610 THE BIOCHEMISTRY OF B VITAMINS 



P. americanus, P. ammonia, P. mirabilis, P. asiaticus and P. nocutarnum 

 were found to have essentially the specificity as indicated in Table 23 for 

 Proteus, with the exception of quinolinic acid, which was inactive at the 

 concentration employed. 42 



After injection into rats of compounds related to nicotinic acid, the 

 increase in urinary excretion of nicotinamide methochloride has been re- 

 ported in terms of per cent of theoretically possible increase 34 as follows: 

 nicotinic acid, 11.8; nicotinamide, 22.7; N-ethylnicotinamide, 17.2; N,N- 

 diethylnicotinamide, 16.8; N-phenylnicotinamide, 6.5; N- (4'-methyoxy- 

 phenyl) nicotinamide, 6.2; N-benzylnicotinamide, 5.8; nicotinamide 

 methochloride, 62.7; quinolinic acid, 5.2; and 3-picoline, 41.3. No increase 

 in urinary excretion of the metabolite was reported for nicotinonitrile, 

 trigonelline, or N-cyclohexylnicotinamide or related methylcyclohexyl 

 derivative. The extent to which 3-picoline is metabolized is interesting. 



Even compounds closely related to nicotinic acid are not capable of 

 replacing the vitamin. Thus, isonicotinic acid, 24 - 35, 36, 39a > 42, 43, 44 picolinic 

 acidj2 o, 24, 35, 36, 38, 39a, 42, 43, 44 dinicotinic acid, 35 - 45 cinchomeronic acid, 45 

 6-methylnicotinic acid, 24, 36, 39a - 45 2,4-dimethylpyridine-3-carboxylic 

 acid, 43 2,4,6-trimethylpyridine-3,5-dicarboxylic acid, 40 - 43 2-aminonico- 

 tinic acid, 42, 49 or pyridine betaine-3-carboxylic acid 42, 49 cannot replace 

 nicotinic acid or its amide in the nutrition of a wide variety of organisms. 

 With the exception of Staphylococcus aureus, the hexahydro derivative 

 of nicotinic acid, nipecotic acid 24, 36, 45 is not dehydrogenated. Ethyl 

 /?-oxo-3-pyridinepropionate (ethyl nicotinoacetate) 35, 45 is not cleaved by 

 some organisms, and nicotine 36, 43 is not oxidized by many organisms. 

 N-Cyclohexylnicotinamide as well as N-(2-methyl-cyclohexyl) nicotin- 

 amide cannot replace nicotinic acid in the nutrition of larvae of Tribolium 

 confusum, but the corresponding N-phenyl derivative is active. 34 Other 

 compounds which are inactive in replacing the vitamin for some organisms 

 include arecoline, 35 - 45 ^-aminopyridine, 20 - 35 > 45 N,N-diethylthionicotin- 

 amide, 38 thiopicolinamide, 38 quinoline-2-carboxylic acid, 38 quinoline-3- 

 carboxylic acid, 38 pyridine-3-sulfonic acid, 24 - 36> 43 ' 45 pyridines-sulfon- 

 amide, 38 /3-acetylpyridine, 24 - 45 benzoic acid, 35 - 49 pyridine, 24 - 40 - 45 2-pico- 

 line, 20 - 36 - 38 - 44 and 4-picoline. 44 



Of the last group, 3-acetylpyridine and pyridine-3-sulfonic acid exerted 

 a lethal toxic effect for dogs deficient in nicotinic acid, but did not exert 

 such an action on normal animals. 24 An occasional report has listed some 

 members of this group as exerting a slight stimulating effect, 38 or as 

 being capable of replacing nicotinic acid: e.g., 2,6-dimethylpyridine-3,5- 

 dicarboxylic acid and dinicotinic acid were reported to give some im- 

 provement in pellagra; 20 pyridine-3-sulfonic acid and nicotine were re- 

 ported to be active for Proteus 38 - 40 and Streptobacterium plantarum. 38 



