72 CHOLINE 



supplement lasting 6 or more hours. Betaine was less effective than choline. 

 The latter substance was particularly active in rats fed cholesterol.'^^ There 

 was little indication in these experiments of variations in the total phospho- 

 lipid content of the liver. A slight increase in this fraction of liver lipids 

 following the administration of choline or methionine was noted by Horn- 

 ing and Eckstein, but this was not correlated necessarily with lipotropic 

 activity.''^ 



Artom and Swanson observed that slices from livers of rats previously 

 fed a low choline, low protein diet incorporated P^^ into phospholipids at a 

 slower rate than slices from rats fed high protein diet or a stock diet. Prior 

 administration of choline in vivo reversed the fatty infiltration but did not 

 restore the ability of the isolated liver to synthesize phospholipids. In fact, 

 the addition of choline in vitro inhibited phospholipid formation.''"' Boxer 

 and Stetten fed N^^-labeled choline to rats and found the rate of replace- 

 ment of phospholipid choline in the liver to be 3.9 mg. per rat per day. 

 With cessation of the labeled choline supplement, new, non-isotopic choline 

 replaced the isotopic fraction at a rate of 1.3 mg. per day while fatty livers 

 developed. They concluded that the fatty livers were due to a decrease in 

 the rate of incorporation of choline into tissue phospholipids.^* The admin- 

 istration of choline and of aminoethanol increased the rates of formation 

 of lecithin and of cephalin, respectively, in fasted and fed rats previously 

 given radioactive phosphate .^^ Partial hepatectomy impaired the formation 

 of intestinal and hepatic phospholipids,*"- *^ but choline was ineffective in 

 preventing the resulting fatty liver .*^ 



Deposition of excess lipids in the liver may result from many and diverse 

 causes, and, in certain instances, choline is without effect as a lipotropic 

 agent. Best has summarized the pertinent facts in this field.*^ Of particular 

 significance is the distribution of accumulating fat, in the center of liver 

 lobules if due to hypolipotropism and in the periphery if due to the activity 

 of the anterior pituitary or to extracts of this gland. The administration of 

 anterior pituitary extract in fasting guinea pigs, rats, and mice mobilized 

 body fat in the liver.*^' *^ Inasmuch as this result did not occur if the ad- 

 renals were removed, MacKay concluded that the effect was mediated 



'6 I. Perlman and I. L. Chaikoff, J. Biol. Chem. 128, 735 (1939). 

 7«M. G. Horning and H. C. Eckstein, /. Biol. Chem. 166, 711 (1946). 

 " C. Artom and M. A. Swanson, J. Biol. Chem. 193, 473 (1951). 

 '8 G. E. Boxer and D. Stetten, Jr., J. Biol. Chem.. 153, 617 (1944). 

 ->^ A. P. Piatt and R. R. Porter, Nature 160, 905 (1947). 

 8« E. Chargaff, J. Biol. Chem. 128, 587 (1939). 



81 E. Chargaff, K. B. Olson, and P. F. Partington, J. Biol. Chem.. 134, 505 (1940). 



82 E. M. MacKay and H. 0. Carne, Proc. Soc. Exptl. Biol. Med. 38, 131 (1938). 



83 C. H. Best, Federation Proc. 9, 506 (1950). 



8^ C. H. Best and J. Campbell, J. Physiol. (London) 86, 190 (1936); 92, 91 (1938). 

 86 J. Campbell and C. C. Lucas, Biochem. J. 48, 241 (1951). 



