IV. BIOCHEMICAL SYSTEMS 41 



The series of reactions pictured in Fig. 1 indicates that only one methyl 

 of betaine takes part in true transmethylation, the remaining two being con- 

 verted to formate. Needless to say, the nitrogen is no longer quaternary 

 after the first demethylation. High radioactivity in the /3-carbon was found 

 in serine isolated from livers of rats after the administration of choline with 

 C^^-labeled methyl groups, thus demonstrating the conversion of one 

 methyl, at least, to formate. ^^^ The in vitro production of formate from the 

 methyls of choline has been demonstrated by Siekevitz and Greenberg in 

 experiments in which rat liver slices were incubated with similarly labeled 

 choline. ^^ These authors concluded that the nitrogen-methyl carbons of 

 choline and the a-carbon of glycine are specific formate donors in the syn- 

 thesis of serine from glycine. 



The contrast in the roles of betaine and of dimethylglycine in trans- 

 methylation is clearly illustrated in the experiments of du Vigneaud et al. 

 in which N^^-deuteriomethyl-labeled betaine and deuteriodimethylglycine 

 were fed to rats.^* Negligible labeling of tissue choline and creatine occurred 

 in the latter instance, whereas significant labeling with deuterium did oc- 

 cur after the administration of betaine. Little of the nitrogen of betaine 

 appeared in choline and creatine, showing that there had been no direct 

 reduction of betaine to choline. Oginsky^^^ found more methionine formed 

 from homocystine and betaine by a rat liver homogenate than from homo- 

 cystine and choline. 



The degradation of monomethylglycine, or sarcosine, has been studied 

 in several laboratories. Conversion to glycine was noted by Abbot and 

 Lewis in rabbits which excreted increased amounts of hippuric acid follow- 

 ing feeding of sarcosine and benzoic acid.^^^ The failure to observe a similar 

 effect of dimethylglycine and of betaine may be due possibly to a slower 

 rate of demethylation of these substances to the monomethyl derivative. 

 Bloch and Schoenheimer observed glycine formation in rats fed N^ ^-labeled 

 sarcosine, ^^* and Handler et al. demonstrated the conversion of dimethyl- 

 glycine and of sarcosine to glycine and formaldehyde in rat liver homog- 

 enates.^^® Mackenzie isolated C^'*-formaldehyde as the dimedon derivative 

 from preparations containing rat liver homogenates or slices and labeled 

 sarcosine. ^^^ Labeled formic acid and carbon dioxide were also identified. 

 According to this worker formaldehyde from methyl carbons of betaine 

 is a normally occurring metabolite, as is sarcosine. 



The formation of serine by the addition of formate to glycine, with the 



>" W. Sakami, J. Biol. Chem. 179, 495 (1949). 



'" E. L. Oginsky, Arch. Biochem. 26, 327 (1950). 



'9^ L. D. Abbot, Jr. and H. B. Lewis, J. Biol. Chem. 131, 479 (1939). 



'95 K. Bloch and R. Schoenheimer, J. Biol. Chem. 135, 99 (1940). 



'96 P. Handler, M. L. C. Bernheim, and J. R. Klein, J. Biol. Chem. 138. 211 (1941). 



'9' C. G. Mackenzie, J. Biol. Chem. 186, 351 (1950). 



