LIPID STORAGE UNDER ABNORMAL CONDITIONS 649 



V. The Lipotropic Action of Compounds Related to Methionine: 

 Evidence that the action of methionine is relatively specific is afforded by 

 the fact that the closely related methoxybutanoic acid is inactive. Thus, 

 methoxinine or oxymethionine, CH 3 OCH 2 CH 2 CH(NH 2 )COOH, which 

 was synthesized by Roblin et al., 6iZ was shown to have a growth-inhibitory 

 action on bacteria which was somewhat counteracted by methionine. 644 

 However, Shaffer and Critchfield 644 reported it to be lipotropic, although it 

 possessed nephrotoxic properties. 



Roberts and Eckstein 645 investigated the activity of other sulfur com- 

 pounds when included in the rations of rats on diets producing fatty livers. 

 Dimethyl sulfide, (CH 3 ) 2 S, dimethyl disulfide, CH 3 S— SCH 3 , methyl xantho- 

 S S 

 II II 



genate, CH 3 OCS— SCOCH 3 , and £-methylisothiourea, HN:C(NH 2 )SCH 3 , 

 were all found to be lipotropic when administered intraperitoneally. Al- 

 though mercaptan formation could be detected only after dimethyl disul- 

 fide was given, it was suggested that the formation of this compound might 

 likewise occur in the case of the other lipotropic sulfur compounds, and 

 that this might be the active lipotropic agent. On the other hand, sodium 





 t 

 sulfide, Na 2 S, and methionine sulfone CH 3 OSCH 2 CH 2 CH(NH 2 )COOH, 



when given intraperitoneally, and trimethylsulfonium chloride, (CH 3 ) 3 SC1, 

 when administered orally, had neither a lipotropic nor an antilipotropic 

 action. 



Jensen et al. 6i6 demonstrated that, in contradistinction to the strong lipo- 

 tropic activity of methionine, ethionine, C 2 H 5 SCH 2 CH 2 CH(NH 2 )COOH, 

 does not induce a lipotropic effect but, on the contrary, actually exhibits a 

 liver-fattening action. Choline and other lipotropic agents were found to 

 have little or no effect on this type of fatty liver. 647 Farber and associates 647 

 consider this finding to be inconsistent with the assumption that ethionine 

 produces fatty livers by blocking the demethylation of methionine. Car- 

 bohydrate in large doses was found to prevent or to cure this type of fatty 

 liver. On the other hand, Simmonds et al., 6iS employing deuterio-labeled 



643 R. O. Roblin, Jr., J. 0. Lampen, J. P. English, Q. P. Cole, and J. R. Vaughan, Jr., 

 J. Am. Chem. Soc, 67, 290-294 (1945). 



644 C. B. Shaffer and F. H. Critchfield, J. Biol. Chem., 174, 489-493 (1943). 

 646 E. Roberts and H. C. Eckstein, /. Biol. Chem., 154, 367-375 (1944). 



646 D. Jensen, I. L. Chaikoff, and H. Tarver, J. Biol. Chem., 192, 395-403 (1951). 



647 E. Farber, M. V. Simpson, and H. Tarver, J. Biol. Chem., 182, 91-99 (1950). 



648 S. Simmonds, E. B. Keller, J. P. Chandler, and V. du Vigneaud, J. Biol. Chem., 183, 

 191-195 (1950). 



