80 CHOLINE 



therefore, a potential antagonist of the natural amino acid. It was found to 

 inhibit methyl transfer from methionine to choline l)ut not to creatine.'^'* 

 Fatty livers occurred rapidly after its injection into female rats V)ut not in 

 male rats, and this antilipotropic effect was opposed by methionine. ^^^ 

 Evidence has been provided for its incorporation in vivo into an abnormal 

 type of tissue protein. ^^® Stekol showed that ethionine was deethylated in 

 the rat^" and that its inhibitory action on rat growth was prevented by the 

 administration of either choline or methionine. ^^^ In similar experiments 

 with trie thy Icholine, choline was more efficient than methionine in the pre- 

 vention of a deleterious effect on growth. ^^^ These data suggest the partici- 

 pation and interference of ethionine in transmethylation. 



4. Effect of Other Nutrients 



A lipotropic action of inositol was first reported by Gavin and McHenry^^" 

 and studied further by MacFarland and McHenry.^*^! Rats, 90 to 100 g. in 

 weight, were depleted of fat and of B vitamins for 3 weeks on a fat-free, 

 high carbohydrate diet; during a fourth week test substances were adminis- 

 tered and the livers were analyzed for lipids. In such experiments a crude 

 beef liver fraction, a liver extract, or a biotin plus folic acid supplement with 

 extra thiamine, riboflavin, pantothenate, and nicotinic acid produced fatty 

 livers resistant to choline and responsive to inositol. McHenry emphasized 

 particularl}'- the effectiveness of inositol in reducing the level of liver choles- 

 terol. A supplementary action of inositol with choline was described by 

 EngeP^^ and confirmed by Forbes."^ Beveridge noted that the inositol effect 

 was absent if the diet contained corn oil.^^''' ^^^ The favorable influence of 

 inositol was also observed by Handler, ^^^ but both Handler^* and Best ei 

 al}^"^ reported that in the absence of choline renal lesions were intensified 



'^^ S. Simmonds, E. B. Keller, J. P. Chandler, and V. du Vigneaud, J . Biol. Chem. 



183, 191 (1950). 

 « D. Jensen, I. L. Chaikoff, and H. Tarver, J. Biol. Chem. 192, 395 (1951). 

 56 M. Levine and H. Tarver, J. Biol. Chem. 192, 835 (1951). 

 " J. A. Stekol, K. W. Weiss, and S. Weiss, J. Am. Chem. Soc. 72, 2309 (1950). 



58 J. A. Stekol and K. W. Weiss, Proc. Soc. Exptl. Biol. Med. 77, 213 (1951); /. Biol. 

 Chem. 179, 1049 (1949); 185, 577 (1950). 



59 J. A. Stekol and K. W. Weiss, J. Biol. Chem. 185, 585 (1950). 



69 G. Gavin and E. W. McHenry, J. Biol. Chem. 139, 485 (1941); 141, 619 (1941). 



61 M. L. MacFarland and E. W. McHenry, J. Biol. Chem. 159, 605 (1945); 176, 429 

 (1948). 



62 R. W. Engel, J. Nutrition 24, 175 (1942). 



63 J. C. Forbes, Proc. Soc. Exptl. Biol. Med. 54, 89 (1943). 



64 J. M. R. Beveridge, Science 99, 539 (1944). 



66 J. M. R. Beveridge and C. C. Lucas, J. Biol. Chem. 157, 311 (1945). 



66 P. Handler, J. Biol. Chem. 162, 77 (1946). 



67 C. H. Best, C. C. Lucas, J. M. Patterson, and J. H. Ridout, Science 103, 12 (1946). 



