitchell and Nyc®° and Bonner" showed that this sub- 

 stance was 3-hydroxyanthranilic acid and that it could substitute for nico- 

 tinic acid. Later studies using tracer techniques have fully confirmed the 

 fact that 3-hydroxyanthranilic acid can be converted to nicotinic acid by 



" C. Heidelberger, M. E. GullV)erg, A. F. Morgan, and S. Lepkovsky, J. Biol. Chem. 



175, 473 (1948). 

 " C. Heidelberger, M. E. Gullberg, A. F. Morgan, and S. Lepkovsky, /. Biol. Chem. 



179, 143 (1949). 

 " C. Heidelberger, E. P. Abraham, and S. Lepkovsky, /. Biol. Chem. 176, 1461 



(1948). 

 " C. Heidelberger, E. P. Abraham, and S. Lepkovsky, J. Biol. Chem. 179, 151 (1949). 

 " R. W. Schayer, G. L. Foster, and D. Shemin, Federation Proc. 8, 248 (1949). 

 58 G. W. Beadle, H. K. Mitchell, and J. F. Nj^c, Proc. Natl. Acad. Sci. U. S. 33, 155 



(1947). 

 "D. Bonner and G. W. Beadle, Arch. Biochem. 11, 319 (1946). 

 6" H. K. Mitchell and J. F. Nye, Proc. Natl. Acad. Sci. U. S. 34, 1 (1948). 

 " D. Bonner, Proc. Natl. Acad. Sci. U. S. 34, 5 (1948). 



