76 CHOLINE 



made equivalent to the alcohol intake by isocaloric amounts of sucrose. It 

 was concluded that the effect of alcohol on the livers of rats in experiments 

 of this type was due to a deficiency of lipotropic factors, especially of 

 choline. 



Kaufman et al. were unable to produce experimental hemochromatosis in 

 rats by feeding a diet low in lipotropic factors and containing a moderately 

 toxic level of copper. ^'^^ The combination of copper and choline in this diet 

 decreased the body weight of the animals. 



3. Effect of Sulfur Amino Acids 



In 1935, Best and Huntsman reported that casein exhibited lipotropic 

 activity,^^ a result confirmed by Channon and Wilkinson^'^'* and extended 

 to egg white and beef protein, but not to gelatin, by Best et al}'^^ In a sur- 

 vey of the effect of various amino acids, Beeston and Channon found one, 

 cystine, with a marked antilipotropic activity. ^-^ In subsequent experiments, 

 negative results for most of the other amino acids were confirmed,^" • ^-^ and 

 cysteine and homocystine were found to resemble cystine in augmenting 

 the deposition of fat in the livers of rats fed the low choline, 5 % protein, 

 and 40% fat diets that were commonly used.^-^' ^^^ The explanation of the 

 puzzling lipotropic character of many proteins was indicated l>y the im- 

 portant observation of Tucker and Eckstein that a supplement of methio- 

 nine reduced markedly the liver fat of rats on the experimental diets and, 

 in this respect, acted oppositely to cystine. ^^^ The choline-like property of 

 methionine has been confirmed repeatedly."- i^'-iss j^ jg pertinent that Best 

 called attention to the significant fact that methionine rarely reduced the 

 level of liver lipids to normal values even though it was highly effective 

 in preventing excessively fatty livers. ^^- The participation of methionine in 

 transmethylation as a methyl donor with synthesis or sparing, at least, of 

 choline offers a reasonable explanation of the lipotropic property (Section 



123 N. Kaufman, J. A. Cartaya, P. L. White, D. M. Hegsted, and T. D. Kinney, J . 



Nutrition ^f^, 433 (1952). 

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

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

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

 2^ S. A. Singal and H. C. Eckstein, J. Biol. Chem. 140, 27 (1941). 

 28 A. W. Beeston and A. P. Phitt, /. Soc. Chem. Ind. 56, 292 (1937). 

 28 S. A. Singal and H. C. Eckstein, Proc. Soc. Exptl. Biol. Med. 41, 512 (1939). 



30 H. J. Channon, M. C. Manifold, and A. P. Piatt, J. Soc. Chem. Ind. 57, 600 (1938). 



31 H. F. Tucker and H. C. Eckstein, J. Biol. Chem. 121, 479 (1937). 



32 C. H. Best and J. H. Ridout, J. Physiol. {London) 97, 489 (1940). 



33 W. H. Griffith and N. J. Wade, J. Biol. Chem. 132, 627 (1940). 



34 C. R. Treadwell, /. Biol. Chem. 176, 1141 (1948). 



35 J. M. R. Beveridge, C. C. Lucas, and M. K. O'Grady, J. Biol. Chem. 160, 505 

 (1945). 



