X. EFFECTS OF DEFICIENCY 83 



than in controls. ^^- Fatty livers on low choline diets were prevented by ni- 

 acinamide or by a deficiency of thiamine. These results were believed due 

 to an impairment of the metabolism of the rat rather than to a specific 

 defect involving niacin or thiamine. 



It is not possible to discuss the many investigations that indicate impor- 

 tant relationships of folic acid, folinic acid, and B12, or their derivatives, 

 to choline and to methyl metabolism. That certain of these factors may be 

 involved in transmethylation, in formate-to-methyl synthesis, or in the 

 betaine-glycine-aminoethanol system appears highly probable. In so far as 

 the rat is concerned, observations up to the present time have demonstrated 

 that its ability to synthesize the methyl and the aminoethanol portions of 

 choline depends on one or more of these newer vitamins. Schaefer 

 et alP' i^^-i^^ have demonstrated that the requirement of choline for the 

 prevention of renal lesions and for the maintenance of normal liver lipids 

 in young rats on a diet low in choline and in methionine may be decreased 

 as much as one-half by the addition of B12 and folic acid. These nutrients 

 appeared to increase the utilization of betaine and methionine in the methyl- 

 ation of aminoethanol to choline and of betaine in the methylation of homo- 

 cystine to methionine. In general, B12 was effective alone if present in ade- 

 quate amounts. If present at a subnormal level, its value was improved by 

 folic acid. The latter was believed ineffective in the absence of B12. Hale 

 and Schaefer noted that w^eanling rats of the Sprague-Dawley strain had a 

 lower choline requirement for protection against renal hemorrhage and a 

 higher requirement for prevention of fatty livers than young of the Alabama 

 Experiment Station strain. ^^^ Lipotropic activity was ascribed to B12 in the 

 experiments of Gyorgy^*'^' ^^^ and to B12 and folic acid in the studies of 

 Drill"^' 1^^ and of Fischer. ^^° Growth of rats on diets devoid of labile methyl 

 and containing B12 and folic acid was reported by Bennett, ^^°'' by Stekol,'^"^ 

 and by du Vigneaud.'^"'^ 



82 P. Handler and F. Bernheim, J. Biol. Chern. 148, 649 (1943). 



83 A. E. Schaefer, W. D. Salmon, and D. R. Strength, Proc. Soc. Exptl. Biol. Med. 

 71, 193 (1949). 



8< A. E. Schaefer, W. D. Salmon, D. R. Strength, and D. H. Copeland, J. Nutrition 

 40,95(1950). 



85 A. E. Schaefer and J. L. Knowles, Proc. Soc. Exptl. Biol. Med. 77, 655 (1951). 



86 O. M. Hale and A. E. Schaefer, Proc. Soc. Exptl. Biol. Med. 77, 633 (1951). 



87 P. Gyorgy ahd C. S. Rose, Proc. Soc. Exptl. Biol. Med. 73, 372 (1950). 



88 C. S. Rose, T. E. Machella, and P. Gyorgy, Proc. Soc. Exptl. Biol. Med. 64, 352 

 (1947); 67, 198 (1948). 



89 H. M. McCormick and V. A. Drill, Proc. Soc. Exptl. Biol. Med. 74, 626 (1950). 

 9" M. A. Fischer and G. D. Hall, Federation Proc. 11, 211 (1952). 



^'"'M. A. Bennett, J. Biol. Chem. 163, 247 (1946); 187, 751 (1950). 

 "Ob J. A. Stekol and K. W. Weiss, J. Biol. ('hem. 186, 343 (1950). 

 ^''^ V. du Vigneaud, C. Ressler, J. R. Rachele, J. A. Reyniers, and T. D. Luckey, 

 J. Nutrition 45, 361 (1951). 



