METABOLISM 



or diethylnicotinamide, but in this instance methionine appeared to 

 have no effect on the methylation.'** 



Conversion of Tryptophan into Nicotinic Acid and its Metabolites 



Another important factor that has to be borne in mind in attempt- 

 ing to assess the nicotinic acid status of any individual is the possi- 

 bility that the administration of other substances besides nicotinic 

 acid may result in an increased excretion of N^-methylnicotinamide. 

 Tryptophan is of particular importance in this respect for, as already 

 stated (page 241), the rat, pig, horse, cotton-rat, chick and turkey 

 are able to convert dietary tryptophan into nicotinic acid.'*^~*^ Clearly 

 therefore, different N^-methylnicotinamide excretions would be ex- 

 pected to occur on diets that differ markedly in the amount of trypto- 

 phan present. 



Such variations were in fact found by Rosen et al.,^^ who showed 

 that the amount of nicotinic acid excreted by rats dropped immedi- 

 ately when the casein in the diet was replaced by gelatine, which 

 contains much less tryptophan. The addition of tryptophan led to a 

 large increase in the excretion of nicotinic acid and N^-methylnicotin- 

 amide ; the amount of nicotinic acid was so large, in fact, that it 

 exceeded the capacity of the animals to methylate it. Similarly. 

 P. Ellinger ^^ observed a fall in the urinary N^-methylnicotinamide 

 when rats were fed on a maize diet instead of a diet containing wheat 

 and oats. As already mentioned, wheat and oats contain much more 

 tryptophan than does maize. WTien nicotinamide was given to the 

 animals, followed by the injection of a mixture of chloroform and 

 carbon tetrachloride, which causes liver damage, the excretion of 

 N^-methylnicotinamide first increased and then fell markedly. 



Similar observations were made by H. P. Sarett and G. A. Gold- 

 smith ^0 and Perlzweig et al.^^ with human subjects, the urinary ex- 

 cretion of N^-methylnicotinamide increasing on administration of 

 L- or DL-tryptophan. 



Horses behave rather differently from other animals in that on a 

 normal diet they excrete only small amounts of N^-methylnicotin- 

 amide although, rather paradoxically, on a diet containing only o-i 

 mg. of nicotinic acid per kg., they excreted N^-methylnicotinamide 

 and no nicotinamide, nicotinuric acid or glycuronide.^^ However, 

 the oral ingestion of 2 g. of nicotinic acid daily led to the excretion of 

 18 to 54 % of unchanged acid together with a little nicotinuric acid, 

 and the oral administration or subcutaneous injection of nicotinamide 

 resulted in the excretion of 5 % of unchanged amide, the remainder 

 being unaccounted for. No increase in the excretion of trigonelline 

 or N^-methylnicotinamide resulted from administration of either 

 nicotinic acid or the amide. 



261 



