NICOTINIC ACID (NIACIN) 



N* -Methylnicotinamide 



The excretion of another metabolite of nicotinic acid was first 

 noted by Najjar and his co-workers.^ They observed that pellagrins 

 excreted in the urine a fluorescent substance designated F^, which 

 disappeared when the patients were treated with nicotinic acid, and 

 was replaced by another fluorescent substance known as F2 ; this 

 was not present in the urine of pellagrins. The administration of 

 nicotinic acid to a normal individual led to a marked increase in the 

 excretion of this second fluorescent substance, and it was suggested 

 that Fj was a precursor of Fg, into which it was converted under the 

 influence of nicotinic acid. They found that in addition to nicotinic 

 acid, nicotinamide and coramine were able to bring about this trans- 

 formation, but not trigondline, quinolinic acid or pyrazine-carboxylic 

 acids ; there was a close parallelism between the ability of substances 

 to cure pellagra and their effect on the fluorescent excretion products. 



The excretion of F^ was also observed in dogs with canine black- 

 tongue ; it was replaced by F2 when the dogs were given nicotinic acid.^® 

 Large doses of Fg were excreted by all animals capable of methylating 

 nicotinamide, and in rats, which synthesise nicotinic acid from trypto- 

 phan, the excretion of Fg ran parallel with that of trigonelline when a 

 nicotinic acid-free diet was administered. In rabbits, on the other 

 hand, which do not convert nicotinic acid into trigonelline, the ad- 

 ministration of nicotinamide was not followed by excretion of Fg.^^ 

 Fg was isolated and shown to be N^-methylnicotinamide, which was 

 synthesised by the method of Karrer et al.^^ 



CONH3 



ci- 



CH, 



Both formed a picrate, m.p. 189-5° C.^^' ^^ The substance is some- 

 times referred to as nicotinamide methochloride. It obviously bears 

 the same relationship to nicotinamide that trigonelline does to nico- 

 tinic acid. 



Nicotinamide was converted into N^-methylnicotinamide by in- 

 cubation with rat-liver slices, and the extent of the transformation was 

 increased by the addition of methionine.^* The in vivo conversion of 

 nicotinic acid into trigonelline is also brought about by methionine, 

 and these reactions compete with others that depend on the avail- 

 ability of methionine or choline (see page 601). Thus, nicotinic acid, 

 although it had no adverse effect on the growth of rats, resulted in 

 the formation of fatty livers, which were prevented by methionine, 

 choline or betaine and aggravated by cystine or homocystine. Nico- 



254 



