38 CHOLINE 



Williams^^" observed that rats fed aminopterin exhibit a concentration 

 of liver ascorbic acid which is less than 50 % normal, suggesting that folic 

 acid is probably involved in ascorbic acid synthesis in the rat. His work 

 indicated that, whereas high levels of ascorbic acid in liver extracts stimu- 

 late the choline oxidase system, low levels of this vitamin added in vitro 

 actually inhibit the oxidation of choline. On the basis of these observations 

 Williams postulated that the low ascorbic acid concentration in the liver 

 of rats fed aminopterin may help to explain some of the previous observa- 

 tions on the low choline oxidase activity of livers of those rats. 



Choline oxidase activity was greatly depressed in the fatty liver of rats 

 on a low methionine diet.^^^ It was suggested that the oxidase inhibition may 

 be due to the increased lipid content of the liver, since fatty acids have been 

 shown to be inhibitory to the system.^^* The importance of the choline oxi- 

 dase system in the development of fatty livers caused by choline deficiency 

 is suggested by the observations that guinea pigs which lack the enzyme 

 system cannot be made to develop fatty livers very readily^^^ and that 

 hamsters which have some enzyme but much less than rats do not accumu- 

 late as much liver fat on a deficient diet as do rats."^ A lack of the enzyme 

 system can be considered an advantage when minimal amounts of choline 

 are present for fat transport and metabolism, and the suggestion has been 

 advanced that it is the diminished choline oxidase activity which permits 

 the existence of a normal hepatic choline concentration (as phospholipid) 

 despite a dietary choline deficiency. ^^^' "* The work of Dubnoff^^" and 

 Muntz^"^ showed that the choline oxidase system also plays an important 

 role in transmethylation reactions. However, a mechanism must exist in 

 the guinea pig for the catabolism of choline. Dubnoff injected C^^-methyl- 

 labeled choline and betaine intraperitoneally into this animal and found 

 that both contributed to labeled expired carbon dioxide as well as to labeled 



tissues but the ratio of utilization of betaine methyl to choline methyl was 

 4.6."5 



Liver choline oxidase was decreased by a riboflavin deficiency in 

 rats.^^®' ^" The B^-deficient rat livers showed a reduced activity of about 

 20 to 30 % of the control levels.^" Atabrine, w^hich has been known to in- 

 hibit flavin enzyme systems, in vitro was found to bring about an inhibition 



"9 J. S. Dinning, C. K. Keith, and P. L. Day, J. Biol. Chem. 189, 515 (1951). 



'» J. N. Williams, Jr., Proc. Soc. Exptl. Biol. Med. 77, 315 (1951). 



" P. Handler and F. Bernheim, J. Biol. Chem. 144, 401 (1942). 



" P. Handler, Proc. Soc. Exptl. Biol. Med. 70, 70 (1949). 



" P. Handler and F. Bernheim, Proc. Soc. Exptl. Biol. Med. 72, 569 (1949). 



7* H. P. Jacobi and C. A. Baumann, /. Biol. Chem. 142, 65 (1942). 



'* J. W. Dubnoff, Arch. Biochem. 22, 474 (1949). 



^6 W. Hess and G. Voillier, Helv. Chim. Acta 31, 381 (1948). 



" B. Kelley, Federation Proc. 11, 238 (1952). 



