358 THE BIOCHEMISTRY OF B VITAMINS 



on this point. Thus, in the dog earlier reports stated that there was no 

 free nicotinic acid or nicotinamide in the urine, 12T whereas later workers 

 report its presence. 128 It has similarly been stated that birds excrete 

 only nicotinic acid, 129 although this seems unlikely, and indeed they 

 have been shown to excrete dinicotinylornithine in their droppings 

 (chicks) , 130 



It has long been known that when pyridine is administered to animals, 

 it is excreted in the form of N'-methylpyridinium ions, 131 and hetero- 

 cyclic nitrogen compounds in general seem to be largely methylated 

 prior to excretion by both plants and animals. Even before the role of 

 nicotinic acid as a vitamin was known, it had been shown that this sub- 

 stance, when administered to dogs, was excreted as trigonellin (and 

 nicotinic acid), 128 and it might be anticipated that trigonellin would be 

 a major metabolic product of niacin. Despite the fact that the dog ex- 

 cretes nearly all of a 100-mg dose of nicotinic acid as trigonellin and 

 nicotinic acid, rabbits do not excrete trigonellin, 128 and apparently can- 

 not methylate niacin. While humans excrete some trigonellin, it is now 

 believed that this is all exogenous, and the result only of the trigonellin 

 ingested. Oral administration of trigonellin to humans does not result in 

 significantly increased excretion of other nicotinic acid metabolites, but 

 does result in almost complete excretion of the entire dose as trigonel- 

 lin. 132-136 Although trigonellin is apparently ineffective in curing niacin 

 deficiency in at least some species, generalizations are dangerous since, 

 as in the case of other metabolites to be considered, results may vary 

 depending upon the magnitude of the dosage and the nutritional state 

 of the animal. At present it would seem best to believe that whereas in 

 some species (e.g., the dog) trigonellin may be a major end product of 

 niacin metabolism, it is probably found in only very small amounts in 

 many others. While there is apparently little tendency to amidate trig- 

 onellin in animals, since ingested trigonellin is largely excreted as such, 

 trigonellin in the dog may result from deamidation of N'-methylnico- 

 tinamide. This may well be the case in view of the ability of all animals 

 studied to methylate nicotinamide, and the relatively lower levels of free 

 nicotinic acid available to the dog for conversion directly to trigonellin. 

 We may well assume for the present, therefore, that trigonellin arises 

 as a product of methylated nicotinamide, and that animals that do not 

 excrete measurable trigonellin lack the tendency to deamidate F 2 . 



N'-methylnicotinamide (F 2 ) is apparently one of the major metabolic 

 products of nicotinic acid in all the animals so far studied in this regard 

 (man, 87 rat, 81 horse, 83 calf , 8G pig 84 ) . It is said to account for 94 per cent 

 of the total nicotinic acid and its metabolites found in the urine. 23 When 

 rats are fed large amounts of niacin in which the acid group is labelled 



