HYDROLYSIS I'KODLCTS OP PHOSPHOLIPIDS 243 



tivation parallels the amount of oxidized fatty acids formed, as measured 

 by the thiobarbituric acid reagent. Quercitin, which protects the fat from 

 oxidation, prevents this inactivation. 



It has been reported that ethionine, C2H5S • CHo • CHo • CH(NH2) • COOH, 

 causes a decrease in activity of two systems concerned with choline oxida- 

 tion, namely CO and sarcosine oxidase/®-''^ On the other hand, succin oxi- 

 dase is not affected by this analogue of methionme. Other methionine 

 analogues, methoxmine, and methionine sulfoximine, do not influence CO 

 activity when added in vitro to preparations of hver.'*^ Swendseid et aU'' 

 suggest that the actual inhibitor is not ethionine but an enzymatically 

 produced derivative. Ethionine likewise exerts an inhibitory effect upon 

 CO in vivo^^ 



Barron and associates'^^ noted that the nitrogen mustards inhibit all en- 

 zymes concerned with choline metabolism, including CO. The action of 

 the latter enzyme system was found to be inhibited by as small an amount 

 as 1 X 10~^ M solutions of HNo, methyl-bis (/3-chloroethyl) amine HCl, or 

 HN3, methyl-tris (/3-chloroethyl) amine HCl. Boyland'*^ suggests that the 



inhibition is probably due to the action of the ethylene imonium form of the 



+ 

 bases, R — N=(CH2'CH2), in which form the nitrogen mustards have a 

 con\ailsant and rapidly lethal action.^" This, in turn, might be ascribed to 

 the inhibition of the enzymes concerned with choline metabolism.** Ac- 

 cording to Howe and associates,^ ^ choline affords no protection against ni- 

 trogen mustard intoxication. The aliphatic chloroethyl amines react with 

 most cell constituents,^- including enzymes. CO is inhibited by these sub- 

 stances.^' This effect may be counteracted by the addition of choline." 

 According to AVilliams,-^ CO is partially inactivated by freezing and 

 thawing; a potent, heat-labile inhibitor of CO is present in the supernatant 

 fraction.^* Moreover, boiled extracts of CO were found to increase the ac- 



« M. E. Swendseid, A. L. Swanson, and F. H. Bethell, Federation Proc, 10, 257 ( 1951). 



" M. E. Swendseid, A. L. Swanson, and F. H. Bethell, J. Biol. Chem., 201, 803-809 

 (1953). 



« E. S. G. Barron, G. R. Bartlett, and Z. B. Miller, /. Exptl. Med., 87, 489-501 

 (1948). 



^3 E. Boyland, Ann. Rev. Biochem., 18, 217-242 (1949). 



50 E. Boyland, Brit. J. Pharmacol. Chemotherap., 1, 247-254 (1946). 



" G. W.Howe, H. X. Marvin, and C. L. Spurr, Texas Repts. Biol, and Med., 10, 39- 

 44(1952). 



'^ J. S. Fruton, W. H. Stein, M. A. Stahmann, and C. Golumbic, J. Org. Chem., 11, 

 471-580(1946). 



" E. S. G. Barron, G. R. Bartlett, Z. B. Miller, J. Meyer, and J. E. Seegmiller, /. 

 Exptl. Med., 87, 503-519 (1948). 



" J. N. Williams, Jr., J. Biol. Chem., 194, 139-142 (1952); 198, 579-585 (1952). 



