706 THE BIOCHEMISTRY OF B VITAMINS 



Efforts to determine what specific actions of choline are responsible 

 for the gross physiological changes observed in choline deficiency led to 

 the discovery of a functional relationship between choline and methionine. 

 In 1938 Tucker and Eckstein 12 reported that methionine exerts an effect 

 on liver fat similar to that shown by choline, du Vigneaud and co-work- 

 ers 13 later observed that methionine can be replaced in the diet of rats 

 by homocysteine, provided choline or betaine is simultaneously supplied. 

 They suggested that this effect is due to the conversion of homocysteine 

 to methionine by the transfer of methyl groups from choline. 14 As a 

 result of these and subsequent investigations it is now apparent that 

 choline, betaine and methionine can serve as metabolic sources of the 

 "transferable methyl group," which may be an essential dietary con- 

 stituent. 



Choline apparently functions as the intact molecule in the synthesis of 

 some of the phospholipides which play an important role in the regula- 

 tion of fat metabolism as well as in the synthesis of acetylcholine. The 

 latter compound has attracted much attention as a "chemical transmitter" 

 of the nerve impulse. 



Specificity 



A considerable number of compounds have been tested for their ability 

 to alleviate the various symptoms produced by choline deficiencies in 

 rats and in chicks and turkey poults. The results of these tests are sum- 

 marized in Table 47. 



The ability of various compounds to permit growth of the rat or the 

 chick on a choline-methionine-free diet supplemented with homocysteine 

 has been interpreted to mean that these compounds are able to transfer 

 methyl groups to homocysteine to form methionine. This conversion has 

 been demonstrated following the administration of deuteriocholine 45 and 

 deuteriobetaine. 46 On this basis the following compounds have been found 

 to be methyl donors: choline, choline derivatives such as lecithin and 

 phosphorylcholine, monoethylcholine, betaine, dimethylthetin (sulfobe- 

 taine), methylethylthetin and dimethylpropiothetin. The minimal re- 

 quirement for methyl donor activity appears to be the presence of at least 

 one methyl group attached directly to an onium pole. That such activity 

 may also be conditioned by enzyme specificity is suggested by the fact 

 that transmethylations utilizing choline, betaine and dimethylthetin are 

 catalyzed by three different enzymes. 47 This view is further supported by 

 the observation that sulfobetaine is an active methyl donor, while sulfo- 

 choline is inactive in this respect. Moreover, dimethylpropiothetin ex- 

 hibits a marked growth-promoting activity, whereas its nitrogen analogue, 



