664 VI. OCCURRENCE OF LIPIDS IN THE ANIMAL 



that the benefit of lipotropic agents is to be traced to their effect in stimu- 

 lating phospholipid synthesis. Increased amounts of phospholipids were 

 found, when methionine or choline was given to patients with cirrhotic 

 livers, as compared with the amount noted in untreated individuals. The 

 beneficial effects of these lipotropic agents on phospholipid synthesis could 

 be observed only if the animals had previously been receiving a choline- 

 deficient diet. Cayer and Cornatzer 736 reported that the beneficial effect 

 of methionine or of choline on the phospholipid turnover of two cirrhotic 

 patients was noted only at the initiation of the treatment. It is also evi- 

 dent that, in this connection, the lipotropic agent is active in stimulating 

 phospholipid turnover only when a relative deficiency in lipotropic agents 

 exists. Patterson and associates 737 also demonstrated that choline defi- 

 ciency decreases the rate of turnover of phospholipid. 



Another fact supports the lecithin theory in explaining the lipotropic 

 effect of choline, i.e., the antilipotropic action of cholesterol has been shown 

 by Aylward et al. 370 to be associated with a decreased amount of phospho- 

 lipid. It was found that a reduction of the phospholipid content of the 

 liver preceded the fatty infiltration. When choline was administered, the 

 phospholipid content was maintained, and the fatty liver did not develop. 

 Finally, the finding of Welch and Welch 715 that phosphoryl choline, which 

 would be expected to act as an intermediate in phospholipid synthesis, is 

 unaffected by liver phosphatase and hence is protected from oxidation, 

 would offer support to the assumption of the direct utilization of choline in 

 the synthesis of lecithin. 



Only one report is in disagreement with the hypothesis that choline owes 

 its lipotropic activity to a stimulation of the rate of phospholipid turnover. 

 That is the report of Perlman et a/., 738 which indicates that two decidedly 

 antilipotropic substances, i.e., cystine and cysteine, also stimulate phos- 

 pholipid turnover in the liver. However, as a possible explanation for these 

 discrepancies, it has been suggested 547 that the phospholipid turnover was 

 studied several hours after the administration of cystine, and the lipotropic 

 activity was investigated after the daily feeding of the cystine for several 

 weeks. 



The weight of evidence thus preponderantly supports the hypothesis that 

 the action of choline precursors in preventing fatty livers is related to their 

 function as an essential component in the in vivo synthesis of phospholipid. 



736 D. Cayer and W. E. Cornatzer, Science, 109, 613-615 (1949). 



737 J. M. Patterson, N. B. Keevil, and E. W. McHenry, J. Biol. Chem., 153, 489-493 

 (1944). 



73 « I. Perlman, N. Stillman, and I. L. Chaikoff, J. Biol. Chem., 135, 359-364 (1940). 



