Lysophosphatidylcholine is Generated by Spontaneous Deacylation of Oxidized Phospholipids

• Published in: Chemical research in toxicology 2011-01, Vol.24 (1), p.111-118
• Main Authors: Choi, Jaewoo, Zhang, Wujuan, Gu, Xiaodong, Chen, Xi, Hong, Li, Laird, James M, Salomon, Robert G
• Format: Article
• Language: English
• Subjects: 1-Alkyl-2-acetylglycerophosphocholine Esterase - antagonists & inhibitors; 1-Alkyl-2-acetylglycerophosphocholine Esterase - metabolism; Catalysis; Chromatography, High Pressure Liquid; Hydrogen-Ion Concentration; Hydrolysis; Lipoproteins, LDL - chemistry; Lipoproteins, LDL - metabolism; Lysophosphatidylcholines - chemistry; Lysophosphatidylcholines - metabolism; Mass Spectrometry; Oxidation-Reduction; Phosphatidylcholines - chemistry; Temperature
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/tx100305b

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) A2 that exists in plasma largely in association with LDL. Drugs that aim to prevent the generation of lysoPC by inhibiting this PLA2-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.