Some Heavy Metals Affecting the Lecithin-Cholesterol Acyltransferase Reaction in Human Plasma

Abstract

The effects of cadmium (Cd2+) zinc (Zn2+), and calcium (Ca2+) ions on the esterification of cholesterol in sonicated dispersions of lecithin-cholesterol mixtures by lecithin-cholesterol acyltransferase (LCAT) in human plasma were studied in vitro. The acyltransferase activity was slightly stimulated at concentrations of Ca2+ ions ranging from 1×10−5M to 1×10−3M but depressed at concentrations above 1×10−4M Cd2+ ions and above 5×10−4 M Zn2+ ions. The concentration of Zn2+ ions required for 50% inhibition of the acyltransferase activity was approximately twice that of Cd2+ ions. The acyltransferase inhibition caused by the addition of 1×l0−3 M Cd2+ or Zn2+ ions was completely overcome by the addition of 0.1% of ethylenediaminetetraacetic acid (EDTA) but not by the addition of 1×10−3M citrate, cysteine, mercaptoethanol or 22+ ions. The decreased acyltransferase activity in the presence of 1×10−2 M Cd2+ ions increased linearly on the addition of increasing amounts of bovine serum albumin. The decreased acyltransferase activity in the presence of 1×l0−3 M Zn2+ (65.4 μg as Zn per ml of incubation medium) or Cd2+ (112.4 mu;g as Cd per ml of incubation medium) ions was restored to the control level or approximately 70% of the control level, respectively, by the addition of 40 mg of bovine serum albumin per ml of the incubation medium. Thus the molar ratio of Zn2+ binding to bovine serum albumin may be greater than that of Cd2+ binding. In the presence of Cd2+ or Zn2+ ions, the acyltransferase activity toward a dispersion with a lecithin/cholesterol molar ratio of 5.9 was decreased more than that toward a dispersion with a ratio of 1.2. This result suggests that increasing amounts of lecithin in the dispersion added as a substrate may enhance the interfering effect of Cd2+ and Zn2+ ions on the acyltransferase.