VI. BIOGENESIS 529 



may well be a side product Avhich is normally excreted into the urine rather 

 rapidly after it is formed. 



The conversion of tryptophan to nicotinic acid is a rather inefficient 

 process at best. Krehl et alP list the relative activities of tryptophan, 3- 

 hydroxyanthranilic acid, quinolinic acid, and nicotinic acid as 10, 10, 20 

 to 40, and 0.2 mg., respectively, in correcting nicotinic acid deficiency in 

 the rat. On an equimolar basis 3-hydroxyanthranilic acid is somewhat less 

 active than tryptophan, which might be explainable if the liver converted 

 a considerable portion of the 3-hydroxyanthranilic acid to quinolinic acid 

 which was then promptly excreted and thus lost to the nicotinic acid econ- 

 omy of the tissues. 



Recent evidence by Schayer and Henderson^^ using doubly labeled tryp- 

 tophan makes it very likely that the intermediate between 3-hydroxy- 

 anthranilic acid and quinolinic acid is a substance in which the benzene 

 ring is split in the 3-4 position similar to that depicted in Fig. 10. 



C. SITE OF BIOSYNTHESIS 



There have been two principal schools of thought on this subject, one 

 holding that the principal site of the tryptophan to nicotinic acid conver- 

 sion is in the tissues and the other holding that the intestinal bacteria are 

 the predominant factor in this conversion. 



1. Synthesis in Tissues 



In the rat it has been clearly demonstrated that the conversion of tryp- 

 tophan to nicotinic acid can proceed with normal efficiency without the 

 intervention of intestinal microbes. This conclusion could be inferred from 

 studies previously cited showing (1) that enzyme systems exist in tissues 

 which are capable of carrying out many of the steps in the conversion; (2) 

 that tryptophan and some of the intermediates in the conversion are effec- 

 tively changed into nicotinic acid when given parenterally; (3) that tryp- 

 tophan given parenterally leads to an increase in the nicotinic acid-con- 

 taining coenzymes of erythrocytes within 4 hours,^^ an effect too rapid to 

 be explainable if tryptophan had to be excreted into the intestinal tract, 

 converted to nicotinic acid, reabsorbed, and then picked up and incor- 

 porated into coenzymes by the erythrocytes; and (4) that a deficiency of 

 pyridoxine interfered in the conversion of tryptophan to nicotinic acid or 

 inhibited certain steps in this process in intact animals and in tissue prepa- 

 rations.''^' 71. 84, 87-94 Finally, it was shown by Henderson and Hankes^^ and 



86 R. W. Schayer and L. M. Henderson, J. Biol. Chem. 195, 657 (1952). 

 " B. S. Schweigert and P. B. Pearson, /. Biol. Chem. 168, 555 (1947). 



88 G. H. Bell, B. T. Scheer, and li. J. Deuel, Jr., /. Nutrition 35, 239 (1948). 



89 P. B. Junqueira and B. S. Schweigert, J. Biol. Chem. 174, 605 (1948). 



