360 THE BIOCHEMISTRY OF B VITAMINS 



tinamide and F 2 produce similar amounts of urinary F 2 , 151 and (3) that, 

 as previously mentioned, rats fed nicotinic acid in which the carbon 

 atom of the carboxylic acid group was labelled with C 13 excrete amounts 

 of labelled F 2 in the urine which indicate that all of the F 2 is derived 

 from nicotinic acid. F 2 is absent from the urine of pellagrins and its ex- 

 cretion is in general a function of the nicotinic acid and tryptophan in- 

 take of animals. 152 Wide individual variations exist, however, and some 

 individuals with an apparently adequate niacin intake do not excrete 

 any F 2 . 153 There are, moreover, apparently significant variations among 

 species in their ability to form F 2 . Thus in the horse on a low-niacin diet 

 tryptophan stimulates only slightly higher nicotinic acid excretion, and 

 no increase in F 2 excretion, 154 whereas in the cotton rat tryptophan 

 stimulates an increase in both, 155 but principally in the F 2 . 156 In humans, 

 tryptophan apparently does not affect niacin excretion, but does increase 

 the excretion of F 2 markedly. 157 About half the niacin metabolites ex- 

 creted by calves are active for Lactobacillus arabinosus, the remainder 

 being largely F 2 . 158 In vitamin B 6 deficient rats, it has previously been 

 mentioned that there is no F 2 excretion. When pyridoxine is administered 

 to these animals, there is a prompt disappearance of xanthurenic acid 

 from the urine, but only a very gradual reappearance of F 2 . 159 Therefore, 

 although F 2 may be formed rather directly from nicotinamide, it would 

 seem that such a wide variety of factors influence its formation that ex- 

 tended study will yet be required to assess its exact place in niacin 

 metabolism. 



It has been realized for some time that the level of the excretion of 

 F 2 is the result of two major factors: its synthesis from nicotinamide 

 and its conversion to still other metabolic products. 160 It has recently 

 been discovered that liver contains an enzyme capable of oxidizing 

 quinine and many other nitrogen heterocycles, the enzymatic oxidation 

 characteristically involving the conversion of the carbon atom adjacent 

 to the nitrogen into a keto group. 122, 123 This oxidase readily converts F 2 

 into N'-methyl-6-pyridone-3-carboxylamide in vitro, and it has been 

 found that the administration of 600-900 mg of nicotinamide to humans 

 results in the urinary excretion of about 100 mg of this same compound. 

 It thus appears that this substance is a major product of niacin metab- 

 olism in at least some species. To date, however, it is uncertain as to what 

 extent its presence may have influenced earlier determination of other 

 niacin metabolites. In any case it seems likely that further analogous 

 pyridones may eventually be discovered among the metabolic products 

 of niacin. 



Nicotinuric acid (nicotinylglycine) was found to be a major product 

 of niacin metabolism in the dog long before niacin was implicated as a 



