240 V. OXIDATION AND METABOLISM OP PHOSPHOLIPIDS 



both the British and the American groups of workers are to be credited 

 with the discovery of the existence of choline oxidase. 



The enzyme is present in high concentration in the hver. Kensler and 

 Langemann,^^ using the centrifugation technic, found that the chohne oxi- 

 dase activity was concentrated in the mitochondrial fraction (78%), while 

 only insignificant amounts were present in the nuclear (9%) and superna- 

 tant (13%) fractions. The distribution was found to be similar to that of 

 succinoxidase, although probably not identical with it. The absence of 

 CO in the isolated nuclei of liver cells confirms an earlier report of Lan.'^ 



(6) Chemical Nature of Choline Oxidase. Apparently choline oxidase is 

 a protein, since it has been shown to be inactivated by trypsin and papain." 

 Williams^^ presented evidence to indicate that mitochondrial CO requires 

 a heat-stable co-factor, since aging has been shoAvn to decrease the CO ac- 

 tivity of mitochondrial suspensions. 



The inhibitory effect of folic acid upon the activity of CO appears to be 

 indirect;'^ evidently its action consists in regulating the synthesis of the 

 enzyme protein, rather than in exerting a direct inhibitory effect. Wil- 

 liams^" found that folic acid and aminopterin had no effect upon the CO 

 activity of rat liver when added in vitro, although when they were fed they 

 inhibited the action of this enzyme. On the other hand. Dinning and col- 

 laborators^^ reported that the bone-marrow of chickens, which normally ex- 

 hibits CO activity, did not have this activity if the birds had previously 

 been treated with aminopterin, which is generally accepted as a folic acid 

 inhibitor. This is interpreted as evidence of the displacement of folic acid 

 (pteroylglutamic acid) from its position in the enzyme system by aminop- 

 terin. Dinning, Keith, and Day^^ likewise recorded that the CO content 

 of the livers and kidneys of folic acid-deficient monkeys is reduced; pre- 

 sumably this results because folic acid is the prosthetic group of CO. 

 Williams^^ states that only folic acid and ascorbic acid stimulate choline 

 oxidation in normal rat livers. The results indicate that folic acid (PGA), 

 Leuconostoc citrovorum factor (LCF), vitamin B12, and ascorljic acid are all 

 important in maintaining choline oxidase. 



25 C. J. Kensler and H. Langemann, /. Biol. Chem., 192, 551-554 (1951). 



2« T. H. Lan, /. Biol. Chem., 151, 171-175 (1943). 



" F. Bernheim, /. Biol. Chem., 133, 141-144 (1940). 



28 J. N. Williams, Jr., /. Biol. Chem., 197, 709-715 (1952). 



" J. N. Williams, Jr., M. L. Sunde, W. W. Cravens, and C. A. Elvehjem, J. Biol. 

 Chem,., 185, 895-901 (1950). 



50 J. N. Williams, Jr., J. Biol. Chem., 187, 47-54 (1950). 



" J. S. Dinning, C. K. Keith, P. L. Davis, and P. L. Dav, Arch. Biochem., 27, 89-93 

 (1950). 



'2 J. S. Dinning, C. K. Keith, and P. L. Day, Arch. Biochem.. 24, 4G3-464 (1949). 



33 J. N. Williams, Jr., J. Biol. Chem., 192, 81-85 (1951). 



