ii6 



INTERMEDIARY METABOLISM AND GROWTH I 



+ HCOOH 



COOH 



-C-CH— CH-COOH 



I 



CH 



NH, 



NH 



Tryptophane 



tryptophane 

 peroxidase 



O 



-C-CH,- CH-COOH 

 I 

 NHa HgO^ 



"NH formylase 



CHO Kynurenine 



Formylkynurenine 



TPNH 



Alanine 



COOH 



COOH 



OH 



3 - Hydroxykynurenine 



COOH 



Fig. 54. Metabolic pathway of conversion of tryptophane to nicotinic acid. 



mediate to qiiinolinic acid (Mehler, 1956). The significance of picolinic and quino- 

 linic acids is not as yet clear, the latter being poorly converted to nicotinic acid. It is 

 possible that under physiological conditions, the amide bond of nicotinamide is 

 formed prior to the closure of the pyridine ring. By isotope experiments, it has 

 been shown that the side chain of tryptophane is lost during the formation of 

 nicotinic acid. The [3-carbon of the indole ring becomes the carboxyl group of 

 nicotinic acid and the indole nitrogen becomes the pyridine nitrogen (Fig. 54). 

 These observations are consistent with a mechanism involving the opening of the 

 ring of 3-hydroxyanthranilic acid and cyclization of the presumed intermediate 

 aldehyde to form a pyridine ring. 



Although niacin is synthesized from tryptophane in Neiirospora and rat liver, it appears 

 that neither tryptophane nor indole function as niacin precursors, in E. coli and in B. 

 siiblilis. The niacin precursors in these bacteria are as yet unknown (Yanofsky, 1954). 



{b) Formation of DPN^ and TPJV* 



The administration of nicotinamide to mice results in a ten fold rise in the DPN^ 

 content of liver. Increases are also found in spleen, kidney, and neoplastic tissues 

 (Kaplan «^ al., 1956a). Although nicotinic acid and tryptophane also promote an 

 increase in liver DPN^, the magnitude is much smaller than that with nicotinamide. 



Erythrocytes can form DPN^ from nicotinamide and glucose in vitro. It is not 

 possible to demonstrate an increase in nicotinamide riboside or the ribotide, 

 suggesting that the conversion of the latter substances to DPN^ is very rapid; 

 however formation of nicotinamide riboside by partially purified hog liver enzyme 

 has been demonstrated (Rowen and Kornberg, 1951). 



