78 CHOLINE 



that the phenomenon involving cystine was related to its improvement of 

 the nutritive value of the diet, i.e., the removal of the existing sulfur defi- 

 ciency. The resulting increased metabolic level raised the choline require- 

 ment and exaggerated the deficiency signs in the absence of a supply of the 

 required extra choline. This explanation made unnecessary any hypothesis 

 based on a specific antagonism or competition between the sulfur amino 

 acids, methionine and cystine. 



The fact that weanling rats develop severe evidences of deficiency on low 

 choline diets, even on diets adequate in protein, made it possible to study 

 protein effects without the risk of protein deficiency. Griffith fed mixtures 

 of casein, lactalbumin, fibrin, edestin, and gelatin with and without sup- 

 plements of methionine and cystine and found that dietary choline was not 

 required for the prevention of hemorrhagic degeneration if the food mixture 

 provided 0.8% or more methionine, regardless of whether this level was 

 attained by use of proteins or by methionine supplements.^^* Renal lesions 

 and fatty livers occurred on low choline diets providing 10 to 25 % casein,^^' 

 and 30 % casein was required to prevent the cystine effect in the absence 

 of added choline.^^ The latter observation was the basis for the conclusion 

 that a single molecule of methionine is not simultaneously a source of both 

 labile methyl and cystine sulfur, inasmuch as 22 to 24 % casein supplies 

 the optimum level of sulfur if dietary choline is provided.^^ 



The relation between the general adequacy of the diet for growth, except 

 for its choline content, and the deposition of liver fat was emphasized in 

 the first report on choline deficiency in weanling rats. With diets only 

 moderately deficient in choline, the deposition of liver fat was intensified in 

 those permitting the better rates of growth.^ The concept that nutritionally 

 adequate diets involve increased needs of choline, and the converse, that 

 choline requirements are less if the food mixture or the food intake does not 

 allow growth, were supported by the results of caloric restriction in wean- 

 ling rats fed a choline-deficient diet. The development of renal lesions and of 

 fatty livers was completely prevented by removal of part of the carbo- 

 hydrate and fat of the diet.^^ Similar conclusions regarding the nature of 

 the diet and the requirement of choline have been reached by Beveridge 

 et aU^'- 1^2 Salmon,i4* Handler,i^« and Best.122. i^t 



Handler prevented growth in young rats by feeding them a diet deficient 

 in choline and in the mineral component of the ration. After 4 weeks these 

 animals had not grown and the values for liver lipids were nearly normal 

 whereas rats restricted to the same amount of food containing the mineral 

 component grew slowly and had markedly fatty livers. ^^^ 



'" W. D. Salmon, J. Nutrition 33, 155 (1947). 

 >" P. Handler, J. Biol. Chem. 149, 291 (1943). 



"' C. H. Best, C. C. Lucas, J. H. Ridout, and J. M. Patterson, J. Biol. Chem. 186, 

 317 (1950). 



