NICOTINIC ACID (NIACIN) 



It was prepared from N^-methylnicotinamide by the quinine-oxidising 

 enzyme of rabbit liver,^^ and synthesised by treatment of N^-methyl- 

 3-carboxy-6-pyridone (prepared by oxidising trigonelline with alkaline 

 ferricyanide or by ring closure of coumalic acid with methylamine) with 

 thionyl chloride and ammonia. ^^ Methylation and oxidation of nico- 

 tinamide gave the isomer, N^-methyl-2-pyridone-3-carboxylamide.2i« 



Another metabolite was isolated from dried chick droppings by 

 W. J. Dann and J. W. Huff 22 and identified as dinicotinyl ornithine : 



COOH 



/\ CO . NH . (CHj), . CH . NH • CO/\ 



. 11 { 



V ^N 



Thus the metabolism of nicotinic acid and nicotinamide is extremely 

 complex, and the early results reported in the literature may be mis- 

 leading, as they do not take into account all the substances into 

 which nicotinic acid may be converted. 



Excretion of Nicotinic Acid and its Metabolities in Urine 



A true picture of the fate of nicotinic acid in the body was only 

 obtained when the excretion of N^-methylnicotinamide was taken 

 into account. The method used for estimating trigonelline, involving 

 hydrolysis to nicotinic acid with strong alkali, also converts N^- 

 methylnicotinamide into nicotinic acid, so that any Fg present would, 

 in the earlier studies, have been included in the values reported for 

 trigonelline.23 when 200 mg. of N^-methylnicotinamide were given 

 orally to a normal adult, 55 mg. of Fg and 85 mg. of trigonelline were 

 excreted within forty-eight hours, so that the organism is evidently 

 capable of effecting the transformation of the amide into the betaine. 



Hochberg et al^^ found that the urinary output of N^-methyl- 

 nicotinamide on a diet yielding 23 mg. of nicotinic acid per day was 

 3 to 8 mg. daily, and that when this was supplemented with 50 to 

 200 mg. of nicotinamide, the excretion increased by an amoimt equiv- 

 alent to about 20 % of the test dose over a twenty-four hour period ; 

 one-third of this was eliminated in the first four hours. On the other 

 hand, O. Mickelsen and L. L. Erickson ^^ found that the amounts of 

 N^-methylnicotinamide excreted by normal subjects differed but 

 little with diets providing from 0-12 to 22-4 mg. of nicotinic acid 

 daily, so that merely measuring the excretion of N^- methylnicotinamide 

 resulting from an unsupplemented diet could give no useful informa- 

 tion as to the state of nicotinic acid nutrition. Johnson et al^^ how- 

 ever, found that 94 % of the nicotinic acid derivatives excreted in 



256 



