650 VI. OCCURRENCE OF LIPIDS IN THE ANIMAL 



methionine, proved that, when ethionine was present, a decrease of about 

 20% obtained in the extent of transmethylation from methionine to choline. 

 However, the amount of creatine synthesized from dietary methionine was 

 not decreased by the presence of ethionine in the diet. Hardwick and 

 Winzler 649 also reported a lipotropic action on the part of ethionine when it 

 was fed along with carbohydrates. Levine and Fopeano 650 likewise re- 

 ported a reduction of liver fat in male rats receiving ethionine as compared 

 with control animals ; in this case, the decrease is attributed to a decreased 

 food consumption. On the other hand, the feeding of ethionine to female 

 rats caused an increase in liver lipid, irrespective of whether or not choline 

 was also given. It is postulated that the administration of methionine 

 results in the formation and accumulation of abnormal protein in the liver. 



g'. The Biological Synthesis of Choline: The demonstration of the mecha- 

 nism of synthesis of choline in the animal body has been one of the bril- 

 liant accomplishments of the last decade. At the same time, it has solved 

 many mysteries in the understanding of the effect of amino acids on liver 

 fats. The biosynthesis of choline was reviewed by du Vigneaud. 651,652 



The clue to the mechanism responsible for the synthesis of choline de- 

 veloped as the result of diametrically opposite conclusions obtained by 

 two groups of workers who were investigating whether or not homocystine, 

 in place of methionine, could support the growth of rats. Womack and 

 colleagues 653 had previously demonstrated that the amino acid, methionine, 

 was essential for growth. Although du Vigneaud et al. ebi showed that ho- 

 mocystine could not support the growth of rats on a diet containing all the 

 essential amino acids except methionine, together with a vitamin B sup- 

 plement consisting of thiamine chloride, riboflavin, nicotinic acid, and 

 ryzamin B, they did find that growth occurred when a tikitiki extract (rice 

 polishings) and milk concentrate were added. Similar results were ob- 

 tained by Rose and Rice. 655 It was suggested that the factor permitting 

 growth when these supplements were added to the homocystine diet might 

 be choline. 656 It was then shown that, when choline was added to the de- 

 ficient diet, growth resulted. Presumably growth occurs because choline 



649 V. L. Hardwick and R. J. Winzler, Proc. Soc. Exptl. Biol. Med., 69, 217-219 (1948). 

 660 M. Levine and J. F. Fopeano, Federation Proc, 12, 238 (1953). 



651 V. du Vigneaud, Biol. Symposia, 5, 234-247 (1941). 



652 V. du Vigneaud, Harvey Lectures, 38, 39-62 (1942-1943). 



6" M. Womack, K. S. Kemmerer, and W. C. Rose, /. Biol. Chem., 121, 403-410 (1937). 



654 V. du Vigneaud, H. M. Dyer, and M. W. Kies, /. Biol. Chem., 130, 325-340 (1939). 



655 W. C. Rose and E. E. Rice, J". Biol. Chem., 130, 305-323 (1939). 



656 V. du Vigneaud, J. P. Chandler, A. W. Moyer, and D. M. Keppel, J. Biol. Chem., 

 131, 57-76 (1939). 



