646 VI. OCCURRENCE OF LIPIDS IN THE ANIMAL 



sumably of any other protein — was due to "a resultant effect of the simul- 

 taneous opposing influences of the cystine and the methionine of the diet." 

 This work was almost immediately confirmed by Channon, Manifold, and 

 Piatt. 627 - 628 Methionine was found to be active on both the glyceride and 

 the cholesterol fractions of liver; this amino acid was first calculated to 

 have a choline equivalent of one-twelfth, 627 but this figure was later revised 

 to one-fifth. 628 The D- and L-isomers were found to have equal potency as 

 lipotropic agents. 629 Singal and Eckstein 609 found that methionine exerts a 

 lipotropic action on mice similar to that on the rat. Harper et al. 614 re- 

 ported that DL-threonine is capable of reducing fat in the liver of rats when 

 incorporated in the diet to the extent of 0.18%. 



(d') The Quantitative Relationship of Lipotropic and Antilipotropic 

 Action : Treadwell 630 suggested that the requirement for methionine in the 

 rat is based upon two considerations, namely, that for the growth demands, 

 and that for lipotropism. The latter requirement is obviously conditioned 

 by the amount of other lipotropic factors in the diet. The total methionine 

 necessary for optimal growth in the rat was set at 600 mg. per day, and that 

 for lipotropic action at a level of 600 mg. per 100 g. of food. When the diet 

 contained 100 milligram per cent of cystine, 631 together with 500 milligram 

 per cent of methionine, and 18.6% of protein, fatty livers and hemorrhagic 

 kidneys developed in young white rats. Under these conditions, the meth- 

 ionine requirement was reported to be 1300 to 1500 mg. per 100 g. of diet. 

 When the diet contained 200 milligram per cent of cystine, an antilipo- 

 tropic effect was noted, and a significant increase in growth rate. At the 

 highest level at which cystine was tested (400 milligram per cent), death 

 occurred within fourteen days in 85% of the rats. 



On the other hand, 100 milligram per cent of choline in the diet produced 

 the maximum reduction of liver fat. 630 Treadwell 631 reported the greatest 

 stimulation of growth in young rats at the 200 milligram per cent level. 

 Liver fat was also found to be normal when this diet was fed. It is believed 

 that the growth-stimulating effect of choline is due to its methionine-spar- 

 ing action. 



Best and collaborators 632 pointed out the necessity for preparing dose- 

 response curves for the accurate estimation of lipotropic requirements un- 



627 H. J. Channon, M. C. Manifold, and A. P. Piatt, Biochem, J., 32, 969-975 (1938). 



628 H. J. Channon, M. C. Manifold, and A. P. Piatt, Biochem. J., 34, 866-878 (1940). 



629 C. H. Best and J. H. Ridout, J. Physiol, 97, 489-494 (1940). 



630 C. R. Treadwell, /. Biol. Chem., 160, 601-607 (1945). 



631 C. R. Treadwell, /. Biol. Chem., 176, 1141-1147 (1948). 



632 C. H. Best, C. C. Lucas, J. H. Ridout, and J. M. Patterson, /. Biol. Chem., 186, 

 317-329 (1950). 



