40 CHOLINE 



tions from riboflavin-deficient rats. These workers believe that FAD func- 

 tions in the hydrogen transport system prior to the participation of cyto- 

 chrome c. 



h. The Choline-Betaine-Glycine Relationship 



The evidence appears indisputable that choline serves as a source of 

 labile methyl by irreversible oxidation to either betaine aldehyde or to 

 betaine. Whether the aldehyde or the acid is the methyl donor is unknown, 

 although in Fig. 1 it is assumed that it is betaine which is demethylated 

 initially. If it is not, its reduction to the aldehyde must occur with great 

 rapidity. In any event, glycine is the product of the complete demethylation 

 of the choline molecule, and the di- and monomethyl derivatives of glycine 

 are logical intermediates in addition to glycine. 



Stetten administered N'^-labeled ethanolamine, choline, glycine, and 

 betaine singly to rats and later isolated the first three compounds from 

 tissues. On the basis of the extent of labeling in the isolated materials he 

 concluded that glycine and ethanolamine were intermediates between be- 

 taine and choline'*^ and that the major route of demethylation is the con- 

 version of betaine to glycine, a precursor of ethanolamine.'*^ Definite 

 evidence that choline is not demethylated was the finding of methionine 

 and labeled dimethylglycine, not dimethylaminoethanol, after incubation 

 of a rat liver homogenate containing homocysteine and N' ^-labeled 

 choline.'''^ 



The proof of the transfer of one intact methyl group, at least, from the 

 product of oxidation of choline, either betaine aldehyde or betaine, is im- 

 pressive. Following the feeding of deuteriomethyl-labeled choline to rats, 

 methionine and creatine containing deuteriomethyl groups were isolated 

 from tissues. ^^ This transmethylation occurred regardless of a dietary need 

 of methionine, indicating that the reaction was one of those characterized 

 by Schoenheimer as an "automatic and non-interruptable biochemical pro- 

 cess."'** That betaine is a source of labile methyl in the sense commonly as- 

 cribed to the choline methyl has long been known."*'' "■ '^^^ '*^' '*" Signifi- 

 cantly, betaine is not a complete replacement for choline in the chick which 

 is unable to form monomethylaminoethanol from aminoethanol. It is not 

 antiperotic, for instance, a function which appears to depend upon the in- 

 corporation of choline or of a similar molecule, such as arsenocholine, into 

 phospholipids.'^' 



186 D. Stetten, Jr., J. Biol. Chem. 138, 437 (1941). 

 >" D. Stetten, Jr., J. Biol. Chem. 140, 143 (1941). 



188 A. R. Moss and R. Schoenheimer, J. Biol. Chem. 135, 415 (1940). 



189 A. P. Piatt, Biochem. J. 33, 505 (1939). 



19" J. P. Chandler and V. du Vigneaud, J. Biol. Chem. 135, 223 (1940). 

 191 T. H. Jukes, J. Nutrition 20, 445 (1940). 



