Recent progress on acyl CoA: lysophospholipid acyltransferase research

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. 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. Lipids play essential roles in living system (1van Meer G. Voelker D.R. Feigenson G.W. Membrane lipids: where they are and how they behave.Nat. Rev. Mol. Cell Biol. 2008; 9: 112-124Crossref PubMed Scopus (4618) Google Scholar, 2Shimizu T. Lipid mediators in health and disease: enzymes and receptors as therapeutic targets for the regulation of immunity and inflammation.Annu. Rev. Pharmacol. 2009; 49: 123-150Crossref Scopus (422) Google Scholar). Glycerophospholipids are important structural and functional components of biological membranes and constituents of serum lipoproteins and the pulmonary surfactant. Additionally, glycerophospholipids play important roles as precursors of lipid mediators such as platelet-activating factor (PAF) and eicosanoids (2Shimizu T. Lipid mediators in health and disease: enzymes and receptors as therapeutic targets for the regulation of immunity and inflammation.Annu. Rev. Pharmacol. 2009; 49: 123-150Crossref Scopus (422) Google Scholar, 3Ishii S. Shimizu T. Platelet-activating factor (Paf) receptor and genetically engineered Paf receptor mutant mice.Prog. Lipid Res. 2000; 39: 41-82Crossref PubMed Scopus (330) Google Scholar). In each tissue, cellular membranes contain a distinct composition of various glycerophospholipids (1van Meer G. Voelker D.R. Feigenson G.W. Membrane lipids: where they are and how they behave.Nat. Rev. Mol. Cell Biol. 2008; 9: 112-124Crossref PubMed Scopus (4618) Google Scholar, 4Yamashita A. Sugiura T. Waku K. Acyltransferases and transacylases involved in fatty acid remodeling of phospholipids and metabolism of bioactive lipids in mammalian cells.J Biochem. 1997; 122: 1-16Crossref PubMed Scopus (239) Google Scholar, 5Schlame M. Rua D. Greenberg M.L. The biosynthesis and functional role of cardiolipin.Prog. Lipid Res. 2000; 39: 257-288Crossref PubMed Scopus (665) Google Scholar). The acyl groups of glycerophospholipids are highly diverse, depending on the polar head group, and are distributed in an asymmetric manner (4Yamashita A. Sugiura T. Waku K. Acyltransferases and transacylases involved in fatty acid remodeling of phospholipids and metabolism of bioactive lipids in mammalian cells.J Biochem. 1997; 122: 1-16Crossref PubMed Scopus (239) Google Scholar, 6Lands W.E. Stories about acyl chains.Biochim. Biophys. Acta. 2000; 1483: 1-14Crossref PubMed Scopus (126) Google Scholar). Saturated and monounsaturated fatty acids are usually esterified at the sn-1 position, whereas polyunsaturated acyl groups are esterified at the sn-2 position, although several atypical distributions have been reported (1van Meer G. Voelker D.R. Feigenson G.W. Membrane lipids: where they are and how they behave.Nat. Rev. Mol. Cell Biol. 2008; 9: 112-124Crossref PubMed Scopus (4618) Google Scholar, 2Shimizu T. Lipid mediators in health and disease: enzymes and receptors as therapeutic targets for the regulation of immunity and inflammation.Annu. Rev. Pharmacol. 2009; 49: 123-150Crossref Scopus (422) Google Scholar, 4Yamashita A. Sugiura T. Waku K. Acyltransferases and transacylases involved in fatty acid remodeling of phospholipids and metabolism of bioactive lipids in mammalian cells.J Biochem. 1997; 122: 1-16Crossref PubMed Scopus (239) Google Scholar, 6Lands W.E. Stories about acyl chains.Biochim. Biophys. Acta. 2000; 1483: 1-14Crossref PubMed Scopus (126) Google Scholar, 7Shindou H. Shimizu T. Acyl-CoA: lysophospholipid acyltransferases.J. Biol. Chem. 2009; 284: 1-5Abstract Full Text Full Text PDF PubMed Scopus (322) Google Scholar). Using acyl-CoAs, glycerophospholipids are first synthesized from glycerol-3-phosphate in the de novo pathway, originally described by Kennedy and Weiss in 1956 (Kennedy pathway) (8Kennedy E.P. Weiss S.B. The function of cytidine coenzymes in the biosynthesis of phospholipides.J. Biol. Chem. 1956; 222: 193-214Abstract Full Text PDF PubMed Google Scholar), and undergo maturation in the remodeling pathway, as reported by Lands in 1958 (Lands' cycle) (Fig. 1) (9Lands W.E. Metabolism of glycerolipides; a comparison of lecithin and triglyceride synthesis.J. Biol. Chem. 1958; 231: 883-888Abstract Full Text PDF PubMed Google Scholar). Rapid turnover of the sn-2 acyl moiety of glycerophospholipids is attributed to the concerted and coordinated actions of phospholipase A2s (PLA2s) and lysophospholipid acyltransferases (LPLATs) (Fig. 1) (2Shimizu T. Lipid mediators in health and disease: enzymes and receptors as therapeutic targets for the regulation of immunity and inflammation.Annu. Rev. Pharmacol. 2009; 49: 123-150Crossref Scopus (422) Google Scholar, 6Lands W.E. Stories about acyl chains.Biochim. Biophys. Acta. 2000; 1483: 1-14Crossref PubMed Scopus (126) Google Scholar, 7Shindou H. Shimizu T. Acyl-CoA: lysophospholipid acyltransferases.J. Biol. Chem. 2009; 284: 1-5Abstract Full Text Full Text PDF PubMed Scopus (322) Google Scholar, 10Waku K. Nakazawa Y. Acyltransferae activity to 1-acyl-, 1-o-alkenyl-, and 1-o-alkyl-glycero-3-phosphorylcholine in ehrlich ascites tumor cells.J Biochem. 1972; 72: 495-497Crossref PubMed Scopus (18) Google Scholar). Because there are many species of glycerophospholipids differing in the phosphoryl head groups and the fatty acids in chain lengths and degrees of saturation, many LPLATs should exist. Even though these pathways occur in almost all tissues, in the 50 years since Lands' proposal, there has been no information available on acyltransferases involved in phospholipid remodeling. Recently, several LPLATs have been cloned and characterized by several laboratories, including ours (7Shindou H. Shimizu T. Acyl-CoA: lysophospholipid acyltransferases.J. Biol. Chem. 2009; 284: 1-5Abstract Full Text Full Text PDF PubMed Scopus (322) Google Scholar). In this review, we summarize recent research on the cloning and characterization of the remodeling enzymes. In the de novo pathway of glycerophospholipid biosynthesis, lysophosphatidic acid (LPA) is first formed from glycerol-3-phosphate (GP) by glycerol-3-phosphate acyltransferases (GPAT)s (11Van den Bosch H. DE V. Phospholipid biosynthesis; current status of the Kennedy and related pathways.Biochim. Biophys. Acta. 1997; 1348: 1-2Crossref Google Scholar, 12Coleman R.A. Lee D.P. Enzymes of triacylglycerol synthesis and their regulation.Prog. Lipid Res. 2004; 43: 134-176Crossref PubMed Scopus (723) Google Scholar). LPA is then converted to phosphatidic acid (PA) by lyso-PA acyltransferases (LPAATs), and two types of glycerol derivatives are generated from PA (11Van den Bosch H. DE V. Phospholipid biosynthesis; current status of the Kennedy and related pathways.Biochim. Biophys. Acta. 1997; 1348: 1-2Crossref Google Scholar, 12Coleman R.A. Lee D.P. Enzymes of triacylglycerol synthesis and their regulation.Prog. Lipid Res. 2004; 43: 134-176Crossref PubMed Scopus (723) Google Scholar). One is diacylglycerol, which is subsequently converted to triacylglycerol, phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Some of them are changed into phosphatidylserine (PS). The other glycerol derivative is cytidine diphosphate diacylglycerol, which is modified to form phosphatidylinositol (PI), phosphatidylglycerol (PG), and cardiolipin (CL), or PS. Many key enzymes in the de novo pathways have been characterized, and more detailed information is available in several recent reviews (1van Meer G. Voelker D.R. Feigenson G.W. Membrane lipids: where they are and how they behave.Nat. Rev. Mol. Cell Biol. 2008; 9: 112-124Crossref PubMed Scopus (4618) Google Scholar, 11Van den Bosch H. DE V. Phospholipid biosynthesis; current status of the Kennedy and related pathways.Biochim. Biophys. Acta. 1997; 1348: 1-2Crossref Google Scholar, 12Coleman R.A. Lee D.P. Enzymes of triacylglycerol synthesis and their regulation.Prog. Lipid Res. 2004; 43: 134-176Crossref PubMed Scopus (723) Google Scholar). Several GPATs and LPAATs have been identified from the 1-acylglycerol-3-phophate O-acyltransferase (AGPAT) family, which possess AGPAT motifs (LPLAT motifs) (13Lewin T.M. Wang P. Coleman R.A. Analysis of amino acid motifs diagnostic for the sn-glycerol-3-phosphate acyltransferase reaction.Biochemistry. 1999; 38: 5764-5771Crossref PubMed Scopus (233) Google Scholar, 14Yamashita A. Nakanishi H. Suzuki H. Kamata R. Tanaka K. Waku K. Sugiura T. Topology of acyltransferase motifs and substrate specificity and accessibility in 1-acyl-sn-glycero-3-phosphate acyltransferase 1.Biochim. Biophys. Acta. 2007; 1771: 1202-1215Crossref PubMed Scopus (69) Google Scholar, 15Harayama T. Shindou H. Ogasawara R. Suwabe A. Shimizu T. Identification of a novel noninflammatory biosynthetic pathway of platelet-activating factor.J. Biol. Chem. 2008; 283: 11097-11106Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar). Due to the fact that several groups have cloned LPLATs independently, each enzyme has multiple names. To eliminate confusion in the nomenclature, we propose that the enzymes should be renamed based on their substrate specificities and by the order in which their cloning was reported (Fig. 2) (7Shindou H. Shimizu T. Acyl-CoA: lysophospholipid acyltransferases.J. Biol. Chem. 2009; 284: 1-5Abstract Full Text Full Text PDF PubMed Scopus (322) Google Scholar). We will briefly summarize the acyltransferases involved in the de novo pathway. From the AGPAT family, four mammalian GPATs, which synthesize LPA from GP, have been cloned (Fig. 2). GPAT1 and GPAT2 (also called xGPAT) are located in the outer mitochondrial membrane, whereas GPAT3 (also called AGPAT8, AGPAT9, or LPAATθ) and GPAT4 (also called AGPAT6 or LPAATζ) are localized to the endoplasmic reticulum (ER). These enzymes prefer saturated and monounsaturated fatty acyl-CoAs. The microsomal GPATs are thought to play vital roles in triacylglycerol synthesis. The mitochondrial GPATs are regulated nutritionally and hormonally (12Coleman R.A. Lee D.P. Enzymes of triacylglycerol synthesis and their regulation.Prog. Lipid Res. 2004; 43: 134-176Crossref PubMed Scopus (723) Google Scholar). A recent review described the cloning of GPATs (7Shindou H. Shimizu T. Acyl-CoA: lysophospholipid acyltransferases.J. Biol. Chem. 2009; 284: 1-5Abstract Full Text Full Text PDF PubMed Scopus (322) Google Scholar). PA is synthesized from LPA by LPAAT. Two LPAATs (LPAAT1 and 2) have currently been cloned and characterized (Fig. 2). Human LPAAT1 (also called AGPAT1 or LPAATα) and human LPAAT2 (also called AGPAT2 or LPAATβ) were cloned based on their homologies with yeast, E. coli, and coconut AGPATs. Both mRNAs are found in most tissues. Human LPAAT1 shows higher activity toward 14:0-, 16:0-, and 18:2-CoAs, while human LPAAT2 prefers 20:4-CoA over 16:0- or 18:0-CoA. The AGPAT motifs have been well characterized using GPAT1, LPAAT1, and lyso-PC acyltransferase 1 (LPCAT1, described later). Taken together, these reports indicate that the AGPAT motifs contain the sequences and (13Lewin T.M. Wang P. Coleman R.A. Analysis of amino acid motifs diagnostic for the sn-glycerol-3-phosphate acyltransferase reaction.Biochemistry. 1999; 38: 5764-5771Crossref PubMed Scopus (233) Google Scholar, 14Yamashita A. Nakanishi H. Suzuki H. Kamata R. Tanaka K. Waku K. Sugiura T. Topology of acyltransferase motifs and substrate specificity and accessibility in 1-acyl-sn-glycero-3-phosphate acyltransferase 1.Biochim. Biophys. Acta. 2007; 1771: 1202-1215Crossref PubMed Scopus (69) Google Scholar, 15Harayama T. Shindou H. Ogasawara R. Suwabe A. Shimizu T. Identification of a novel noninflammatory biosynthetic pathway of platelet-activating factor.J. Biol. Chem. 2008; 283: 11097-11106Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar). The amino acids in in motifs 1 and are not LPLATs and of a by amino has that these motifs are important for activity (13Lewin T.M. Wang P. Coleman R.A. Analysis of amino acid motifs diagnostic for the sn-glycerol-3-phosphate acyltransferase reaction.Biochemistry. 1999; 38: 5764-5771Crossref PubMed Scopus (233) Google Scholar, 14Yamashita A. Nakanishi H. Suzuki H. Kamata R. Tanaka K. Waku K. Sugiura T. Topology of acyltransferase motifs and substrate specificity and accessibility in 1-acyl-sn-glycero-3-phosphate acyltransferase 1.Biochim. Biophys. Acta. 2007; 1771: 1202-1215Crossref PubMed Scopus (69) Google Scholar, 15Harayama T. Shindou H. Ogasawara R. Suwabe A. Shimizu T. Identification of a novel noninflammatory biosynthetic pathway of platelet-activating factor.J. Biol. Chem. 2008; 283: 11097-11106Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar). also has activity and synthesis in the remodeling in A recent review described the cloning of LPAATs (7Shindou H. Shimizu T. Acyl-CoA: lysophospholipid acyltransferases.J. Biol. Chem. 2009; 284: 1-5Abstract Full Text Full Text PDF PubMed Scopus (322) Google Scholar). other LPAATs and also called and have been reported as but their toward were (Fig. 2) Y. and characterization of acyltransferases and their regulation by in PubMed Scopus Google Scholar). Additionally, although the is as a acyltransferase in the no characterization has been and a human has not been found (Fig. 2). These have not been in Kennedy and Weiss (8Kennedy E.P. Weiss S.B. The function of cytidine coenzymes in the biosynthesis of phospholipides.J. Biol. Chem. 1956; 222: 193-214Abstract Full Text PDF PubMed Google first reported that phospholipids are synthesized in the de novo pathway (Kennedy and then Lands reported that fatty acyl composition at the sn-2 is in the remodeling pathway (Lands' cycle) the concerted actions of and LPLATs (Fig. 1) (2Shimizu T. Lipid mediators in health and disease: enzymes and receptors as therapeutic targets for the regulation of immunity and inflammation.Annu. Rev. Pharmacol. 2009; 49: 123-150Crossref Scopus (422) Google Scholar, 6Lands W.E. Stories about acyl chains.Biochim. Biophys. Acta. 2000; 1483: 1-14Crossref PubMed Scopus (126) Google Scholar, 7Shindou H. Shimizu T. Acyl-CoA: lysophospholipid acyltransferases.J. Biol. Chem. 2009; 284: 1-5Abstract Full Text Full Text PDF PubMed Scopus (322) Google Scholar). of has been more (2Shimizu T. Lipid mediators in health and disease: enzymes and receptors as therapeutic targets for the regulation of immunity and inflammation.Annu. Rev. Pharmacol. 2009; 49: 123-150Crossref Scopus (422) Google that of Recently, several LPLATs have been cloned and characterized as remodeling enzymes (7Shindou H. Shimizu T. Acyl-CoA: lysophospholipid acyltransferases.J. Biol. Chem. 2009; 284: 1-5Abstract Full Text Full Text PDF PubMed Scopus (322) Google Scholar). is the known glycerophospholipid and four fatty acyl acyltransferase from and Y. P. Y. A novel pathway by a an endoplasmic acyltransferase in Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus Google identified (also called and in the AGPAT and the and of the with a for and (Fig. 2). is with the in the and and are more in the mitochondrial while is localized to the is from the to to be as the specificity of the enzymes. remodeling is to play an important role in the of In is with a by of acyltransferase that as and M. A. T. S. Phospholipid in with PubMed Scopus Google Scholar). In the de novo pathway, is synthesized from which is also a of the family, including the is a of Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). is modified by acyltransferase in the remodeling pathway. Human was the first cloned and shows a for and as with the composition of in several (Fig. 2) Y. Y. Identification and characterization of a human an endoplasmic Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). is distributed in and is localized to the the of these two reports of the cloning of and of acyltransferases in the remodeling pathway have has and activity and the synthesis of and (Fig. 2) H. Shindou H. D. T. Ogasawara R. Suwabe A. R. Shimizu T. and characterization of acyltransferase 1 in and in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, M.L. Identification and characterization of a acyltransferase in PubMed Scopus Google Scholar). These play an important role in function the for acyltransferase (also called or also shows but an for not the activity for (Fig. 2) D. T. D. of a novel mammalian of acyltransferase with lysophospholipid Biol. Chem. 2008; 283: Full Text Full Text PDF PubMed Scopus Google Scholar). enzymes with activity have been identified (Fig. 2) H. Shindou H. D. T. Ogasawara R. Suwabe A. R. Shimizu T. and characterization of acyltransferase 1 in and in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, M.L. Identification and characterization of a acyltransferase in PubMed Scopus Google Scholar, D. T. D. of a novel mammalian of acyltransferase with lysophospholipid Biol. Chem. 2008; 283: Full Text Full Text PDF PubMed Scopus Google Scholar, H. D. Nakanishi H. T. S. R. Shimizu T. A enzyme platelet-activating factor and membrane of cells. cloning and characterization of Biol. Chem. 2007; Full Text Full Text PDF PubMed Scopus Google Scholar, D. Shindou H. S. Nakanishi H. R. Shimizu T. of a lysophospholipid acyltransferase essential for membrane asymmetry and 2008; PubMed Scopus Google Scholar, Y. T.M. S. M. G. Identification and characterization of a Biol. Chem. 2008; 283: Full Text Full Text PDF PubMed Scopus Google Scholar, S. T. Lee Tanaka S. H. of the a lysophospholipid acyltransferase with substrate 2008; PubMed Scopus Google Scholar). and are of the AGPAT family, whereas and are of a acyltransferase family, the membrane bound O-acyltransferase (MBOAT) family. We and H. Shindou H. D. T. Ogasawara R. Suwabe A. R. Shimizu T. and characterization of acyltransferase 1 in and in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, M.L. Identification and characterization of a acyltransferase in PubMed Scopus Google (also called or which and synthesis (Fig. 2). is in the in and was the phospholipids are components of the pulmonary lipids, which and is essential for to the of lipids and R.A. 2007; Full Text Full Text PDF PubMed Scopus Google Scholar). The of and with acid or acid at the sn-2 or as in H. Shindou H. D. T. Ogasawara R. Suwabe A. R. Shimizu T. and characterization of acyltransferase 1 in and in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). synthesize most of the phospholipids in the pulmonary and play a role in are to the and lipid synthesis. We identified (also called or which and synthesis in (Fig. 2) H. D. Nakanishi H. T. S. R. Shimizu T. A enzyme platelet-activating factor and membrane of cells. cloning and characterization of Biol. Chem. 2007; Full Text Full Text PDF PubMed Scopus Google Scholar). two types of glycerophospholipids and are synthesized from the using a enzyme H. D. Nakanishi H. T. S. R. Shimizu T. A enzyme platelet-activating factor and membrane of cells. cloning and characterization of Biol. Chem. 2007; Full Text Full Text PDF PubMed Scopus Google Scholar). is in by with receptor but the is by with the activity of was in the pathway, with the of activity H. S. M. K. S. Shimizu T. of on factor is and PubMed Scopus Google Scholar). In the activity of was not H. D. Nakanishi H. T. S. R. Shimizu T. A enzyme platelet-activating factor and membrane of cells. cloning and characterization of Biol. Chem. 2007; Full Text Full Text PDF PubMed Scopus Google Scholar). a enzyme membrane acyltransferase of while in to the two are regulated to be of be receptor to the fact that such of by membrane in to the by We reported that also a activity (Fig. 2) T. Shindou H. Ogasawara R. Suwabe A. Shimizu T. Identification of a novel noninflammatory biosynthetic pathway of platelet-activating factor.J. Biol. Chem. 2008; 283: 11097-11106Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar). In the amino acid of that are essential for each activity or were identified by In to was by in the activity is activity is These indicate two distinct remodeling pathways for the and the remodeling pathway T. Shindou H. Ogasawara R. Suwabe A. Shimizu T. Identification of a novel noninflammatory biosynthetic pathway of platelet-activating factor.J. Biol. Chem. 2008; 283: 11097-11106Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar). The and is to that of 1 and which are and R. there are two PubMed Scopus Google Scholar). is that other is as is in cells. also shows but an for not the activity for (Fig. 2) D. T. D. of a novel mammalian of acyltransferase with lysophospholipid Biol. Chem. 2008; 283: Full Text Full Text PDF PubMed Scopus Google Scholar). In was reported to activity in although the activity was E. H. acyltransferase 2008; PubMed Scopus Google Scholar). We and D. Shindou H. S. Nakanishi H. R. Shimizu T. of a lysophospholipid acyltransferase essential for membrane asymmetry and 2008; PubMed Scopus Google Scholar, Y. T.M. S. M. G. Identification and characterization of a Biol. Chem. 2008; 283: Full Text Full Text PDF PubMed Scopus Google identified in the family, which acyltransferase acyltransferases 1 and and such as acyltransferase (2Shimizu T. Lipid mediators in health and disease: enzymes and receptors as therapeutic targets for the regulation of immunity and inflammation.Annu. Rev. Pharmacol. 2009; 49: 123-150Crossref Scopus (422) Google Scholar, 7Shindou H. Shimizu T. Acyl-CoA: lysophospholipid acyltransferases.J. Biol. Chem. 2009; 284: 1-5Abstract Full Text Full Text PDF PubMed Scopus (322) Google Scholar, K. A of with for Biochem. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). (also called and acyltransferase (Fig. 2) D. Shindou H. S. Nakanishi H. R. Shimizu T. of a lysophospholipid acyltransferase essential for membrane asymmetry and 2008; PubMed Scopus Google Scholar, Y. T.M. S. M. G. Identification and characterization of a Biol. Chem. 2008; 283: Full Text Full Text PDF PubMed Scopus Google Scholar, S. T. Lee Tanaka S. H. of the a lysophospholipid acyltransferase with substrate 2008; PubMed Scopus Google Scholar). the is a novel family. was and higher acyltransferase activity toward polyunsaturated fatty acyl-CoAs, 20:4-CoA and saturated fatty acyl-CoAs. with into and with 20:4-CoA and the of and containing arachidonic acid at the sn-2 called and with a for (Fig. 2) D. Shindou H. S. Nakanishi H. R. Shimizu T. of a lysophospholipid acyltransferase essential for membrane asymmetry and 2008; PubMed Scopus Google Scholar). is highly in the and Because and higher activity with or as these enzymes the the and at the sn-1 of D. Shindou H. S. Nakanishi H. R. Shimizu T. of a lysophospholipid acyltransferase essential for membrane asymmetry and 2008; PubMed Scopus Google Scholar). (also called is a of the and and with a for (Fig. 2) D. Shindou H. S. Nakanishi H. R. Shimizu T. of a lysophospholipid acyltransferase essential for membrane asymmetry and 2008; PubMed Scopus Google Scholar). is highly in the and and also have toward polyunsaturated acyl-CoAs and In to the of and no were the and of each and synthesis in the remodeling pathway (Fig. 2). polyunsaturated acyl-CoAs and prefers in the of and containing polyunsaturated fatty acids at the sn-2 In and and and acid to the sn-2 of D. Shindou H. S. Nakanishi H. R. Shimizu T. of a lysophospholipid acyltransferase essential for membrane asymmetry and 2008; PubMed Scopus Google Scholar). Recently, called or was identified from the AGPAT D. T. D. of a novel mammalian of acyltransferase with lysophospholipid Biol. Chem. 2008; 283: Full Text Full Text PDF PubMed Scopus Google Scholar). The enzyme is to and and and toward or 20:4-CoA (Fig. 2). an for the but not the or in D. T. D. of a novel mammalian of acyltransferase with lysophospholipid Biol. Chem. 2008; 283: Full Text Full Text PDF PubMed Scopus Google Scholar). Due to the fact that was in the play roles in the of acyltransferase (also called and is the first enzyme in the remodeling pathway to be identified T. R. S. S. S. H. a of the family, is for of polyunsaturated fatty acids into Biol. 2008; PubMed Scopus Google (Fig. 2). activity toward 20:4-CoA and the of human a a mutant of and possess more are the constituents of biological important roles in the of the cellular and the regulation of cellular Kennedy and Lands reported the synthesis of phospholipids in the de novo pathway (Kennedy and the maturation of phospholipids in the remodeling pathway (Lands' cycle), to membrane (Fig. Membrane is important for membrane and and is by the concerted and of multiple LPLATs that the polar head groups of and various acyl-CoAs in the remodeling pathway. In the many LPLATs in the remodeling pathway have been in the most in the since the of the Kennedy pathway and the Lands' cycle 50 years (2Shimizu T. Lipid mediators in health and disease: enzymes and receptors as therapeutic targets for the regulation of immunity and inflammation.Annu. Rev. Pharmacol. 2009; 49: 123-150Crossref Scopus (422) Google Scholar, 7Shindou H. Shimizu T. Acyl-CoA: lysophospholipid acyltransferases.J. Biol. Chem. 2009; 284: 1-5Abstract Full Text Full Text PDF PubMed Scopus (322) Google Scholar). each enzyme has several and each to several we have proposed LPLATs in order to and the 2) (7Shindou H. Shimizu T. Acyl-CoA: lysophospholipid acyltransferases.J. Biol. Chem. 2009; 284: 1-5Abstract Full Text Full Text PDF PubMed Scopus (322) Google Scholar). Identification of LPLATs contribute to of membrane and will be to how many enzymes are and to over species of