658 VI. OCCURRENCE OF LIPIDS IN THE ANIMAL 



acid produces an extreme fattening of the liver, even when protective doses 

 of choline are being administered. The reason for the antilipotropic action 

 of this compound is that it exerts a higher priority for methyl groups than 

 does ethanolamine, with the result that methionine and also the ad- 

 ministered choline transfer their methyl groups to guanidoacetic acid to 

 form creatine. 708 - 709 Du Vigneaud et al. 6b9 demonstrated that the methyl 

 group in methionine may be used for the methylation of guanidoacetic 

 acid to form creatine, as shown in (4). 652 



NH 2 . , .. . . NH 2 



, z Methionine , 



I + CH 3 I 



C=NH > C=NH (4) 



I I 



NHCH 2 COOH N(CH 3 )CH 2 COOH 



Guanidoacetic Creatine 



acid 



Borsook and Dubnoff 710 reported that DL-homocystine plus choline accel- 

 erates the methylation of guanidoacetic acid as effectively as does DL- 

 methionine; however, homocystine is ineffective in the absence of choline, 

 just as choline is inactive without homocystine. It was found that DL- 

 homocystine is more potent than is Z)L-homocysteine. 



On the other hand, a number of common physiologic compounds other 

 than methionine, choline, and betaine, may be used to supply methyl groups 

 for transmethylation. Thus, Heppel et al. ln reported that the methyl 

 purines, caffeine, theobromine, and theophylline, exert a lipotropic action 

 when choline is absent from the diet. It is suggested that these compounds 

 may act as methylating agents under these circumstances. 



Sarcosine, (CH 3 )NHCH 2 COOH, may likewise serve as a methyl donor for 

 creatine and choline, but its effectiveness as a transmethylating agent is so 

 low that it has little influence on liver fattening. By using sarcosine con- 

 taining N 15 , du Vigneaud et al. 712 demonstrated a transfer of methyl groups 

 to choline and creatine, but the rate at which the methyl groups appeared 

 was slow as compared to that when deuteriocholine was fed. 



It is evident that the body not only possesses a limited ability to syn- 

 thesize the methyl radical but also has the power to transfer this group 

 intact from one molecule to another. The process of transferring the 



708 K. Bloch and R. Schoenheimer, /. Biol. Chem., 188, 167-194 (1941). 

 7 ° 9 H. Borsook and J. W. Dubnoff, J. Biol. Chem., 132, 559-574 (1940). 



710 H. Borsook and J. W. Dubnoff, /. Biol. Chem., 160, 635-636 (1945). 



711 L. A. Heppel, V. T. Porterfield, and E. G. Peake, Arch. Biochem., 15, 439-443 

 (1947). 



712 V. du Vigneaud, S. Simmonds, and M. Cohn, J". Biol. Chem., 166, 47-52 (1946). 



