Hydrolysis and transesterification of platelet-activating factor by lecithin-cholesterol acyltransferase.
Purified lecithin-cholesterol acyltransferase (LCAT, EC 2.3.1.43) from human plasma was found to hydrolyze platelet-activating factor (PAF) to lyso-PAF and acetate. In addition, it catalyzed the transfer of the acetate group from PAF to lysophosphatidylcholine, forming lyso-PAF and a 1-acyl analog of PAF. In contrast to the cholesterol-esterification reaction carried out by the enzyme, the hydrolysis and transacetylation of PAF by LCAT did not require an apoprotein activator and were not inhibited by sulfhydryl inhibitors but were inhibited by serum albumin. When added to a proteoliposome substrate of LCAT or to whole plasma, PAF inhibited cholesterol esterification by LCAT competitively. PAF acetylhydrolase (EC 3.1.1.47), purified from human plasma, also catalyzed the transfer of acetate from PAF to lysophosphatidylcholine. However, the LCAT-catalyzed reactions of PAF were not due to contamination with PAF acetylhydrolase, since the ratio of acetyl transfer to acetyl hydrolysis was 3 times greater for LCAT, when compared with PAF acetylhydrolase under identical conditions. Furthermore, recombinant human LCAT secreted by baby hamster kidney cells also catalyzed the hydrolysis and transacetylation of PAF. These results demonstrate that LCAT can inactivate PAF in plasma by transacetylation and suggest that it may have a role in the metabolism of PAF, and possibly of oxidized phospholipids, in plasma.
Department of Medicine, Rush Medical College, Chicago, IL 60612.
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Liu
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Subbaiah
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D016632:Apolipoprotein A-I / Q000302:isolation & purification / Q000378:metabolism; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D004952:Esters; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood* / Q000302:isolation & purification; D010741:Phospholipases A / Q000097:blood* / Q000302:isolation & purification; D010972:Platelet Activating Factor / Q000378:metabolism*; D013997:Time Factors
D016632:Apolipoprotein A-I; D004952:Esters; D010972:Platelet Activating Factor; D004228:Dithionitrobenzoic Acid; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase