X. EFFECTS OF DEFICIENCY 77 



IV). The similar behavior of most proteins depends on their content of 

 this amino acid inasmuch as it is the only one of these units commonly 

 present in proteins for which significant lipotropic activity has been demon- 

 strated. ^^^-^^^ 



The effect of cystine and its apparent antagonism to methionine have 

 intrigued many investigators. Beeston and Channon noted that the cystine 

 effect was not proportional to the level of the cystine supplement, ^-^ and 

 this may explain the minimal influence of additions of the amino acid to 

 low choline, low protein diets in which the protein was gliadin^^^ or albu- 

 min, i**" both relatively richer in cystine than casein. Attempts to compare 

 the lipotropic activity of free methionine with equivalent amounts in vari- 

 ous proteins have not yielded uniformly consistent results. ^^"' ^^^- ^^'^ • 140-143 

 This is not surprising in view of differences in strains and in the age of 

 experimental rats, of changes in the nutritional state of the animals in 

 those instances in which a deficiency of protein was superimposed on a 

 deficiency of methyl, of variations in the supply of cystine, and of the 

 unrecognized presence in some diets of nutrients, such as B12, which are 

 now believed to influence favorably the utilization of methionine. 



Somewhat more consistent results have been obtained in studies of the 

 cystine effect in weanling rats. Griffith and Wade noted clear evidence of 

 the aggravating effect of added cystine on both renal lesions and deposition 

 of liver fat on diets ordinarily considered adequate in total protein.'^^ Cox 

 et al. had observed this result before choline was recognized as a dietary 

 factor."^ In line with data obtained on older rats,^-® the maximum cystine 

 effect in weanling rats fed a diet containing 0.05 % choline chloride and 18 % 

 casein resulted if 0.1 to 0.2% additional cystine was added. Cystine sup- 

 plements up to 2 % had no additional effect.-^ These data emphasized the 

 physiological role of a small supplement of cystine and removed any basis 

 for an explanation of the cystine effect because of toxicity. Mulford and 

 Griffith demonstrated that the addition of extra cystine to the 18 % casein 

 diet supplemented with sufficient choline to prevent fatty livers resulted in 

 improved growth of the rats as measured by increased ""body weight and 

 length and efficiency of utilization of food. Accordingly, it was concluded 



136 H. J. Channon, J. V. Loach, P. A. Loizides, M. C. Manifold, and G. Soliman, Bio- 



chem. J. 32, 976 (1938). 

 1" H. F. Tucker and H. C. Eckstein, /. Biol. Chern. 126, 117 (1938). 

 "8 W. H. Griffith, J. Nutrition 21, 291 (1941). 



"9 M. G. Horning and H. C. Eckstein, J. Biol. Chem. 155, 49 (1944). 

 1" H. J. Channon, M. C. Manifold, and A. P. Piatt, Biochem. J. 34, 866 (1940). 

 1" C. R. Treadwell, M. Groothuis, and H. C. Eckstein, J. Biol. Chem. 142, 653 (1942). 

 i« J. M. R. Beveridge, C. C. Lucas, and M. K. O'Grady, J. Biol. Chem. 154, 9 (1944). 

 1" H. F. Tucker, C. R. Treadwell, and H. C. Eckstein, J. Biol. Chem. 135, 85 1940). 

 1" G. J. Cox, C. V. Smythe, and C. F. Fishback, /. Biol. Chem. 82, 95 (1929). 



