660 VI. OCCURRENCE OF LIPIDS IN THE ANIMAL 



groups attached to the nitrogen is a deciding factor in lipotropic action; 

 thus, the triethylhydroxyethylammonium hydroxide, or the so-called tri- 

 ethylcholine (HOCH 2 CH 2 N(C 2 H f ) 3 OH), has two-thirds of the lipotropic 

 activity of choline, weight for weight, 722,723 but the corresponding tripropyl 

 compound is practically devoid of lipotropic action. 



The presence of the quaternary nitrogen appears to be unnecessary. 

 Trimethylaminoxide, (CH 3 ) 3 NO, has been shown to play an important role 

 as a lipotropic agent. 721 It is believed that its behavior in choline trans- 

 methylation is similar to that of methionine sulf onide : 



O NH 2 



CH 3 SCH 2 CH 2 CHCOOH 



in the methyl transfer from methionine. However, the mechanism differs 

 for these two reactions. The methionine-attacking pherase is a lyoenzyme 

 which is cyanide-sensitive, while the choline pherase is a cyanide-insensitive 

 desmoenzyme. Du Vigneaud and associates 724 found that dimethylamino- 

 ethanol ((CH 3 ) 2 NCH 2 CH 2 OH) prevented fatty livers, although it was 

 decidedly inferior to choline in promoting the growth of rats on a homo- 

 cystine diet. Both the dimethyl compound and the monomethylamino- 

 ethanol (CH 3 NHCH 2 CH 2 OH) were effective precursors of choline, as dem- 

 onstrated by the transfer of deuterium-labeled methyl groups from the 

 amines to newly synthesized choline. On the other hand, dimethyl- 

 glycine ((CH 3 ) 2 NCH 2 COOH) was relatively ineffective as a precursor of 

 choline or creatine. 716 Monomethylaminoethanol was found to have a 

 high degree of toxicity. It is not a direct methyl donor. Although it is not 

 considered that either di- or monomethylaminoethanol enters directly into 

 transmethylation reactions, such as would lead to the formation of methi- 

 onine or creatine, these compounds presumably act as lipotropic agents by 

 virtue of their ready conversion to choline. 



When the alcohol group is inactivated, as for example by the formation 

 of an ether, the lipotropic activity is destroyed. 714 Welch and Welch 715 re- 

 ported that the phosphorus and arsenic analogues of choline are about one- 

 half as effective in removing fat from the liver as are the corresponding 

 choline compounds. The results are summarized in Table 23 (page 661). 



From the data presented in Table 23, it is evident that the general con- 

 figuration of the choline molecule is essential for lipotropic activity. How- 



722 H. J. Channon and J. A. B. Smith, Biochem. J., 30, 115-120 (1936). 



723 H. J. Channon, A. P. Piatt, and J. A. B. Smith, Biochem. J., 31, 1736-1742 (1937). 



724 V. du Vigneaud, J. P. Chandler, S. Simmonds, A. W. Moyer, and M. Cohn, /. Biol. 

 Chem., 164, 603-613 (1946). 



