516 NIACIN 



tinic acid are formed are almost completely unknown except for the amide 

 (p. 505) and N^-methyl derivatives {vide infra). 



O. N'-METHYLATION OF NICOTINAMIDE 



Nicotinamide can be methylated in certain tissues by an aerobic process 

 analogous to the methylation of guanidoacetic acid to creatine; i.e., the 

 reaction is dependent on oxygen and is inhibited by oxidation inhibitors.^"- 

 Perlzweig and associates-"^ showed that rat liver slices, but not kidney or 

 muscle, can methylate nicotinamide and that methionine enhances the 

 reaction. This finding has been amply confirmed by others. ^^'^ Cantoni^"* 

 has now obtained a soluble enzyme system (cell-free) from rat, pig, guinea 

 pig, and dog liver which catalyzes the methylation of nicotinamide in the 

 presence of methionine, Mg++, and adenosinetriphosphate. Only L-methi- 

 onine could be used in the system. Betaine and dimethylthetin were inac- 

 tive in replacing methionine unless homocysteine was present. The system 

 would not methylate nicotinic acid. 



The methylation reaction is apparently irreversible under biological con- 

 ditions, since N^-methylnicotinamide cannot replace nicotinamide in the 

 diet. Likewise this methylated compound has no lipotrophic activity as it 

 would if it could give up its methyl group.-"^ Keller et al}^^ used a tracer 

 technique to prove that N'-methyl groups attached to nicotinamide do 

 not participate in transmethylation reactions. 



The liver can, however, degrade N'-methylnicotinamide to unknown com- 

 pounds.^"^ It is apparently a lack of this degradative reaction which accounts 

 for the paradoxical increase in urinary N^-methylnicotinamide in animals 

 and in human subjects whose hvers have been severely damaged by carbon 

 tetrachloride^"^ or phosphorus.^"^ 



Beher et alP^ have found that small doses of testosterone decrease the 

 urinary excretion of N^-methylnicotinamide, apparently because of an in- 

 creased storage of DPN and TPN in the tissues. Calvo et al?^^ found that 

 thyroidectomy or thiouracil administration decreased urinary N^-methyl- 

 nicotinamide excretion. Excretion of this compound was also decreased by 



202 Nutrition Revs. 6, 28 (1948). 



203 W. A. Perlzweig, M. L. C. Bernheim, and F. Bernheim, /. Biol. Chem. 150, 401 

 (1943). 



204 G. L. Cantoni, /. Biol. Chem. 189, 203 (1951). 



206 P. Handler and I. N. Dubin, /. Nutrition 31, 141 (1946). 



206 E. B. Keller, J. L. Wood, and V. DuVigneaud, Proc. Sac. Exptl. Biol. Med. 67, 

 182 (1948). 



207 W. A. Perlzweig, J. W. Huff, and F. Rosen, Federation Proc. 5, 149 (1946). 



208 A. Bonsignore and L. Bevilacqua, Bull. soc. ital. bid. sper. 23, 1219 (1947). 



209 W. T. Beher, E. M. Crigger, and O. H. Gaebler, /. Nutrition 47, 353 (1952). 



210 J. M. Calvo, C. C. Boehme, and J. Goemine, Bol. soc. bid. Santiago Chile 6, 88 

 (1949). 



