354 THE BIOCHEMISTRY OF B VITAMINS 



even in Neurospora the exact sequence is not as yet well understood. 

 While there is much reason to believe that the process is similar in the 

 higher animals, there is not at present sufficient evidence to indicate that 

 this is unequivocably so. 



The primary indications that tryptophan is converted to nicotinic acid 

 in animals are the facts that the administration of tryptophan to the 

 rat, sl horse, 83 pig, 84 dog, 85 calf, 86 and humans, 87 results in the excretion 

 of increased amounts of nicotinic acid metabolites in the urine, 88 and 

 that tryptophan supplants niacin in preventing a niacin deficiency in the 

 rat, 89 chick, 90 mouse, 91 dog, 85 pig, 84 guinea pig, 82 rabbit 92 and humans. 93 

 While many authorities have attempted to explain these facts on the 

 basis of intestinal bacterial synthesis, a number of ingenious experiments 

 have largely eliminated this possibility. Thus the injection of chick eggs 

 with tryptophan causes an increase in niacin content. 95 In addition, a 

 variety of measures designed to lower or minimize the effects of intestinal 

 symbiants have been without effect upon the conversion. 96 Perhaps the 

 only known exceptions to this fact in the animal kingdom are the cases of 

 germ-free Drosophila — which require both tryptophan and niacin, and in 

 which tryptophan, when increased, causes a higher niacin requirement 97 

 and Tetrahymena. 98 It is also known that 3-pyridylmethylketone, a 

 structural analogue of niacin, is toxic to mice. 99 Since nicotinic acid pre- 

 vents its toxicity, the analogue presumably interferes with niacin forma- 

 tion, and since tryptophan similarly reverses the toxicity, it presumably 

 functions as a niacin precursor. 



The balance of the data bearing on the problem center around the fact 

 that in vitamin B (i deficiency there is a decrease in urinary kynurenic acid 

 and an increase in urinary xanthurenic acid, and that simultaneously 

 there is a decrease in nicotinic acid metabolites in the urine. 100 Since 

 kynurenic acid is known to be derived from tryptophan, 101 and kynurenine 

 is a known intermediate in niacin synthesis from tryptophan in Neuros- 

 pora, it seems logical to suppose that vitamin B 6 is involved somewhere 

 in the intermediate process. Actually, however, kynurenine does not lead 

 to increased nicotinic acid synthesis in the rat, as indicated by the 

 N'-methylnicotinamide excretion studies, and kynurenine does not pro- 

 duce growth in the rat in the absence of tryptophan and niacin. 102-104 

 3-Hydroxy-anthranilic acid does bring about increased growth and in- 

 creased niacin and F 2 excretion in rats, however. 105 Since, however, the 

 experimental basis for these reports was limited, and the work is not as 

 yet confirmed, it seems best at present to leave the subject of the involve- 

 ment of kynurenine in animal metabolism open while considering the 

 known facts regarding this general metabolic pathway. 



