88 BIOCHIMlCA ET BIOPHYSICA ACTA VOL. 12 (1953) 



EFFECT OF THE PRESENCE OF LABILE METHYL GROUPS IN THE 

 DIET ON LABILE METHYL NEOGENESIS 



by 



VINCENT DU VIGNEAUD, JOHN M. KINNEY, JOHN E. WILSON 



AND JULIAN R. RACHELE 

 Department of Biochemistry, Cornell University Medical College, New York {U.S.A.) 



Tissue slice experiments employing i'*C-labelled precursors'"^ and experiments with 

 germ-free animals receiving deuterium-labelled drinking water^'^ have demonstrated 

 that "biologically labile" methyl groups are synthesized in the tissues of the rat. 



In the latter experiments the deuterium concentration of the body water of both 

 germ-free and nonsterile animals was maintained at about 3 atom per cent. After a 

 period of approximately 3 weeks the choline was isolated from the tissues of these rats 

 and the deuterium concentration of the trimethylamine chloroplatinate prepared from 

 the isolated choline was determined. The level of deuterium in the methyl groups of the 

 choline of these animals was between 6.4 and 9.6% of that in the body water. These 

 values agreed closely with the levels obtained in a much earlier experiment in which 

 ordinary animals were given deuterium-labelled drinking water^. 



In interpreting these results it was reasoned that if synthesis of the labile methyl 

 group did occur from some precursor in the presence of DgO, then the methyl group so 

 formed would have deuterium introduced into it during the synthetic process. From 

 our previous experience that deuterium attached to the carbon of the 'labile methyl 

 group did not exchange appreciably with the hydrogens of the body water'~^, it appeared 

 highly unlikely that in such experiments a direct exchange between the hydrogens of 

 the methyl group and the deuterium of the D2O in the body water had taken place to 

 bring about the appearance of deuterium in the methyl group. Thus, the finding of 

 deuterium in the methyl groups of choline under these conditions justified the conclusion 

 that synthesis of the methyl group must have occurred. 



In all of this work on the uptake of deuterium, the diet of the animals contained 

 labile methyl groups, so that synthesis was apparently occurring to the extent observed, 

 even in the presence of a dietary source of labile methyl groups. If the interpretation 

 were correct that the appearance of deuterium in the labile methyl groups of the body 

 is a reflection of the degree of neogenesis of methyl groups, then the appearance of a 

 larger amount of deuterium in the methyl groups of choline should result under dietary 

 conditions in which the animal was forced to synthesize its entire supply of labile methyl 

 groups. The present paper reports a set of experiments designed to test whether this was 

 the case. The amount of incorporation of deuterium from body water into the labile 

 methyl group in animals receiving dietary methyl groups was compared with that in 



References p. 91. 



