Submitted on June 13, 2007
Revised on July 10, 2007
Accepted on July 11, 2007
The acylation of lipophilic alcohols by lysosomal phospholipase A2
Akira Abe, Miki Hiraoka, and James A. Shayman
Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109-0676
Corresponding Author: jshayman{at}umich.edu
A novel lysosomal phospholipase A2 with specificity toward phosphatidylethanolamine and phosphatidylcholine was previously purified, cloned and named lysosomal phospholipase A2 (LPLA2). LPLA2 transfers sn-1 or sn-2 acyl groups of phospholipids to the C1 hydroxyl of the short chain ceramide N-acetylsphingosine (NAS) under acidic conditions. The common features of lipophilic alcohols serving as acceptor molecules in the transacylase reaction were examined. 1-O-Hexadecyl-2-acetyl-sn-glycerol (HAG) was acylated by LPLA2 in similar to NAS. HAG competed with NAS and inhibited NAS acylation. The transacylation of 1-O-hexadecyl-glycerol (HG), 1-O-palmityl-2-O-methyl-sn-glycerol (PMG) and monoacylglycerols was also investigated. HG, PMG, 1- or 3-palmitoyl-sn-glycerol and 2-palmitoylglycerol were converted to 1,3-alkylacylglycerol, 1,2-dialkyl-3-acylglycerol, 1,3-diacylglycerol and 1,2- or 2,3-diacylglycerol, respectively. HG and monoacylglycerol inhibited the acylation of NAS by the enzyme with IC50s of 35 µM and 45 µM, respectively. Additionally, the enzyme acylated glycerol to produce 1- or 3-acyl-sn-glycerol but not 2-acylglycerol. Therefore the preferred acceptor molecules for LPLA2 are primary alcohols with one long carbon chain and one small non-polar residue linked to the C2 position of ethanol. The enzyme acylated other natural lipophilic alcohols, including anandamide and oleoylethanolamide. Thus LPLA2 may function to remodel acyl groups of and modulate the biological and pharmacological activities of some lipophilic alcohols.
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