X. EFFECTS OF DEFICIENCY 87 



vented by choline .-'' Extremely fatty livers resulted in choline-deficient 

 rats fed at 20 % protein diet for one week following 7 days of fasting or 21 

 days of protein depletion, although choline was effective in these experi- 

 ments.--^ Prolonged feeding of diets low in protein and in choline resulted 

 in severe nutritional anemia and edema in rats.^-^- ^" Both were prevented 

 by choline, and Engel suggested that choline was a more important factor 

 than dietary protein in the development of these abnormalities. The edema- 

 tous condition was associated with hepatic fatty infiltration and subsequent 

 cirrhosis. Anemia was also observed by Diaz et al. in rats fed a choline-de- 

 ficient ration. 2'-* 



Weanling rats fed diets low in protein or in riboflavin or containing io- 

 dinated casein consistently showed decreased levels of liver and kidney 

 choline oxidase. ^-^ Ebisuzaki and Williams observed a parallelism between 

 the flavin adenine dinucleotide and the choline oxidase levels of riboflavin- 

 deficient rats. The latter workers concluded that the riboflavin-containing 

 enzyme system was a part of the hydrogen transport mechanism involved 

 in the oxidation of choline by choline oxidase .^^^ 



Singal et al. produced fatty livers in young rats fed low protein or low 

 amino acid rations deficient in essential amino acids such as lysine and 

 threonine but containing 0.2 % choline.^^' Normal liver lipid levels resulted 

 from supplementation with the missing amino acid. High levels of choline 

 were lipotropic in the animals on the deficient diets but only partly so in 

 those fed the inadequate amino acid mixture. B12 had no lipotropic action 

 in these experiments. As observed by Eckstein,^^- threonine was without 

 effect in the absence of dietary choline. The rate of turnover of liver phos- 

 pholipids was increased by the administration of threonine to threonine- 

 deficient animals, although no such effect was noted in the turnover rate in 

 the kidneys or in the small intestine. These results are of unusual interest 

 in view of the observation that supplements of threonine in a low protein, 

 choline-deficient diet aggravated symptoms in young rats during the period 

 in which the acute phase of the deficiency occurred. ^^- 



2" C. F. Wang, D. M. Hegsted, A. Lapi, N. Zamcheck, and M. B. Black, J. Lab. 

 Clin. Med. 34, 953 (1949). 



225 0. M. Hale and A. E. Schaefer, /. Nutrition 46, 479 (1952). 



226 R. W. Engel, /. Nutrition 36, 739 (1948). 



227 H. D. Alexander and R. W. Engel, J. Nutrition 47, 361 (1952). 



228 C. J. Diaz, H. Castro-Mendoza, G. Paniagua, and F. Vivanco, Bull. Inst. Med. 

 Research, Univ. Madrid 1, 101 (1948). 



229 D. A. Richert and W. W. Westerfeld, J. Biol. Chem. 199, 2 (1952). 



230 K. Ebisuzaki and J. N. Williams, Jr., J. Biol. Chem. 200, 297 (1953). 



231 S. A. Singal, S. J. Kazan, V. P. Sydenstricker, and J. M. Littlejohn, J. Biol. 

 Chem. 200, 867 (1952). 



232 H. C. Eckstein, /. Biol. Chem. 195, 167 (1952). 



