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Journal of Lipid Research, Vol. 50, S46-S51, April 2009
Recent progress on acyl CoA: lysophospholipid acyltransferase research
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan This work was supported in part by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (T.S.) and a Global COE Program (The University of Tokyo) from the Japan Society for Promotion of Sciences (T.S.). T.S. and H.S. were supported by the Center for NanoBio Integration at The University of Tokyo. H.S. was supported by Health and Labour Sciences Research Grants (Research on Allergic Disease and Immunology) supported by the Ministry of Health, Labour, and Welfare of Japan, the Mitsubishi Pharma Research Foundation, and the Ono Medical Research Foundation. Published, JLR Papers in Press, October 17, 2008.
1 To whom correspondence should be addressed. e-mail: hshindou-tky{at}umin.ac.jp
Cells of all organisms are enclosed by a plasma membrane containing bipolar lipids, cholesterol, and proteins. Cellular membranes contain several classes of glycerophospholipids, which have numerous structural and functional roles in cells. Polyunsaturated fatty acids including arachidonic acid and eicosapentaenoic acid are usually located at the sn-2 position, but not the sn-1 position, of glycerophospholipids in an asymmetrical manner. Glycerophospholipids are first formed by the de novo pathway (Kennedy pathway) using acyl-CoAs as donors. Subsequently, in the remodeling pathway (Lands' cycle), cycles of deacylation and reacylation of glycerophospholipids modify the fatty acid composition to generate mature membrane with asymmetry and diversity. Both pathways were proposed in the 1950s. Whereas the enzymes involved in the Kennedy pathway have been well characterized, little is known about the enzymes involved in the Lands' cycle. Recently, several laboratories, including ours, have identified enzymes working in the Lands' cycle from the 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) family, and also from the membrane bound O-acyltransferases (MBOAT) family. These discoveries have prompted a robust surge of research in this field. In this review, we focus on the cloning and characterization of lysophospholipid acyltransferases (LPLATs), which contribute to membrane asymmetry and diversity.
Supplementary key words Lands' cycle LPLAT membrane diversity membrane asymmetry glycerophospholipid platelet-activating factor MBOAT AGPAT remodeling pathway surfactant lipid Abbreviations: AGPAT, 1-acylglycerol-3-phophate O-acyltransferase; CL, cardiolipin; GP, glycerol-3-phosphate; GPAT, GP acyltransferase; LCLAT, lyso-CL acyltransferase; LPA, lysophosphatidic acid; LPAAT, lyso-PA acyltransferase; LPCAT, lyso-PC acyltransferase; LPEAT, lyso-PE acyltransferase; LPGAT, lyso-PG acyltransferase; LPIAT, lyso-PI acyltransferase; LPLAT, lysophospholipid acyltransferase; LPSAT, lyso-PS acyltransferase; MBOAT, membrane bound O-acyltransferase; PA, phosphatidic acid; PAF, platelet-activating factor; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PI, phosphatidylinositol; PG, phosphatidylglycerol; PLA2, phospholipase A2; PS, phosphatidylserine
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