X. EFFECTS OF DEFICIENCY 79 



Salmon concluded that weanling rats on diets containing 18% or less 

 casein were subject to methyl deficiency unless supplemental choline or 

 methionine was supplied. ^^^ This deficiency was intensified by cystine and 

 by fat. Such animals also required supplementary nicotinic acid or addi- 

 tional tryptophan unless the diet was high in fat. It was not possible to 

 demonstrate a deficiency of cystine unless the methyl and nicotinic acid 

 deficiencies were remedied. In contrast is the surprising observation of 

 Tyner ei al. that the cystine effect was abolished if generously adequate 

 levels of niacin or of tryptophan were provided."* 



Treadwell and coworkers have also studied the cystine effect in both 

 young and adult rats.^^"*- i^g-isi 'pj^g intensification of renal lesions in wean- 

 ling rats by supplements of cystine was confirmed, but the explanation 

 based on the increased demand for choline because of the otherwise im- 

 proved food mixture was questioned. i''* Treadwell suggested that the me- 

 tabolism of cystine may require methyl groups or that extra cystine may 

 depress the demethylation of methionine by a mass action effect."^ Neither 

 possibility explains the similarity of lipotropism in diets supplemented with 

 0.1 and 2.0 % cystine.-^ The failure of cystine to induce growth on low casein 

 diets, as noted by TreadwelP^^ and by Salmon,"^ is not surprising. Griffith 

 and Nawrocki found that threonine increased the need of choline in cystine- 

 supplemented 8 % casein diets and concluded that at this casein level 

 cystine (or methionine) and threonine were the first and second limiting 

 amino acids, respectively. ^^^ 



The synthesis of choline in rats fed diets containing methionine as the 

 main methyl donor requires a suitable carbon-nitrogen moiety to serve as 

 the methyl acceptor and whatever cofactors are necessary for the enzy- 

 matic systems involved. There appears to be little difficulty in the provision 

 of the dietary essentials for these mechanisms. Rose et al. found no statis- 

 tically significant effect on the growth of weanling rats as a result of the 

 omission of glycine, serine, cystine, and most of the choline from a standard 

 diet containing a mixture of highly purified amino acids as the source of 

 nitrogen.^** The same omissions caused a slight but significant retardation 

 of growth in similar diets in which the methionine level was decreased from 

 0.8 to 0.5% (as DL-methionine) and the threonine level from 0.7 to 0.4% 

 (as L-threonine) and in which the liver extract, a possible source of B12, 

 was also omitted. 



Ethionine (S-ethyl-DL-homocysteine) is a homolog of methionine and is, 



"8 E. P. Tyner, H. B. Lewis, and H. C. Eckstein, /. Biol. Chem. 187, 651 (1950). 



"9 C. R. Treadwell, J. Biol. Chem. 176, 1149 (1948). 



'60 C. R. Treadwell, H. C. Tidwell, and J. H. Gast, /. Biol. Chem. 156, 237 (1944). 



'" C. R. Treadwell, J. Biol. Chem. 160, 601 (1945). 



1" W. H. Griffith and M. F. Nawrocki, Federation Proa. 7, 288 (1948). 



1" W. C. Rose, W. W. Burr, Jr., and H. J. Sallach, J. Biol. Chem. 194, 321 (1952). 



