LIPID STORAGE UNDER ABNORMAL CONDITIONS 659 



methyl group from a methyl "donor" to a methyl "acceptor" is now com- 

 monly known as transmethylation. 



i'. The Comparative Lipotropic Action of Choline Analogues: Follow- 

 ing the discovery of the lipotropic action of choline, betaine was the next 

 compound which was proved to have a lipotropic action. Best and Hunts- 

 man 576 reported that betaine has a lipotropic activity; this behavior has 

 been confirmed by a number of investigators, 713-715 whose results suggested 

 that the lipotropic activity of betaine was from one-third to one-half that of 

 choline. This would indicate that only one methyl group in betaine is 

 available for transmethylation. Piatt 714 is of the opinion that the lower 

 potency of betaine, as compared with choline, may be explained by the fact 

 that it must first be converted to choline in the liver. However, du 

 Vigneaud and associates, 716 using betaine labeled with N 15 and D, found that 

 it was an extremely effective methyl donor. Methyl groups appeared in 

 tissue choline as rapidly after the administration of betaine as following that 

 of choline. Since a disparity in the amount of N 15 and D obtained, it was 

 concluded that the betaine molecule is not converted as a whole to choline. 

 In addition to ordinary betaine (glycine-betaine), only alanine-betaine 717 

 and cystine-betaine 619 have lipotropic activity. Negative results were 

 obtained on a large number of other betaines, including ergothionine 

 (thiolhistidine-betaine), 656,717 - 718 trigonelline (nicotinic acid-betaine), 717 and 

 the betaines of glutamic acid, 717 serine, threonine, and allothreonine. 719 

 The fact that colamine (ethanolamine) is not lipotropic would seem to in- 

 dicate that cephalins are of little importance in the metabolism of fatty 

 acids. 714 Creatine, likewise, has been shown to be devoid of activity in 

 removing fats from the liver. 



Mawson and Welch, 720 as well as Barrenscheen and Pantlitschko, 721 

 demonstrated that the hydroxyl group of choline is necessary for its 

 lipotropic action. Esterification abolishes the lipotropic activity. 721 Tri- 

 methyl ammonium chloride actually caused an increase in liver fat, while 

 trimethylethyl-, tetramethyl-, and trimethylphenylammonium chloride 

 were too toxic to be tested for lipotropic activity. The length of the 



713 W. H. Griffith and D. J. Mulford, J. Am. Chem. Soc, 68, 929-932 (1941). 



714 A. P. Piatt, Biochem. J., 33, 505-511 (1939). 



715 A. D. Welch and M. S. Welch, Proc. Soc. Exptl. Biol. Med., 39, 7-9 (1938). 



716 V. du Vigneaud, S. Simmonds, J. P. Chandler, and M. Cohn, J. Biol. Chem., 165, 

 639-648 (1946). 



717 A. W. Moyer and V. du Vigneaud, /. Biol. Chem., 143, 373-382 (1942). 



718 C. H. Best and J. H. Ridout, Ann. Rev. Biochem., 8, 349-370 (1939). 



719 H. E. Carter and D. B. Melville, /. Biol. Chem., 133, 109-116 (1940). 



720 E. H. Mawson and A. D. Welch, Biochem. J., SO, 417-418 (1936). 



721 H. K. Barrenscheen and M. Pantlitschko, Z. physiol. Chem., 284, 250-256 (1949). 



