244 V. OXIDATION AND METABOLISM OF PHOSPHOLIPIDS 



tivity of partially-inactivated extracts.-^ Riboflavin deficiency was shown 

 to decrease the activity of CO in weanling rat liver, while vitamin Be and 

 thiamine deficiencies were without effect. ^^ The rate of inactivation of 

 CO in washed liver homogenates was increased by cystine and by semi- 

 carbazide.^^ 



Several investigators""^^ reported that the incorporation of carcinogenic 

 azo dyes such as dimethylaminoazobenzene (butter yellow, DMAB) into 

 the diet of animals produces a pronounced drop in CO activity. This 

 may result in a block in the transmethylation cycle, since oxidation of cho- 

 line is a prerequisite for methyl transfer. Kensler et al.^ observed that the 

 CO activities of transplantable mouse liver tumors examined were only 

 15, 33, and 50% of that present in normal liver. It is also of interest that, 

 according to Kensler and associates,^ ^ CO is low in the livers of newborn 

 rats, and increases to only one-third of the adult level by the time of wean- 

 ing. Williams and co-workers^^ reported the presence of CO in the livers 

 of the chick embryo. 



c. The Course of Choline Metabolism. Miiller^^ ^^g of \}^q opinion that 

 choline chloride is broken down to trimethylamine, since increased amounts 

 of this compound were found in the urine after the feeding of choline 

 chloride or lecithin. The methyl groups did not originate from creatine. 

 On the basis of a study of liver slices, Artom and Crowder^^ reported that 

 the major pathway of choline metabolism was involved in the formation 

 of water-soluble combinations which were resistant to mild hydrolysis. 

 These resemble phosphorylcholine rather than lecithin or glycerylphos- 

 phorylcholine, which are easily hydrolyzable. Boyd^* noted that, durhig 

 the development of the chick embryo, the labile methyl groups in the liver 

 decreased about 25%. Since it is known that a CO system exists,-^ di- 

 methylaminoacetic acid is probably formed. However, it does not accumu- 

 late, and therefore it is believed that the demethylation product must be 

 rapidly metabolized.^^ An alternative pathway for the metabolism of cho- 



65 D. A. Richert and W. W. Westerfeld, J. Biol. Chem., 199, 829-833 (1952). 



68 G. S. Eadie and F. Bernheim, /. Biol. Chem., 186, 731-739 (1950). 



" G. Viollier, Helv. Physiol. Pharmacol. Acta, 8, C34-C36, C37-C39 (1950). 

 6^ C. J. Kensler and H. Langemann, Cancer Research, 11, 264 (1951). 



69 G. E. Woodward, Cancer Research, 11, 918-921 (1951). 



^" C. J. Kensler, M. Rudden, and H. Langemann, Cancer Research, 12, 274 (1952). 



61 C. J. Kensler, M. Rudden, E. Shapiro, and H. Langemann, Proc. Soc. Exptl. Biol. 

 Med., 75,39-42(1952). 



62 H. Muller, Z. physiol. Chem., 263, 243-258 (1940). 



6' C. Artom and M. Crowder, Arch. Biochem., 29, 227-228 (1950). 

 6^ G. S. Boyd, Biochem. J., 47, xlvii-xvliii (1950). 

 "6 G. S. Boyd, Biochem. J., 49, vii (1951). 



