A novel lecithin-cholesterol acyltransferase antioxidant activity preventsthe formation of oxidized lipids during lipoprotein oxidation

Recent investigations suggest that high-density lipoprotein (HDL) may play an anti-atherogenic role as an antioxidant and inhibit the oxidative modifi cation of low-density lipoprotein (LDL), The antioxidant activity of HDL ha s been proposed to be associated with several HDL-bound proteins. We have p urified one HDL-associated protein, lecithin:cholesterol acyltransferase (L CAT), to apparent homogeneity and have found that LCAT is not only capable of esterifying cholesterol in the plasma, but can also prevent the accumula tion of oxidized lipids in LDL. Addition of pure human LCAT to LDL or palmi toyl-linoleoyl phosphatidylcholine/sodium cholate (PLPC) micelles inhibits the oxidation-dependent accumulation of both conjugated dienes and lipid hy droperoxides. LCAT also inhibits the increase of net negative charge that o ccurs during oxidation of LDL. LCAT has the ability to prevent spontaneous oxidation and Cu2+ and soybean lipoxygenase-catalyzed oxidation of lipids. The antioxidant activity of LCAT appears to be enzymatic, since the enzyme is active for up to 10 h in the presence of mild free-radical generators. T he catalytic serine, residue 181, may mediate this activity and act as a re usable proton donor. Chemical modification of the active serine residue wit h diisopropylfluorophosphate completely inhibits the ability of LCAT to pre vent lipid oxidation. Thus, in addition to its well-characterized phospholi pase and acyltransferase activities, LCAT can also act as an antioxidant an d prevent the accumulation of oxidized lipid in plasma lipoproteins.