242 V. OXIDATION AND METABOLISM OF PHOSPHOLIPIDS 



foxide must precede transmethylation. Only liver and adrenal are able to 

 synthesize choline from methionine and ethanolamine or serine. It has 

 also been reported that, before choline can be formed from methionine and 

 ethanolamine (or serine) in the liver, the preparation must be activated by 

 ascorbic acid-cobalt in the presence of CO; however, ascorbic acid alone 

 does not bring about this synthesis,^" and in fact has an inhibitory effect. 



(d) Factors Altering the Activity or Concentration of Choline Oxidase. Ac- 

 cording to Kensler and Langemann,'" a marked species variation in CO 

 activity obtains in the tissues. Thus the CO activity and the capacity 

 to utilize choline for the methylation of homocysteine are low or absent in 

 fresh human liver, just as in the liver tissue of guinea pig or rabbit. Hand- 

 ler ^^ likewise observed that no CO is present in guinea pig liver; it is pos- 

 sible that this may be one of the reasons why fatty livers cannot be pro- 

 duced in this species. However, the livers of the species examined (rat, 

 mouse, guinea pig, rabbit, chicken, dog, and man) were all found to be 

 capable of utilizing betaine and its sulfur analogue, dimethylthetin, to 

 methylate homocysteine to form methionine. ^^ 



Bernheim^' was the first to demonstrate that the activity of CO is in- 

 hibited by the presence of fatty acids. This inhibitory effect of fats on CO 

 was found to be quite specific, inasmuch as CO is by far the most sensitive 

 (61%); the inhibition of other oxidases by stearic acids was considerably 

 less: succinoxidase (19%), cytochrome (13%), d-amino acid oxidase 

 (8%), amme oxidase (0%). It is suggested that, since CO is especially ac- 

 tive in effecting the oxidation of choline in normal phospholipid catabolism, 

 sufficient choline might not be available for phospholipid synthesis unless 

 there were some inhibitory action on CO. The results of Humoller and 

 Zimmerman"** likewise support the finding that a high concentration of 

 fatty acids greatly inhibits the action of CO. Thus, in rats fed a diet high 

 in fats and low in choline, the CO activity decreased precipitously during 

 the first week of the diet, concomitantly with the increase in liver fat. 

 Moreover, the CO acti^dty could not be augmented in the fatty livers when 

 choline or betaine was injected two hours before the animals were sacrificed. 



The activity of CO has been sho\ATi to be inhibited by oxidized fatty 

 acids. Thus, Bernheim and co-workers'*^ reported that the extent of inac- 



« H. K. Barrenscheen and I. Skudrzyk, Z. physiol. Chem., £84, 228-236 (1949). 

 " C. J. Kensler and H. Langemann, Pwc. Soc. Exptl. Biol. Med., 85, 364-367 (1954). 

 « P. Handler, Proc. Soc. Exptl. Biol. Med., 70, 70-73 (1949). 

 " F. Bernheim, /. Biol. Chem., 133, 291-292 (1940). 



" F. L. Humoller and H. J. Zimmerman, Am. J. Physiol., 174, 199-202 (1953). 

 « F. Bernheim, K. M. Wilbur, and C. B. Kenaston, Arch. Biochem., 38, 177-184 

 (1952). 



