528 NIACIN 



which had nicotinic acid activity after acid hydrolysis. Later studies using 

 Uver homogenates and other enzyme preparations^"- ^' showed that the 

 actual compound formed in this system was quinolinic acid and that no 

 free nicotinic acid was produced. Other investigators independently re- 

 ported similar findings.^'- ^^ Neither tryptophan nor kynurenine would give 

 rise to quinolinic acid in these preparations, nor would quinolinic acid give 

 rise to nicotinic acid. However, Makino et al.^^ reported that horse and 

 cattle livers possess an enzyme system which will convert 3-hydroxyan- 

 thranilic acid to nicotinic acid, although it is difficult to be positive that 

 the end product of the reaction may not have been quinolinic acid which 

 either spontaneously or from heat and chemical treatment decarboxylated 

 to nicotinic acid and so reacted in their chemical assay procedures. Hurt 

 et al}'^ also reported that rat liver slices would convert tryptophan to nico- 

 tinic acid, although actually their procedure for determining nicotinic acid 

 would not permit them to distinguish between nicotinic acid and quinolinic 

 acid. Makino et alP also reported that their enzyme preparation converted 

 3 , 4-dihydroxyanthranilic acid to nicotinic acid just as effectively as it did 

 3-hydroxyanthranilic acid, indicating that this substance may be an inter- 

 mediate in the conversion. Their system also formed small amounts of 

 nicotinic acid from tryptophan and from quinolinic acid. Henderson d al.^^ 

 were unable to confirm these findings with 3 , 4-dihydroxyanthranilic acid 

 using rat and hog liver preparations. 



The intermediate between 3-hydroxyanthranilic acid and nicotinic acid 

 is not entirely clear, although considerable evidence indicates that quino- 

 linic acid is either an intermediate or a by-product of the reaction. Singal 

 et al}'~ were the first to note that tryptophan administration in rats and in 

 dogs^^ resulted in the urinary excretion of an unidentified substance which 

 had nicotinic acid activity after acid, but not after alkaline, hydrolysis. 

 This substance was identified by Henderson^^ as quinolinic acid. This com- 

 pound can substitute for nicotinic acid in the rat (see Table XI), although 

 it is far less effective than nicotinic acid, tryptophan, or 3-hydroxyanthra- 

 nilic acid.''^ It seems clear that quinolinic acid can be used as a precursor of 

 nicotinic acid by the rat. However, the relatively large amount required 

 in comparison to the effective amounts of tryptophan, 3-hydroxyanthranilic 

 acid, and nicotinic acid induces considerable doubt that it is a normal inter- 

 mediate between 3-hydroxyanthranilic acid and nicotinic acid, although it 



8" B. S. Schweigert and M. M. Marquette, /. Biol. Chem. 181, 199 (1949). 



81 A. H. Bokman and B. S. Schweigert, J. Biol. Chem. 186, 153 (1950). 



82 L. M. Henderson and G. B. Ramasarma, J. Biol. Chem. 181, 687 (1949). 



83 K. Makino, F. Itoh, and K. Nishi, Nature 167, 115 (1951). 



8* W. W. Hurt, B. T. Scheer, and H. J. Deuel, Jr., Arch. Biochem. 21, 87 (1949). 

 8fi L. M. Henderson, H. N. Hill, R. E. Koski, and I. M. Weinstock, Proc. Soc. Exptl. 

 Biol. Med. IS, Ul (1951). 



