Lysophosphatidylcholine is Generated by Spontaneous Deacylation of Oxidized Phospholipids

Overview

Journal Chem Res Toxicol

Publisher American Chemical Society

Specialty Toxicology

Date 2010 Oct 27

PMID 20973507

Citations 37

Authors

Jaewoo Choi

Wujuan Zhang

Xiaodong Gu

Xi Chen

Li Hong

James M Laird

Robert G Salomon

Affiliations

Soon will be listed here.

Abstract

Elevated levels of lysophosphatidylcholine (lysoPC), present in oxidatively damaged low-density lipoprotein (oxLDL), are implicated in cardiovascular complications. LysoPC is generated by free radical-catalyzed oxidation of polyunsaturated PCs to oxidatively truncated phosphophatidylcholines (oxPCs). It is known that oxPCs are especially susceptible to hydrolysis by platelet-activating factor acetylhydrolase, a phospholipase (PL) A(2) that exists in plasma largely in association with LDL. Drugs that aim to prevent the generation of lysoPC by inhibiting this PLA(2)-catalyzed hydrolysis are in advanced clinical trials. We now report that spontaneous deacylation oxPCs, such as 1-palmityl-2-(4-hydroxy-7-oxo-5-heptenoyl)-sn-glycero-3-phosphocholine, occurs readily under physiological conditions of temperature and pH (t(1/2) = 30 min at 37 °C and pH 7.4). We also show that this reaction proceeds through an intramolecular transesterification mechanism. Because antiphospholipase drugs cannot block this nonenzymatic pathway to lysoPC, additional therapeutic measures may be needed to avoid the pathological consequences of the newly discovered biomolecular chemistry of oxPCs.

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