INHIBITORY EFFECTS OF LIPID OXIDATION ON THE ACTIVITY OF PLASMA LECITHIN-CHOLESTEROL ACYLTRANSFERASE

We investigated the effects of free radical generation on the esterifi cation of cholesterol by lecithin-cholesterol acyltransferase (LCAT), A water-soluble free radical initiator, 2,2'-azobis-amidinopropane dih ydrochloride (AAPH), inhibited the activity of plasma LCAT as a functi on of the incubation time after its addition. When a small amount of o xidized HDL was added to plasma, LCAT activity was dose-dependently in hibited. To identify the effects of HDL oxidation on LCAT activity, a purified enzyme and cofactor in a vesicle solution tan artificial subs trate) were used, i) LCAT activity was inhibited by the oxidation of s ubstrate vesicles, this inhibition being related to the degree of oxid ation. ii) This inhibition was observed even if apolipoprotein A-I was not oxidized. iii) Oxidized phosphatidylcholine, but not oxidized cho lesterol, in the vesicles affected LCAT activity, iv) The addition of 0-40% of oxidized vesicles to normal substrate vesicles resulted in th e activity of LCAT being inhibited in a dose-dependent manner. These r esults suggest that the esterification of cholesterol by LCAT may be a ffected by the oxidation of substrate phosphatidylcholine via free rad ical generation in the plasma.