20 CHOLINE 



under these conditions. Best and coworkers soon noted that the effective 

 component in lecithin was chohne/""^- Betaine was also found to have 

 lipotropic activity in rats. 



The use of the rat as a test animal in place of the depancreatized dog 

 facilitated greatly the extension of the investigations that comprised the 

 first phase of the study of the role of choline as a dietary essential. During 

 the next few years the study of the relation of dietary factors to choline- 

 preventable fatty livers in rats was pursued vigorously. Best et at. noted 

 the protective action of choline in diets containing added cholesterol**' ** 

 and the protective effect of protein. ''^"^^ Channon and coworkers examined 

 the effect of protein and of amino acids.'*^'^- Following the demonstration 

 of the antilipotropic effect of dietary cystine by Beeston and Channon,^' 

 Tucker and Eckstein^* noted that supplements of methionine had an oppo- 

 site effect and were lipotropic. This similarity in the anti-fatty liver action 

 of choline and of methionine was the first observation in the second phase 

 of studies of the nutritional importance of choline, a phase that was to 

 place choline in a unique position in metabolism as a source of labile methyl 

 groups as well as a component of biochemically important tissue constitu- 

 ents. 



In 1932 Jackson and Block^'* presented the first evidence of a mammalian 

 requirement of methionine in experiments in which growi^h was improved 

 in rats by the addition of this amino acid to a diet low in sulfur amino acids. 

 In the same year Butz and du Vigneaud" prepared homocystine, a de- 

 methylated product of methionine, by the action of strong sulfuric acid on 

 methionine, and du Vigneaud et al}^ showed that homocystine supported 

 the growth of rats on a cystine-poor diet. Later, Womack et al.^'^ found that 



4« C. H. Best, J. M. Hershey, and M. E. Huntsman, Am. J. Physiol. 101, 7P (1932). 



" C. H. Best and M. E. Huntsman, J. Physiol. (London) 75, 405 (1932). 



« C. H. Best, G. C. Furguson, and J. M. Hershey, J. Physiol. (London) 79, 94 (1933). 



« C. H. Best and J. H. Ridout, J. Physiol. (London) 78, 415 (1933). 



" C. H. Best, H. J. Channon, and J. H. Ridout, J. Physiol. (London) 81, 409 (1934). 



« C. H. Best and M. E. Huntsman, J. Physiol. (London) 83, 255 (1935). 



« C. H. Best and H. J. Channon, Biochem. J. 29, 2651 (1935). 



" C. H. Best, R. Grant, and J. H. Ridout, J. Physiol. (London) 86, 337 (1936). 



« C. H. Best and J. H. Ridout, J. Physiol. (London) 87, 55P (1936). 



*9 H. J. Channon and H. Wilkinson, Biochem. J. 29, 350 (1935). 



6« A. W. Beeston, H. J. Channon, and H. Wilkinson, Biochem. J. 29, 2659 (1935). 



" A. W. Beeston and H. J. Channon, Biochem. J. 30, 280 (1936). 



^^ A. W. Beeston, H. J. Channon, J. V. Loach, and H. Wilkinson, Biochem. J. 30, 



1040 (1936). 

 " H. F. Tucker and H. C. Eckstein, /. Biol. Chem. 121, 479 (1937). 

 " R. W. Jackson and R. J. Block, /. Biol. Chem. 98, 465 (1932). 

 *s L. W. Butz and V. du Vigneaud, J. Biol. Chem. 99, 135 (1932). 

 66 V. du Vigneaud, H. M. Dyer, and J. Harman, J. Biol. Chem. 101, 719 (1933). 

 " M. Womack, K. S. Kemmerer, and W. C. Rose, J. Biol. Chem. 121, 403 (1937). 



