30 CHOLINE 



the aminoethanol and choline isolated from the respective phospholipids. ^^o 

 The data indicated that choline was formed from the precursor without 

 hindrance even though the diet was sufficiently low in sources of methyl 

 to cause deposition of extra liver fat. It is reasonable to accept this finding 

 as evidence of the conversion of aminoethanol to choline, but it does not 

 distinguish between methylation by transmethylation and methylation 

 by formate-to-methyl synthesis. The latter type of synthesis of choline 

 has been reported by Steensholt^^'' ^^^'^ and by Barrenscheen and 

 Skudrzyk^^^*^ in experiments in which various tissue preparations were 

 incubated with aminoethanol and either methionine or methionine sulf- 

 oxide. Steensholt also concluded that D-methionine is a more efficient 

 methyl donor than the natural isomer. ^^''^ According to Veitch and Zweig,^-^'= 

 caution is needed in the interpretation of tissue experiments in which 

 evidence of the synthesis of choline by transmethylation consists of a 

 decrease in the methionine content of the medium or in the appearance of 

 an otherwise unidentified reineckate. These workers noted that a D-amino 

 acid oxidase in the tissues used by Steensholt and by Barrenscheen de- 

 creased the level of methionine during the incubation period without 

 formation of choline. They showed, in addition that a reineckate of amino- 

 ethanol was actually formed under the conditions'^^^ in which choline 

 reineckate was presumed to have been isolated. 



The methylation in vivo of guanidoacetic acid (GA) by transmethylation 

 from choline and from methionine was demonstrated in rats by du Vigneaud 

 and his associates. ^^' ®^ The irreversibility of the reaction has been confirmed 

 by a number of investigators."- "^' ^-"^-^^^ The apparent inability of the ani- 

 mal organism to avoid methylation of a part of a dietary supplement of 

 GA makes it possible to use this means of decreasing available methyl 

 groups in the whole animal. ^^* 



Borsook and Dubnoff reported the in vitro formation of creatine from GA 

 and methionine by rat liver slices and noted that choline was ineffective 

 as a donor of methyl unless homocystine was provided. ^^®"^^* Adenosine- 



120 D. Stetten, Jr., /. Biol. Chem. 142, 629 (1942). 



121 G. Steensholt, Acta Physiol. Scand. 10, 333 (1945); 11, 294 (1946); 14, 340 (1947). 

 i"» G. Steensholt, Acta Physiol. Scand. 17, 276 (1949). 



"lb H. K. Barrenscheen and I. Skudrzyk, Hoppe-Seyler's Z. physiol. Chem. 284, 228 



(1949). 

 121C F. P. Veitch and G. Zweig, J. Am. Chem. Soc. 74, 1921 (1952). 



122 K. Bloch, R. Schoenheimer, and D. Rittenberg, J. Biol. Chem. 138, 155 (1941). 



123 K. Bloch and R. Schoenheimer, J. Biol. Chem. 131, 111 (1939). 



124 W. H. Griffith and D. J. Mulford, J. Am. Chem. Soc. 63, 929 (1941). 

 126 D. Stetten, Jr., and G. F. Grail, /. Biol. Chem. 144, 175 (1942). 



126 H. Borsook and J. W. Dubnoff, /. Biol. Chem. 132, 559 (1940). 



127 H. Borsook, /. Biol. Chem. 134, 635 (1940). 



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



