662 VI. OCCURRENCE OF LIPIDS IN THE ANIMAL 



ever, the segments may be substituted (as ethyl for methyl), and nitrogen 

 may be replaced by other elements of suitable valency, for example phos- 

 phorus or arsenic. The hydroxyl group must also be present if the com- 

 pound is to be active. 



j'. The Physiologic Role of Choline and Its Method of Action: 

 The most important function of choline is its lipotropic action. Although 

 this influence on fatty livers is obviously related to its occurrence in 

 lecithin, other more complicated explanations have been offered. These 

 include the hypothesis that choline acts by virtue of an undefined role in 

 liver function, or that it controls carbohydrate metabolism. These theories 

 have not been substantiated, so it would appear that choline is needed for 

 the synthesis of lecithin. Choline is also of importance in kidney growth 

 and development, as a precursor of acetylcholine, as a required dietary 

 constituent during lactation, and as one of the required dietary agents for 

 preventing perosis. 



(a') The Mode of Action of Choline as a Lipotropic Agent: The preven- 

 tion of fatty livers is undoubtedly connected with the maintenance of an 

 adequate transport mechanism between the liver and the fat depots, and 

 vice versa. Since the original work of Leathes and Raper, 13 it has generally 

 been accepted that phospholipids function in fat transport. This hy- 

 pothesis has been strengthened by the experimental results summarized 

 by Bloor, 117 and by Sinclair, 369 in their articles in Physiological Reviews. 



The results of Fishman and Artom 725 furnish circumstantial evidence of 

 the importance of choline in lecithin synthesis. Thus, it was found that 

 the level of lecithin in the liver and tissues of young rats was lower than 

 normal when the animals had received a choline-low diet from weaning. 

 Proof that choline plays a direct part in phospholipid synthesis is afforded 

 by the data of Welch, 726 of Welch and Landau, 727 and by those of Stet- 

 ten, 660,728 which demonstrated the incorporation of this substance into phos- 

 pholipid. Thus, following the administration of arsenocholine, which 

 proved to be lipotropic, the arsenic analogue of lecithin was found in the 

 tissues. 726,727 The finding that the methyl groups in arsenocholine are not 

 labile 717 would seem to constitute further evidence that the lipotropic action 

 depends upon the availability of the entire choline molecule (or arsenocho- 

 line molecule) for incorporation into a newly-formed phospholipid molecule. 

 Furthermore, triethylcholine was also found by Welch, 726 by McArthur el 



725 W. H. Fishman and C. Artom, J. Biol. Chem., 154, 109-115 (1944). 

 72 ° A. D. Welch, Proc. Soc. Exptl. Biol. Med., 35, 107-108 (1936). 



727 A. D. Welch and R. L. Landau, J. Biol. Chem., 144, 581-588 (1942). 



728 De W. Stetten, Jr., J. Biol. Chem., 138, 437-438 (1941). 



