2008/08/22 by Hideo Shindou, Takao Shimizu · 28 citations
Biochemistry, Genetics and Molecular Biology · #Lipid metabolism and biosynthesis #Lipid Membrane Structure and Behavior #Sphingolipid Metabolism and Signaling
paper · pdf · doi:10.1074/jbc.r800046200
Cell membranes contain several classes of glycerophospholipids, which have numerous structural and functional roles in the cells. Polyunsaturated fatty acids, including arachidonic acid and eicosapentaenoic acid, are located at the sn-2 (but not sn-1)-position of glycerophospholipids in an asymmetrical manner. Using acyl-CoAs as donors, glycerophospholipids are formed by a de novo pathway (Kennedy pathway) and modified by a remodeling pathway (Lands' cycle) to generate membrane asymmetry and diversity. Both pathways were reported in the 1950s. Whereas enzymes involved in the Kennedy pathway have been well characterized, including enzymes in the 1-acylglycerol-3-phosphate O-acyltransferase family, little is known about enzymes involved in the Lands' cycle. Recently, several laboratories, including ours, isolated enzymes working in the remodeling pathway. These enzymes were discovered not only in the 1-acylglycerol-3-phosphate O-acyltransferase family but also in the membrane-bound O-acyltransferase family. In this review, we summarize recent studies on cloning and characterization of lysophospholipid acyltransferases that contribute to membrane asymmetry and diversity. Cell membranes contain several classes of glycerophospholipids, which have numerous structural and functional roles in the cells. Polyunsaturated fatty acids, including arachidonic acid and eicosapentaenoic acid, are located at the sn-2 (but not sn-1)-position of glycerophospholipids in an asymmetrical manner. Using acyl-CoAs as donors, glycerophospholipids are formed by a de novo pathway (Kennedy pathway) and modified by a remodeling pathway (Lands' cycle) to generate membrane asymmetry and diversity. Both pathways were reported in the 1950s. Whereas enzymes involved in the Kennedy pathway have been well characterized, including enzymes in the 1-acylglycerol-3-phosphate O-acyltransferase family, little is known about enzymes involved in the Lands' cycle. Recently, several laboratories, including ours, isolated enzymes working in the remodeling pathway. These enzymes were discovered not only in the 1-acylglycerol-3-phosphate O-acyltransferase family but also in the membrane-bound O-acyltransferase family. In this review, we summarize recent studies on cloning and characterization of lysophospholipid acyltransferases that contribute to membrane asymmetry and diversity. All organisms are composed of cells that are enclosed by a cell membrane, which contains phospholipids, cholesterol, and proteins. Lipids fulfill four general functions. (i) They serve as an efficient source of energy; (ii) they form cell membranes that contain the bipolar lipids of glycerophospholipids and sphingophospholipids; (iii) they participate in the regulation of particular proteins through post-translational lipid modification; and (iv) they serve as messengers during cellular signal transduction (1.van Meer G. Voelker D.R. Feigenson G.W. Nat. Rev. Mol. Cell Biol. 2008; 9: 112-124Crossref PubMed Scopus (4234) Google Scholar). Thus, glycerophospholipids are important not only as structural and functional components of cell membranes but also as precursors of various lipid mediators, such as PAF 2The abbreviations used are: PAF, platelet-activating factor; PA, phosphatidic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; CL, cardiolipin; PI, phosphatidylinositol; PS, phosphatidylserine; PLA2, phospholipase A2; LPLAT, lysophospholipid acyltransferase; LPA, lysophosphatidic acid; GPAT, glycerol-3-phosphate acyltransferase; LPAAT, LPA acyltransferase; DAG, diacylglycerol; TAG, triacylglycerol; AGPAT, 1-acylglycerol-3-phosphate O-acyltransferase; LCLAT, lyso-CL acetyltransferase; ER, endoplasmic reticulum; LPGAT, lyso-PG acetyltransferase; LPCAT, lyso-PC acyltransferase; TLR, Toll-like receptor; LPEAT, lyso-PE acyltransferase; LPSAT, lyso-PS acyltransferase; MBOAT, membrane-bound O-acyltransferase; LPIAT, lyso-PI acyltransferase. and eicosanoids (2.Ishii S. Shimizu T. Prog. Lipid Res. 2000; 39: 41-82Crossref PubMed Scopus (326) Google Scholar, 3.Shimizu T. Ohto T. Kita Y. IUBMB Life. 2006; 58: 328-333Crossref PubMed Scopus (69) Google Scholar). Each tissue maintains a distinct content and composition of various phospholipids, such as PA, PC, PE, PG, CL, PI, and PS (1.van Meer G. Voelker D.R. Feigenson G.W. Nat. Rev. Mol. Cell Biol. 2008; 9: 112-124Crossref PubMed Scopus (4234) Google Scholar, 4.Yamashita A. Sugiura T. Waku K. J. Biochem. (Tokyo). 1997; 122: 1-16Crossref PubMed Scopus (233) Google Scholar, 5.Schlame M. Rua D. Greenberg M.L. Prog. Lipid Res. 2000; 39: 257-288Crossref PubMed Scopus (651) Google Scholar). For the biosynthesis of glycerophospholipids, fatty acids first need to be activated to acyl-CoAs as described by Kornberg and Pricer (6.Kornberg A. Pricer Jr., W.E. J. Biol. Chem. 1953; 204: 329-343Abstract Full Text PDF PubMed Google Scholar). Using acyl-CoAs as donors, phospholipids are formed from glycerol 3-phosphate by the de novo pathway, originally described by Kennedy and Weiss in 1956 (7.Kennedy E.P. Weiss S.B. J. Biol. Chem. 1956; 222: 193-214Abstract Full Text PDF PubMed Google Scholar). However, the acyl groups of glycerophospholipids are highly diverse and are distributed in an asymmetric manner (4.Yamashita A. Sugiura T. Waku K. J. Biochem. (Tokyo). 1997; 122: 1-16Crossref PubMed Scopus (233) Google Scholar, 8.Lands W.E. Biochim. Biophys. Acta. 2000; 1483: 1-14Crossref PubMed Scopus (120) 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. This diversity and asymmetry is not fully explained by the Kennedy pathway. Rapid turnover of the sn-2-acyl moiety of glycerophospholipids was originally described by Lands as the remodeling pathway (Lands’ cycle) (9.Lands W.E. J. Biol. Chem. 1958; 231: 883-888Abstract Full Text PDF PubMed Google Scholar) and is attributed to the concerted and coordinated actions of PLA2s and LPLATs (3.Shimizu T. Ohto T. Kita Y. IUBMB Life. 2006; 58: 328-333Crossref PubMed Scopus (69) Google Scholar, 8.Lands W.E. Biochim. Biophys. Acta. 2000; 1483: 1-14Crossref PubMed Scopus (120) Google Scholar, 10.Waku K. Nakazawa Y. J. Biochem. (Tokyo). 1972; 72: 495-497Crossref PubMed Scopus (18) Google Scholar). Although these metabolic processes occur in a variety of tissues, information on the enzymes involved in phospholipid remodeling has been lacking for the past 50 years. Dr. Lands asked in his review, “Which enzymes distinguish between saturated and unsaturated acyl chains?” (8.Lands W.E. Biochim. Biophys. Acta. 2000; 1483: 1-14Crossref PubMed Scopus (120) Google Scholar). Now, we may be able to answer that question because several LPLATs have been recently cloned and characterized. In this review, after a brief description of the enzymes of the Kennedy pathway, we will summarize recent findings on the cloning and characterization of remodeling enzymes in the Lands’ cycle. In the de novo pathway of glycerophospholipid biosynthesis, LPA is first formed from glycerol 3-phosphate by GPAT (11.Van den Bosch H. Vance D.E. Biochim. Biophys. Acta. 1997; 1348: 1-2Crossref Google Scholar, 12.Coleman R.A. Lee D.P. Prog. Lipid Res. 2004; 43: 134-176Crossref PubMed Scopus (691) Google Scholar). Next, LPA is converted to PA by LPAATs, and PA is metabolized into two types of glycerol derivatives (11.Van den Bosch H. Vance D.E. Biochim. Biophys. Acta. 1997; 1348: 1-2Crossref Google Scholar, 12.Coleman R.A. Lee D.P. Prog. Lipid Res. 2004; 43: 134-176Crossref PubMed Scopus (691) Google Scholar). One is DAG, which is then converted to TAG, PC, and PE. Subsequently, PS is synthesized from PC or PE. The other glycerol derivative is cytidine diphospho-DAG, which is transformed into PI, PS, PG, and CL (Fig. 1). Several key enzymes in the de novo pathways have been characterized, and additional information is available in other review articles (1.van Meer G. Voelker D.R. Feigenson G.W. Nat. Rev. Mol. Cell Biol. 2008; 9: 112-124Crossref PubMed Scopus (4234) Google Scholar, 11.Van den Bosch H. Vance D.E. Biochim. Biophys. Acta. 1997; 1348: 1-2Crossref Google Scholar, 12.Coleman R.A. Lee D.P. Prog. Lipid Res. 2004; 43: 134-176Crossref PubMed Scopus (691) Google Scholar). Several acyltransferases that form LPA or PA have been identified, and all of them are members of the AGPAT family, which possesses LPLAT motifs (13.Lewin T.M. Wang P. Coleman R.A. Biochemistry. 1999; 38: 5764-5771Crossref PubMed Scopus (224) Google Scholar, 14.Yamashita A. Nakanishi H. Suzuki H. Kamata R. Tanaka K. Waku K. Sugiura T. Biochim. Biophys. Acta. 2007; 1771: 1202-1215Crossref PubMed Scopus (67) Google Scholar). Because several groups independently cloned LPLATs, they have multiple names. For example, AGPAT1 is also called LPAATα, and AGPAT8 is also known as AGPAT9, LPAATθ, or GPAT3. Confusingly, LCLAT1 was also given the name AGPAT8. To eliminate the confusion about the nomenclature, we propose that the enzymes be renamed based on their substrate specificities and by the order of their cloning publications (Table 1).TABLE 1Summary of LPLATs: a proposal for the standardization of LPLAT nomenclature Open table in a new tab GPATs—Four mammalian GPATs have been cloned (15.Yet S.F. Lee S. Hahm Y.T. Sul H.S. Biochemistry. 1993; 32: 9486-9491Crossref PubMed Scopus (76) Google Scholar, 16.Harada N. Hara S. Yoshida M. Zenitani T. Mawatari K. Nakano M. Takahashi A. Hosaka T. Yoshimoto K. Nakaya Y. Mol. Cell. Biochem. 2007; 297: 41-51Crossref PubMed Scopus (29) Google Scholar, 17.Cao J. Li J.L. Li D. Tobin J.F. Gimeno R.E. Proc. Natl. Acad. Sci. U. S. A. 2006; 103: 19695-19700Crossref PubMed Scopus (159) Google Scholar, 18.Chen Y.Q. Kuo M.S. Li S. Bui H.H. Peake D.A. Sanders P.E. Thibodeaux S.J. Chu S. Qian Y.W. Zhao Y. Bredt D.S. Moller D.E. Konrad R.J. Beigneux A.P. Young S.G. Cao G. J. Biol. Chem. 2008; 283: 10048-10057Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar, 19.Nagle C.A. Vergnes L. Dejong H. Wang S. Lewin T.M. Reue K. Coleman R.A. J. Lipid Res. 2008; 49: 823-831Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar). GPAT1 and GPAT2 (also called xGPAT (16.Harada N. Hara S. Yoshida M. Zenitani T. Mawatari K. Nakano M. Takahashi A. Hosaka T. Yoshimoto K. Nakaya Y. Mol. Cell. Biochem. 2007; 297: 41-51Crossref PubMed Scopus (29) Google Scholar)) are located in the outer mitochondrial membrane, whereas GPAT3 (called AGPAT8, AGPAT9, or LPAATθ) and GPAT4 (called AGPAT6 or LPAATζ) are localized to the ER. GPAT1 is resistant to sulfhydryl agents like N-ethylmaleimide and prefers 16:0-CoA as a substrate (12.Coleman R.A. Lee D.P. Prog. Lipid Res. 2004; 43: 134-176Crossref PubMed Scopus (691) Google Scholar). In the liver of GPAT1 knock-out mice, the palmitate (16:0) content was lower at the sn-1-position of TAG, PC, and PE, indicating the important role of the mitochondrial form of GPAT in TAG and glycerophospholipid formation (12.Coleman R.A. Lee D.P. Prog. Lipid Res. 2004; 43: 134-176Crossref PubMed Scopus (691) Google Scholar). GPAT2 is N-ethylmaleimide-sensitive, has no preference for 16:0-CoA, and is expressed mainly in mouse testis (20.Wang S. Lee D.P. Gong N. Schwerbrock N.M. Mashek D.G. Gonzalez-Baro M.R. Stapleton C. Li L.O. Lewin T.M. Coleman R.A. Arch. Biochem. Biophys. 2007; 465: 347-358Crossref PubMed Scopus (67) Google Scholar). The microsomal form of GPAT constitutes ∼90% of the total GPAT activity in most tissues but only 50–80% of the activity in the liver (12.Coleman R.A. Lee D.P. Prog. Lipid Res. 2004; 43: 134-176Crossref PubMed Scopus (691) Google Scholar). Moreover, in differentiating 3T3-L1 adipocytes, the specific activity of microsomal GPAT is 70-fold higher, whereas mitochondrial GPAT activity is only 10-fold higher (12.Coleman R.A. Lee D.P. Prog. Lipid Res. 2004; 43: 134-176Crossref PubMed Scopus (691) Google Scholar). The mRNA level of GPAT3 is consistently 60-fold higher in 3T3-L1 adipocytes than in preadipocytes (17.Cao J. Li J.L. Li D. Tobin J.F. Gimeno R.E. Proc. Natl. Acad. Sci. U. S. A. 2006; 103: 19695-19700Crossref PubMed Scopus (159) Google Scholar). On the other hand, GPAT4 is expressed in many tissues. Both GPAT3 and GPAT4 recognize a broad range of substrates from 12:0-CoA to 18:1- or 18:2-CoA as donors. The microsomal form of GPAT is thought to play vital roles in TAG synthesis. The mitochondrial form of GPAT is regulated nutritionally and hormonally (12.Coleman R.A. Lee D.P. Prog. Lipid Res. 2004; 43: 134-176Crossref PubMed Scopus (691) Google Scholar). LPAATs—GPATs catalyze the formation of LPA from glycerol 3-phosphate, and LPAATs subsequently catalyze the formation of PA from LPA in the de novo pathway. To date, two LPAATs (LPAAT1 and LPAAT2) have been cloned and characterized (21.West J. Tompkins C.K. Balantac N. Nudelman T. S. Coleman J. A. Cell Biol. 1997; PubMed Scopus Google Scholar, K. Biochem. J. 1997; PubMed Scopus Google Scholar, K. Shimizu T. Biochem. Biophys. Res. 1997; PubMed Scopus Google Scholar, C. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google and additional have been reported but have not been in Y. Biochem. J. PubMed Scopus Google Scholar). They are all members of the AGPAT family and have four LPLAT (called AGPAT1 or and (called or were cloned based on their to and (21.West J. Tompkins C.K. Balantac N. Nudelman T. S. Coleman J. A. Cell Biol. 1997; PubMed Scopus Google Scholar, K. Biochem. J. 1997; PubMed Scopus Google Scholar, C. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). is expressed (21.West J. Tompkins C.K. Balantac N. Nudelman T. S. Coleman J. A. Cell Biol. 1997; PubMed Scopus Google Scholar, K. Biochem. J. 1997; PubMed Scopus Google Scholar). higher activity and and 18:1- and D. L. L. L. H. Tompkins C.K. T. J. Lipid Res. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar). The LPLAT motifs of contain the and A. Nakanishi H. Suzuki H. Kamata R. Tanaka K. Waku K. Sugiura T. Biochim. Biophys. Acta. 2007; 1771: 1202-1215Crossref PubMed Scopus (67) Google Scholar). of that these motifs are for activity A. Nakanishi H. Suzuki H. Kamata R. Tanaka K. Waku K. Sugiura T. Biochim. Biophys. Acta. 2007; 1771: 1202-1215Crossref PubMed Scopus (67) Google Scholar). mRNA is in most tissues, the in the and adipocytes (21.West J. Tompkins C.K. Balantac N. Nudelman T. S. Coleman J. A. Cell Biol. 1997; PubMed Scopus Google Scholar, C. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, S. N. A. Nat. PubMed Scopus Google Scholar). prefers than or C. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, D. L. L. L. H. Tompkins C.K. T. J. Lipid Res. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar). in have been to (also known as S. N. A. Nat. PubMed Scopus Google indicating that is involved in TAG and in LPLATs in the AGPAT other LPAATs also called and have been but their activity was Y. Biochem. J. PubMed Scopus Google Scholar). a mouse is in the the were not and a has not been are first synthesized in the de novo pathway, and their fatty acyl composition at the is in the remodeling pathway (Lands' cycle) through the concerted actions of PLA2s and LPLATs (9.Lands W.E. J. Biol. Chem. 1958; 231: 883-888Abstract Full Text PDF PubMed Google Scholar). Although several PLA2s have been and well characterized (3.Shimizu T. Ohto T. Kita Y. IUBMB Life. 2006; 58: 328-333Crossref PubMed Scopus (69) Google the cloning and characterization of acyltransferases are only LPLATs were recently to be remodeling and their are in LCLAT1 and is the only known glycerophospholipid and of four fatty acyl a CL is for the activity of several key mitochondrial enzymes involved in M. Rua D. Greenberg M.L. Prog. Lipid Res. 2000; 39: 257-288Crossref PubMed Scopus (651) Google Scholar). CL is synthesized from and by LCLAT1 (called by Cao was and to LPLAT motifs J. Y. J. P. Y. J. Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). of LCLAT1 in cells or cells to a in and The and as a preference for 18:1- and LCLAT1 is the in the and LCLAT1 was in the localized to the ER. The was by the of a an signal at the S. Li M. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar) of Although AGPAT8 was reported as an LCLAT, were not in A. Arch. Biochem. Biophys. 2006; PubMed Scopus Google Scholar). CL remodeling is to play an important role in the of functions. CL is a family by of that as and M. A. T. R.J. S. J. PubMed Scopus Google Scholar). Thus, studies of are to the role of CL remodeling in is a for the of CL and a of the family, including A.P. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The cloned LCLAT1 that the of from lyso-PG and Y. Cao J. Y. J. Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). The also possesses the LPLAT in cells a preference for and as donors, which is the composition of in several tissues. is distributed in tissues. The has the and is localized to the Y. Cao J. Y. J. Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). These two studies are a in studies on acyltransferases at the and H. H. D. T. R. A. R. Shimizu T. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar) and M.L. R.J. Proc. Natl. Acad. Sci. U. S. A. 2006; 103: PubMed Scopus Google Scholar) independently discovered (also called or which has LPLAT motifs and synthesis. The is expressed mainly in the in and mRNA is during the is a of which and is to be an important in the of and R.A. 2007; Full Text Full Text PDF PubMed Scopus Google Scholar). Thus, may the PC of and play a role in is of that or and the lipid composition of studies are to the roles of in and to is a between and lipid synthesis. (called and was by as the involved in PAF biosynthesis in the remodeling pathway H. D. Nakanishi H. T. S. R. Shimizu T. J. Biol. Chem. 2007; Full Text Full Text PDF PubMed Scopus Google Scholar). also has the LPLAT, and which is to the ER. The level of was in and by and Moreover, in mouse the mRNA level of was by and of which are cell The was by Because the not is by but not by also possesses activity as the The is which is a membrane of cells as well as a of is from by PLA2s and used to form PAF (Fig. (3.Shimizu T. Ohto T. Kita Y. IUBMB Life. 2006; 58: 328-333Crossref PubMed Scopus (69) Google Scholar, H. S. N. Shimizu T. Biochem. Biophys. Res. 2000; PubMed Scopus Google Scholar). Thus, is a important not only in the biosynthesis of PAF but also in membrane of cells the activated and is that is and activated by because an of this the of and H. D. Nakanishi H. T. S. R. Shimizu T. J. Biol. Chem. 2007; Full Text Full Text PDF PubMed Scopus Google Scholar, H. S. M. K. S. Shimizu T. J. PubMed Scopus Google Scholar). specific of may be than PAF because they also of cells by membrane will be important to and of including of for substrate and will be to the regulation of recent that not only but also PAF (Fig. T. H. R. A. Shimizu T. J. Biol. Chem. 2008; 283: Full Text Full Text PDF PubMed Scopus Google Scholar). In mouse was activated by which was in to Moreover, and have only of that the LPLAT is an in Thus, two distinct are a expressed and an This is to and which are expressed and R. J. PubMed Scopus Google Scholar). This that are two of PAF remodeling the and remodeling pathways T. H. R. A. Shimizu T. J. Biol. Chem. 2008; 283: Full Text Full Text PDF PubMed Scopus Google Scholar). Recently, an that is to and was characterized and renamed as (also called and J. D. T. Li D. L. Tobin J.F. Gimeno R.E. J. Biol. Chem. 2008; 283: Full Text Full Text PDF PubMed Scopus Google Scholar). possesses LPEAT, LPGAT, LPSAT, and 18:1- or only activity in cells. Because the is expressed mainly in the was that is an important for the of PE. In has been reported that has activity in activity is H. Proc. Natl. Acad. Sci. U. S. A. 2008; PubMed Scopus Google Scholar). family members are acyltransferases K. Biochem. Sci. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, T. Rev. Google Scholar). a of these enzymes is of the and and acyltransferases and are members of the family. the family also such as and R. Y. T. N. S. H. T. S. Cell. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar, Li T. 2004; PubMed Scopus Google Scholar, R. M. A. Mol. Biol. Cell. 2006; PubMed Scopus Google Scholar). is for of at for R. Y. T. N. S. H. T. S. Cell. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar). a in and this is for activity as well as for the of a in the Li T. 2004; PubMed Scopus Google Scholar). In the is to catalyze the remodeling of the R. M. A. Mol. Biol. Cell. 2006; PubMed Scopus Google Scholar). members of the family have not been characterized, such as and In the of groups independently reported an in that several LPLAT J. J.L. Voelker D.R. J. Biol. Chem. 2007; Full Text Full Text PDF PubMed Scopus Google Scholar, M. C. J. A. J. Biol. Chem. 2007; Full Text Full Text PDF PubMed Scopus Google Scholar, S. N. N. M. C. P. J. Biol. Chem. 2007; Full Text Full Text PDF PubMed Scopus Google Scholar, H. A. Y. M. J. M. H. H. R. H. J. Biol. 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Thus, these that the family is a LPLAT family. mRNA was the in the On the other hand, mouse mRNA was highly expressed in the and and mouse mRNA was highly expressed in the and higher polyunsaturated fatty acyl-CoAs and 18:2-CoA than saturated fatty whereas and a preference for (Table 1). and higher activity than or as an were between and of on the and higher activity than and higher activity than for lyso-PE and Using as a LPCAT, LPEAT, and were to be in cells Thus, to be a key LPCAT, LPEAT, and in cells D. H. S. Nakanishi H. R. Shimizu T. Proc. Natl. Acad. Sci. U. S. A. 2008; PubMed Scopus Google Scholar). and were localized to the enzymes were in which is the in the of the formation of that the membrane components were in cells D. H. S. Nakanishi H. R. Shimizu T. Proc. Natl. Acad. Sci. U. S. A. 2008; PubMed Scopus Google Scholar). The and of these to be (also called and was as the first LPIAT, which the of arachidonic acid and eicosapentaenoic acid into lyso-PI T. R. N. S. S. K. S. H. Mol. Biol. Cell. 2008; PubMed Scopus Google Scholar). of that a a is important for of a of the the a that multiple Recently, was as a which of an an J. M.S. G. J.L. Cell. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar). is important for the activity of Thus, the family is composed of enzymes that fatty acids into acid and is which acid or motifs are important in between and proteins as In the many LPLATs have been identified, in the most in the LPLAT the of the Kennedy pathway and the Lands' 50 In this review, we propose to LPLATs to and the nomenclature (Table 1). The that additional LPLATs, for contribute to membrane composition and diversity will be in The of multiple LPLATs is of the distinct and acyltransferases that acids into M. D. Rev. Biochem. 2000; PubMed Scopus Google Scholar). The and substrate of LPLATs may the diversity in membrane glycerophospholipids, which tissues and in to a of has been in to the of studies will be to the roles of these enzymes in will also be important to substrates of acyl-CoAs and to the functional of and recent findings LPLATs a the by Dr. Lands to (8.Lands W.E. Biochim. Biophys. Acta. 2000; 1483: 1-14Crossref PubMed Scopus (120) Google Scholar) and may will the to of the of membrane diversity and