COPPER-INDUCED AND MALONDIALDEHYDE-INDUCED MODIFICATION OF HIGH-DENSITY-LIPOPROTEIN AND PARALLEL LOSS OF LECITHIN-CHOLESTEROL ACYLTRANSFERASE ACTIVATION

Incubation of high density lipoproteins (HDL) with 0.1-10 mu M copper ions resulted in a decrease in tryptophan residues and a moderate dimi nution of lysine residues. Polymerization of apolipoprotein AI (ape A- I) was only observed for the highest concentration of Cu2+. A dose-dep endent loss in lecithin cholesterol acyl-transferase (LCAT) activity w as noted. Following incubation with 10 mM malondialdehyde, the physico chemical properties of HDL were more pronouncedly affected, in terms o f lipid peroxidation products, relative electrophoretic mobility and p ercentages of intact tryptophan and lysine residues. Polymerization of apo A-I occurred after 40 min incubation, and a time-dependent loss o f LCAT activation was noted. Since the deficiency in LCAT activation w as observed in relatively mild conditions, when no perturbation of the physico-chemical properties of the particle could be shown, the deter mination of LCAT activity appears to be a sensitive test for HDL discr ete modification.