Novel function of lecithin-cholesterol acyltransferase. Hydrolysis of oxidized polar phospholipids generated during lipoprotein oxidation.
Although the major function of lecithin-cholesterol acyltransferase (LCAT) is cholesterol esterification, our previous studies showed that it can also hydrolyze platelet-activating factor (PAF). Because of the structural similarities between PAF and the truncated phosphatidylcholines (polar PCs) generated during lipoprotein oxidation, we investigated the possibility that LCAT may also hydrolyze polar PCs to lyso-PC during the oxidation of plasma. PAF acetylhydrolase (PAF-AH), which is known to hydrolyze polar PCs in human plasma, was completely inhibited by 0.2 mM p-aminoethyl benzenesulfonyl fluoride (Pefabloc), a new serine esterase inhibitor, which had no effect on LCAT at this concentration. On the other hand, 1 mM diisopropylfluorophosphate (DFP) completely inhibited LCAT but had no effect on PAF-AH. Polar PC accumulation during the oxidation of plasma increased by 44% in the presence of 0.2 mM Pefabloc and by 30% in the presence of 1 mM DFP. The formation of lyso-PC was concomitantly inhibited by both of the inhibitors. The combination of the two inhibitors resulted in the maximum accumulation of polar PCs, suggesting that both PAF-AH and LCAT are involved in their breakdown. Oxidation of chicken plasma, which has no PAF-AH activity, also resulted in the formation of lyso-PC from the hydrolysis of polar PC, which was inhibited by DFP. Polar PCs, either isolated from oxidized plasma or by oxidation of labeled synthetic PCs, were hydrolyzed by purified LCAT, which had no detectable PAF-AH activity. These results demonstrate a novel function for LCAT in the detoxification of polar PCs generated during lipoprotein oxidation, especially when the PAF-AH is absent or inactivated.
Goyal
J
J
Departments of Medicine and Biochemistry, Rush Medical College, Chicago, Illinois 60612, USA.
Wang
K
K
Liu
M
M
Subbaiah
P V
PV
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000328:Adult; D000818:Animals; D002645:Chickens; D006801:Humans; D006868:Hydrolysis; D007531:Isoflurophate / Q000494:pharmacology; D008074:Lipoproteins / Q000378:metabolism*; D008875:Middle Aged; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors / Q000502:physiology*
D008074:Lipoproteins; D010713:Phosphatidylcholines; D007531:Isoflurophate; D002785:Sterol O-Acyltransferase; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase