Hydrolysis and transesterification of platelet-activating factor by lecithin-cholesterol acyltransferase.

Abstract

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.

Atorvastatin Preferentially Reduces LDL-Associated Platelet-Activating Factor Acetylhydrolase Activity in Dyslipidemias of Type IIA and Type IIB

“…32 The antiatherogenic role of HDL-PAF-AH is further supported by recent studies in apoE-deficient mice. 33,34 Besides PAF-AH, 2 other HDL-associated enzymes, lecithin-cholesterol acyltransferase 35 and PON1, 14 exhibit PAF-AH-like activity; thus, the HDL-associated PAF-AH activity may represent a pool of similar catalytic activities expressed by 3 different enzymes. In this context, it has recently been shown that there is no PAF-AH protein in HDL, suggesting that the PAF-AH protein may not contribute to the HDL-associated PAF-AH activity.…”

Hepatic regulation of platelet-activating factor acetylhydrolase and lecithin: Cholesterol acyltransferase biliary and plasma output in rats exposed to bacterial lipopolysaccharide

“…The biological significance of a rapid decrease of LCAT in bile is not clear at present, particularly because we are not yet able to measure the separate contribution of LCAT toward PAF hydrolysis without purifying the enzyme from bile. Liu and Subbaiah 34 have shown that the LCAT purified from plasma exhibits a specific activity toward PAF hydrolysis approximately 10 times lower than toward cholesterol esterification. The present data indicate that the specific activity of bile toward cholesterol esterification is nearly 100 times less than toward PAF hydrolysis and disappeared during the observation period, whereas PAF-AH activity was increased (Figs.…”

Lysophosphatidylcholine Is Involved in the Antigenicity of Oxidized LDL

“…13 One of the active components of oxLDL is LPC, which may be formed during oxidation of LDL 14 or from PC by enzymes with PLA 2 activity. 15 Recently we identified secretory PLA 2 type II (ie, sPLA2-II, nonpancreatic type) expression and activity in both normal and atherosclerotic arterial walls, being mainly expressed by medial smooth muscle cells. 16 This finding opens the possibility that significant amounts of LPC may be generated in the arterial wall by hydrolysis of phospholipids in retained LDL.…”