356 THE BIOCHEMISTRY OF B VITAMINS 



Kynurenic acid (4-hydroxyquinaldic acid) was the earliest known 

 product of tryptophan metabolism in the higher animals, 108 and it is 

 known that the liver is one of the principal sites of its formation. Only 

 the L-form of tryptophan is active in its formation, and 3-indole-pyruvic 

 acid and kynurenine are equally as active as tryptophan in kynurenic 

 acid formation. 109 In the rabbit, which normally excretes only kynurenic 

 acid, thiamine deficiency produces a simultaneous excretion of kynurenine, 

 so that thiamine presumably catalyzes the conversion of kynurenine to 

 kynurenic acid. 110 Kynurenic acid will not substitute for tryptophan in 

 the diet. Work with methylkynurenic acid and methyltryptophan deriva- 

 tives in the rabbit further indicates that it is the a-amino nitrogen atom 

 of the tryptophan that ends up in the kynurenic acid structure, rather 

 than the pyrrole nitrogen. 111 The presence in urine of two other products, 

 xanthurenine (3-hydroxykynurenine) and xanthurenic acid (4,8-di- 

 hydroxyquinaldic acid) 112, 113 has been recognized more recently. As pre- 

 viously stated, the occurrence of the yellow xanthurenic acid in the urine of 

 various species (rice moth larvae, 114 mice, 115 rats, 116 - 117 rabbits, 118 

 dogs, 118 swine, 119 ) made vitamin B 6 deficient by depletion diets or by an 

 inhibitor, 4-desoxypyridoxine, 120 is closely associated in some manner 

 with the pathway of niacin synthesis, and is the only certain intermediate 

 point so far found that can be studied in animals. The general interpre- 

 tation of this fact is that vitamin B 6 normally mediates tryptophan 

 metabolism so as to prevent (or limit) 121 its oxidation to xanthurenic 

 acid. A quinine oxidase, recently isolated, has the property of oxidizing 

 the carbon atom next to the nitrogen atom in a large variety of hetero- 

 cyclic compounds. 122 Although this enzyme is involved in niacin break- 

 down, as we shall see shortly, it does not affect tryptophan, xanthurenic 

 acid, or kynurenic acid, and is thus probably not involved in niacin 

 synthesis. It does oxidize indole, but neither indole, 3-indoleacetic acid, 

 nor anthranilic acid is effective in niacin synthesis. 123 Thus, in summary, 

 whereas there is considerable direct and indirect evidence concerning the 

 general pathway of niacin synthesis in animals, there is little certainty 

 as to the actual steps involved, and the problem remains as one of the 

 outstanding ones to be worked out in the future. 



Products of Nicotinic Acid. There is probably more evidence bearing 

 upon the nature of the products formed from nicotinic acid in animals 

 than upon the metabolism of all of the other B vitamins combined. This 

 is largely because these products are diverse in nature and occur in rela- 

 tively large amounts. Further, because of their diversity, they have com- 

 plicated the study of nicotinic acid requirements by means of the urinary 

 excretion methods, which have been so successful in other cases. It is 



