22 CHOLINE 



labeled methionine. Within experimental error the same ratio of C^^ to 

 deuterium was found in choline and creatine methyls as in the sulfur methyl 

 of the administered methionine. ^^ 



At the time these studies were in progress there was no reason to doubt 

 the supposed inability of the animal organism to synthesize so-called labile 

 methyl, the methyl of choline and of methionine. The ease with which 

 either choline or methionine deficiency was produced and the ease of pre- 

 vention of these deficiencies by methionine or by choline and homocystine, 

 respectively, made the concept of a dietary deficiency of labile methyl very 

 plausible. More recent findings, however, have made it necessary to revise 

 this concept. Discussions to follow indicate that the animal organism does 

 have the ability to synthesize the methyls found in choline or methionine 

 but only if the diet is otherwise adequate. Furthermore, under the best 

 circumstances the rate of the synthetic process may be limited. 



This conclusion has been reached in three types of experiments: (1) 

 diets containing homocystine but devoid of methionine and of other known 

 sources of labile methyl have supported the growth of rats;®'- ^^' ^° (2) 

 deuterium-labeled choline methyl was found in the tissues of germ-free rats 

 supplied deuterium-labeled water ;^i' " and (3) C^Mabeled choline and me- 

 thionine methyls have been found after the incubation of tissue preparations 

 with C^Mabeled formate.''^ Although there is nothing in the present evi- 

 dence that questions the reality of metabolic transfer of intact methyl 

 groups under certain conditions, it is necessary to distinguish carefully 

 between methylation due to transmethylation and methylation due to 

 synthesis of a methyl from formate. The term transmethylation Avill be 

 used for the reactions in which intact methyls participate. The general 

 designation, formate transfer, and the more descriptive terms, formate-to- 

 methyl and methyl-to-formate transfer, will be employed for those reactions 

 in which there is synthesis or degradation of a methyl group. In these 

 instances a carbon-oxygen linkage replaces the carbon-hydrogen bonding, 

 or the reverse, in addition to transfer of the carbon. 



In many instances the experimental data are insufficient to permit an 

 unequivocal differentiation between the two types of methylation. Particu- 

 larly disturbing is the difficulty in describing the series of reactions in which 

 a formate carbon becomes a labile methyl carbon. It is not possible to state 



68 E. B. Keller, J. R. Rachele, and V. du Vigneaud, /. Biol. Chem. 177, 733 (1949). 



69 M. A. Bennett, G. Medes. and G. Toennies, Growth 8, 59 (1944). 

 '0 M. A. Bennett, J. Biol. Chem. 163, 247 (1946); 187, 751 (1950). 



" V. du Vigneaud, C. Ressler, and J. R. Rachele. Science 112, 267 (1950). 



" V. du Vigneaud, C. Ressler, J. R. Rachele, J. A. Reyniers, and T. D. Lucke}^, 



J. Nutrition 45, 361 (1951). 

 " V. du Vigneaud and W. G. Verly, /. Am. Chem. Soc. 72, 1049 (1950). 



