32 CHOLINE 



Binkley and Watson^*^ observed that methylphosphate was active in the 

 formation of creatine from GA by Hver homogenates and extracts but in- 

 active in so far as growth of rats was concerned on diets containing homo- 

 cystine in place of methionine. To what extent this ambiguous finding is 

 related to the toxicity of the methylphosphate is not known. 



Trigonelline and N^-methylniacinamide may be excreted in the urine 

 following the administration of niacin and niacinamide, respectively. Con- 

 siderable species variability exists in so far as the formation and elimination 

 of these substances are concerned, and the significance of the methylations 

 is not known. Rats, but not rabbits or guinea pigs, excrete N^-methylniacin- 

 amideafter administration of niacinamide."^ Growth in rats on protein-low 

 and methyl-poor diets is affected by the amide if a sufficient quantity is fed, 

 a result doubtless explained in part by loss of methyl from the body.^^^ 

 Perlzweig ei al}'^^ demonstrated the synthesis of N^-methylniacinamide by 

 rat liver slices and noted that the process was strictly aerobic, that intact 

 cells were required, and that niacin was unaffected by the system in which 

 the amide served as a methyl acceptor. These findings were confirmed by 

 Ellinger,^"*' who noted in addition that niacin was amidated by kidney and 

 brain tissue and by liver tissue if supplementary glutamine was provided. 

 This work was extended by Cantoni,^*- who was able to show that 

 the methylation of niacinamide does occur in cell-free preparations of rat 

 liver under anaerobic conditions in the presence of methionine, magnesium 

 ions, and a source of energy-rich phosphate such as ATP. The enzyme sys- 

 tem, for which the name nicotinamide methylkinase was suggested, was 

 partially purified. 



Epinephrine represents a product of transmethylation, according to 

 Keller et al,}^^ Following the administration of C^^-methyl-labeled methio- 

 nine in rats, this substance, formed presumably by the methylation of 

 norepinephrine, was isolated from the adrenals. 



The methylations of dimethylaminoethanol, of homocysteine, of guanido- 

 acetic acid, and of niacinamide by transmethylation appear to be of two 

 types which differ on the basis of the methyl donor and according to the 

 need of energy-rich phosphate bond compounds. Apparently, the presence 

 of methyl-containing quaternary nitrogen or ternary sulfur groups is es- 

 sential, and, for such substances, transmethylation proceeds in the absence 



1" F. Binkley and J. Watson, J. Biol. Chem. 180, 971 (1949). 



»8 p. Handler, J. Biol. Chem. 154, 203 (1944). 



139 P. Handler and W. J. Dann, J. Biol. Chem. 146, 357 (1942). 



""> W. A. Perlzweig, F. Bernheim, and M. L. C. Bernheim, J. Biol. Chem. 150, 401 



(1943). 

 1" P. Ellinger, Biochem. J. 40, Proc. xxxi (1946); 42, 175 (1948). 

 i« G. L. Cantoni, J. Biol. Chem. 189, 203 (1951). 

 '« E. B. Keller, R. A. Boissonnas, and V. du Vigneaud, J Biol. Chem. 183, 627 (1950) 



I 



