Disparate effects of oxidation on plasma acyltransferase activities: inhibition of cholesterol esterification but stimulation of transesterification of oxidized phospholipids.
Oxidation of lipoproteins results in the formation of several polar phospholipids with pro-inflammatory and pro-atherogenic properties. To examine the possible role of lecithin/cholesterol acyltransferase (LCAT) in the metabolism of these oxidized phospholipids, we oxidized whole plasma with either Cu(2+) or a free-radical generator, and determined the various activities of LCAT. Oxidation caused a reduction in plasma phosphatidylcholine (PC), an increase in a short-chain polar PC (SCP-PC), and an inhibition of the transfer of long-chain acyl groups to cholesterol (LCAT activity) or to lyso PC (lysolecithin acyltransferase (LAT) I activity). However, the transfer of short-chain acyl groups from SCP-PC to lyso PCLAT II activity) was stimulated several fold, in direct correlation with the degree of oxidation. LAT II activity was not stimulated by oxidation in LCAT-deficient plasma, showing that it is carried out by LCAT. Oxidized normal plasma exhibited low LCAT activity even in the presence of exogenous proteoliposome substrate, indicating that the depletion of substrate PC was not responsible for the loss of activity. Oxidation of isolated LDL or HDL abolished their ability to support LCAT and LAT I activities of exogenous enzyme, but promoted the LAT II activity. Purified LCAT lost its LCAT and LAT I functions, but not its LAT II function, when oxidized in vitro. These results show that while oxidation of plasma causes a loss of LCAT's ability to transfer long-chain acyl groups, its ability to transfer short-chain acyl groups, from SCP-PC is retained, and even stimulated, suggesting that LCAT may have a physiological role in the metabolism of oxidized PC in plasma.
Subbaiah
P V
PV
Department of Medicine, Rush Medical College, Chicago, IL 60612, USA.
Liu
M
M
D000328:Adult; D002788:Cholesterol Esters / Q000378:metabolism*; D005260:Female; D006801:Humans; D007863:Lecithin Cholesterol Acyltransferase Deficiency / Q000097:blood; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*
D002788:Cholesterol Esters; D008074:Lipoproteins; D010743:Phospholipids; D007862:Phosphatidylcholine-Sterol O-Acyltransferase