Studies on the metabolism of nicotinic acid in rabbits.

Several compounds have been described as metabolites of nicotinic acid and nicotinamide in mammals. These are nicotinic acid (I), nicotinamide (2)) nicotinuric acid (2)) trigonelline (2)) W-methylnicotinamide (NMN) (3-6)) and 1-methyl-3-carboxylamide-6-pyridone (7, 8). According to the observations of various workers mammals may be divided into two groups in so far as the metabolism of nicotinic acid is concerned: mammals which aminate nicotinic acid, such as man, the dog, cat, and rat, and mammals which deaminate nicotinamide to nicotinic acid, such as the rabbit and guinea pig. The mechanism of amination and methylation of nicotinic acid and the sites where these reactions take place have been elucidated by Perlzweig, Bernheim, and Bernheim (9) and by Ellinger (10, 11). Ellinger and Abdel Kader (12) have observed that rabbits normally eliminate only nicotinic acid. Extra dietary nicotinamide and diethylnicotinamide have been found to be deaminated to nicotinic acid, which is subsequently methylated to trigonelline. An increased excretion of trigonelline by rabbits after administration of nicotinic acid has also been observed by these workers. Komori and Sendju (l), however, showed that after feeding nicotinic acid to rabbits nicotinic acid and nicotinuric acid were excreted in the urine, but no trigonelline was found. Huff and Perlzweig (4) also showed that rabbits were urlable to methylate nicotinic acid. Perlzweig, Rosen, Pearson, Peck, and Parks (13) observed that rabbits fed a supplement of nicotinamide excreted nicotinuric acid. Ellinger and Abdel Kader (12), however, did not find any nicotinuric acid in rabbit urine either before or after administration of nicotinic acid. They observed that rabbits did not eliminate NMN in the urine, even after injection of a large dose of nicotinic acid. Handler (14) could not detect NMN in the urine of rabbits fed nicotinic acid. Holman and de Lange (15) are of opinion that, although nicotinic acid is not methylated directly in the body, methylated nicotinic acid (trigonelline) can be oxidized to a pyridone. Perlzweig et al. (13) observed that rabbits excreted less than 4 per cent of a total dose of nicotinamide as NMN and its pyridone. This indicated that NMN is not a normal metabolite of nicotinic acid in rabbits. From the r&urn6 cited