IV. BIOCHEMICAL SYSTEMS 25 



category, in addition to choline and choline-containing compounds, are 

 betaine aldehyde and betaine. Betaine was observed to be lipotropic in the 

 early experiments of Best,*^ and du Vigneaud®'*' ^^' ^^ showed that it yielded 

 methyl to homocysteine to form methionine. Welch found betaine aldehyde 

 as well as betaine lipotropic in rats^^ and mice." 



The known sulfur compounds that are methyl donors in transmethyla- 

 tion are dimethylthetin, propio-|S-dimethylthetin, and active methionine. 

 The first, an analog of betaine (sulfobetaine), was first shown to be lipo- 

 tropic by Welch (cited by du Vigneaud et a/."'*' ^*), and its part in transmeth- 

 ylation was demonstrated by du Vigneaud and coworkers.'^^ Propio-|S-di- 

 methylthetin has been isolated from a marine alga, Polysiphonia fastigiata, 

 by Challenger and Simpson.^^ It supports rat growth with homocystine 

 and is, therefore, a source of methyl.^" ■ ^^ The activity of methionine as a 

 methyl donor appeared to be an exception until it was shown by Cantoni 

 that it probably is converted to a sulfonium compound prior to its de- 

 methylation. Barrenscheen^- had concluded previously that the sulfoxide 

 of methionine was the first intermediate in transmethylation. The formula 

 provisionally assigned to active methionine, S-adenosylmethionine, by Can- 

 toni, is as follows :^^ 



Adenine— ribose—S—CH,— C Ho— CH—C=0 



I I I 



CH3 NH2 0_ 



Presumably, substrate specificity is also involved because certain beta- 

 ij^gg63,84 g^j^jj ^]^g sulfur analog of choline, sulfocholine,^^ do not donate 

 methyl to homocysteine. 



It cannot be assumed that choline serves directly as a methyl donor. 

 Present evidence suggests strongly that it must be oxidized to betaine 

 first and that dimethylglycine rather than dimethylaminoethanol is a prod- 



" V. du Vigneaud, J. P. Chandler, and A. W. Moyer, J. Nutrition 19, 11 (1940). 



" V. du Vigneaud, S. Simmonds, J. P. Chandler, and M. Cohn, /. Biol Chem. 165, 



639 (1946). 

 ^6 A. D. Welch, J. Nutrition 40, 113 (1950). 



" A. D. Welch and M. S. Welch, Proc. Soc. Exptl. Biol. Med. 39, 7 (1938). 

 "" A. W. Moyer and V. du Vigneaud, J. Biol. Chem. 143, 373 (1942). 

 7s V. du Vigneaud, A. W. Moyer, and J. P. Chandler, J. Biol. Chem. 174, 477 (1948). 

 '« F. Challenger and M. I. Simpson, Biochem. J. 41, xl (1947). 

 8» G. A. Maw and V. du Vigneaud, J. Biol. Chem. 174, 381 (1948). 

 8' G. A. Maw and V. du Vigneaud, /. Biol. Chem. 176, 1037 (1948). 

 *" H. K. Barrenscheen and T. von Valy-Nagi, Hoppe-Seyler's Z. phi/siol. Chem. 283, 



91 (1948). 

 8' G. L. Cantoni, J. Am. Chem. Soc. 74, 2942 (1952). y^^^T\c A " 



8^ H. E. Carter and D. B. Melville, J. Biol. Chem. 133, 109 (1940). /cC^^^--</ 



" G. A. Maw and V. du Vigneaud, J. Biol. Chem. 176, 1029 (1948). /^X^^^^'f 



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