Abstract
Phospholipids are present in all living organisms. They are a major component of all biological membranes, along with glycolipids and cholesterol. Enzymes aimed at cleaving the various bonds in phospholipids, namely phospholipases, are consequently widespread in nature, playing very diverse roles from aggression in snake venom to signal transduction, lipid mediators production, and digestion in humans. Although all phospholipases target phospholipids as substrates, they vary in the site of action on the phospholipids molecules, physiological function, mode of action, and their regulation. Significant studies on phospholipases characterization, physiological role, and industrial potential have been conducted worldwide. Some of them have been directed for biotechnological advances, such as gene discovery and functional enhancement by protein engineering. Others reported phospholipases as virulence factors and major causes of pathophysiological effects. In this introductory chapter, we provide brief details of different phospholipases.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Exton JH (1997) New developments in phospholipase D. J Biol Chem 272:15579–15582
Farn JL, Strugnell RA, Hoyne PA et al (2001) Molecular characterization of a secreted enzyme with phospholipase B activity from Moraxella bovis. J Bacteriol 183:6717–6720
Singer WD, Brown HA, Sternweis PC (1997) Regulation of eukaryotic phosphatidylinositol-specific phospholipase C and phospholipase D. Annu Rev Biochem 66:475–509
Bornscheuer UT, Kazlauskas RJ (2004) Catalytic promiscuity in biocatalysis: using old enzymes to form new bonds and follow new pathways. Angew Chem Int Ed Engl 43:6032–6040
De Maria L, Vind J, Oxenboll KM et al (2007) Phospholipases and their industrial applications. Appl Microbiol Biotechnol 74:290–300
Kazlauskas RJ (2005) Enhancing catalytic promiscuity for biocatalysis. Curr Opin Chem Biol 9:195–201
Aoki J, Nagai Y, Hosono H et al (2002) Structure and function of phosphatidylserine-specific phospholipase A1. Biochim Biophys Acta 1582:26–32
Sato T, Aoki J, Nagai Y et al (1997) Serine phospholipid-specific phospholipase A that is secreted from activated platelets. A new member of the lipase family. J Biol Chem 272:2192–2198
King TP, Kochoumian L, Joslyn A (1984) Wasp venom proteins: phospholipase A1 and B. Arch Biochem Biophys 230:1–12
Hiramatsu T, Sonoda H, Takanezawa Y et al (2003) Biochemical and molecular characterization of two phosphatidic acid-selective phospholipase A1s, mPA-PLA1alpha and mPA-PLA1beta. J Biol Chem 278:49438–49447
Carriere F, Withers-Martinez C, van Tilbeurgh H et al (1998) Structural basis for the substrate selectivity of pancreatic lipases and some related proteins. Biochim Biophys Acta 1376:417–432
Simons JW, Gotz F, Egmond MR et al (1998) Biochemical properties of staphylococcal (phospho)lipases. Chem Phys Lipids 93:27–37
Tiesinga JJ, van Pouderoyen G, Nardini M et al (2007) Structural basis of phospholipase activity of Staphylococcus hyicus lipase. J Mol Biol 371:447–456
Heikinheimo P, Goldman A, Jeffries C et al (1999) Of barn owls and bankers: a lush variety of alpha/beta hydrolases. Structure 7:R141–R146
Simons JW, Boots JW, Kats MP et al (1997) Dissecting the catalytic mechanism of staphylococcal lipases using carbamate substrates: chain length selectivity, interfacial activation, and cofactor dependence. Biochemistry 36:14539–14550
Dekker N (2000) Outer-membrane phospholipase A: known structure, unknown biological function. Mol Microbiol 35:711–717
Kingma RL, Fragiathaki M, Snijder HJ et al (2000) Unusual catalytic triad of Escherichia coli outer membrane phospholipase A. Biochemistry 39:10017–10022
Snijder HJ, Dijkstra BW (2000) Bacterial phospholipase A: structure and function of an integral membrane phospholipase. Biochim Biophys Acta 1488:91–101
Schmiel DH, Wagar E, Karamanou L et al (1998) Phospholipase A of Yersinia enterocolitica contributes to pathogenesis in a mouse model. Infect Immun 66:3941–3951
Murakami M, Taketomi Y, Miki Y et al (2011) Recent progress in phospholipase A(2) research: From cells to animals to humans. Prog Lipid Res 50:152–192
Schaloske RH, Dennis EA (2006) The phospholipase A2 superfamily and its group numbering system. Biochim Biophys Acta 1761:1246–1259
Valentin E, Singer AG, Ghomashchi F et al (2000) Cloning and recombinant expression of human group IIF-secreted phospholipase A(2). Biochem Biophys Res Commun 279:223–228
Lee HY, Bahn SC, Shin JS et al (2005) Multiple forms of secretory phospholipase A2 in plants. Prog Lipid Res 44:52–67
Ryu Y, Oh Y, Yoon J et al (2003) Molecular characterization of a gene encoding the Drosophila melanogaster phospholipase A2. Biochim Biophys Acta 1628:206–210
McIntosh JM, Ghomashchi F, Gelb MH et al (1995) Conodipine-M, a novel phospholipase A2 isolated from the venom of the marine snail Conus magus. J Biol Chem 270:3518–3526
Kini RM (2003) Excitement ahead: structure, function and mechanism of snake venom phospholipase A2 enzymes. Toxicon 42:827–840
Valentin E, Lambeau G (2000) Increasing molecular diversity of secreted phospholipases A(2) and their receptors and binding proteins. Biochim Biophys Acta 1488:59–70
Canaan S, Zadori Z, Ghomashchi F et al (2004) Interfacial enzymology of parvovirus phospholipases A2. J Biol Chem 279:14502–14508
Soragni E, Bolchi A, Balestrini R et al (2001) A nutrient-regulated, dual localization phospholipase A(2) in the symbiotic fungus Tuber borchii. EMBO J 20:5079–5090
Sugiyama M, Ohtani K, Izuhara M et al (2002) A novel prokaryotic phospholipase A2. Characterization, gene cloning, and solution structure. J Biol Chem 277:20051–20058
Matoba Y, Katsube Y, Sugiyama M (2002) The crystal structure of prokaryotic phospholipase A2. J Biol Chem 277:20059–20069
Valentin E, Ghomashchi F, Gelb MH et al (2000) Novel human secreted phospholi-pase A(2) with homology to the group III bee venom enzyme. J Biol Chem 275:7492–7496
Singer AG, Ghomashchi F, Le Calvez C et al (2002) Interfacial kinetic and binding properties of the complete set of human and mouse groups I, II, V, X, and XII secreted phospholipases A2. J Biol Chem 277:48535–48549
Ni Z, Okeley NM, Smart BP et al (2006) Intracellular actions of group IIA secreted phospholipase A2 and group IVA cytosolic phospholipase A2 contribute to arachidonic acid release and prostaglandin production in rat gastric mucosal cells and transfected human embryonic kidney cells. J Biol Chem 281:16245–16255
Mounier CM, Ghomashchi F, Lindsay MR et al (2004) Arachidonic acid release from mammalian cells transfected with human groups IIA and X secreted phospholipase A(2) occurs predominantly during the secretory process and with the involvement of cytosolic phospholipase A(2)-alpha. J Biol Chem 279:25024–25038
Bezzine S, Koduri RS, Valentin E et al (2000) Exogenously added human group X secreted phospholipase A(2) but not the group IB, IIA, and V enzymes efficiently release arachidonic acid from adherent mammalian cells. J Biol Chem 275:3179–3191
Koduri RS, Gronroos JO, Laine VJ et al (2002) Bactericidal properties of human and murine groups I, II, V, X, and XII secreted phospholipases A(2). J Biol Chem 277:5849–5857
Webb NR (2005) Secretory phospholipase A2 enzymes in atherogenesis. Curr Opin Lipidol 16:341–344
Kudo I, Murakami M, Hara S et al (1993) Mammalian non-pancreatic phospholipases A2. Biochim Biophys Acta 1170:217–231
Akiba S, Hatazawa R, Ono K et al (2001) Secretory phospholipase A2 mediates cooperative prostaglandin generation by growth factor and cytokine independently of preceding cytosolic phospholipase A2 expression in rat gastric epithelial cells. J Biol Chem 276:21854–21862
Kim KP, Rafter JD, Bittova L et al (2001) Mechanism of human group V phospholipase A2 (PLA2)-induced leukotriene biosynthesis in human neutrophils. A potential role of heparan sulfate binding in PLA2 internalization and degradation. J Biol Chem 276:11126–11134
Snitko Y, Yoon ET, Cho W (1997) High specificity of human secretory class II phospholipase A2 for phosphatidic acid. Biochem J 321:737–741
Fourcade O, Simon MF, Viode C et al (1995) Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells. Cell 80:919–927
Atsumi G, Murakami M, Tajima M et al (1997) The perturbed membrane of cells undergoing apoptosis is susceptible to type II secretory phospholipase A2 to liberate arachidonic acid. Biochim Biophys Acta 1349:43–54
Nevalainen TJ, Graham GG, Scott KF (2008) Antibacterial actions of secreted phospholipases A2. Review. Biochim Biophys Acta 1781:1–9
Koprivnjak T, Peschel A, Gelb MH et al (2002) Role of charge properties of bacterial envelope in bactericidal action of human group IIA phospholipase A2 against Staphylococcus aureus. J Biol Chem 277:47636–47644
Chen J, Shao C, Lazar V et al (1997) Localization of group IIc low molecular weight phospholipase A2 mRNA to meiotic cells in the mouse. J Cell Biochem 64:369–375
Tischfield JA, Xia YR, Shih DM et al (1996) Low-molecular-weight, calcium-dependent phospholipase A2 genes are linked and map to homologous chromosome regions in mouse and human. Genomics 32:328–333
Valentin E, Koduri RS, Scimeca JC et al (1999) Cloning and recombinant expression of a novel mouse-secreted phospholipase A2. J Biol Chem 274:19152–19160
Ishizaki J, Suzuki N, Higashino K et al (1999) Cloning and characterization of novel mouse and human secretory phospholipase A(2)s. J Biol Chem 274:24973–24979
Chen J, Engle SJ, Seilhamer JJ et al (1994) Cloning and recombinant expression of a novel human low molecular weight Ca(2+)-dependent phospholipase A2. J Biol Chem 269:2365–2368
Murakami M, Koduri RS, Enomoto A et al (2001) Distinct arachidonate-releasing functions of mammalian secreted phospholipase A2s in human embryonic kidney 293 and rat mastocytoma RBL-2H3 cells through heparan sulfate shuttling and external plasma membrane mechanisms. J Biol Chem 276:10083–10096
Kim YM, Lee YM, Kim HS et al (2002) TNF-related activation-induced cytokine (TRANCE) induces angiogenesis through the activation of Src and phospholipase C (PLC) in human endothelial cells. J Biol Chem 277:6799–6805
Balboa MA, Shirai Y, Gaietta G et al (2003) Localization of group V phospholipase A2 in caveolin-enriched granules in activated P388D1 macrophage-like cells. J Biol Chem 278:48059–48065
Wijewickrama GT, Kim JH, Kim YJ et al (2006) Systematic evaluation of transcellular activities of secretory phospholipases A2. High activity of group V phospholipases A2 to induce eicosanoid biosynthesis in neighboring inflammatory cells. J Biol Chem 281:10935–10944
Munoz NM, Meliton AY, Lambertino A et al (2006) Transcellular secretion of group V phospholipase A2 from epithelium induces beta 2-integrin-mediated adhesion and synthesis of leukotriene C4 in eosinophils. J Immunol 177:574–582
Ohtsuki M, Taketomi Y, Arata S et al (2006) Transgenic expression of group V, but not group X, secreted phospholipase A2 in mice leads to neonatal lethality because of lung dysfunction. J Biol Chem 281:36420–36433
Wooton-Kee CR, Boyanovsky BB, Nasser MS et al (2004) Group V sPLA2 hydrolysis of low-density lipoprotein results in spontaneous particle aggregation and promotes macrophage foam cell formation. Arterioscler Thromb Vasc Biol 24:762–767
Ishimoto Y, Yamada K, Yamamoto S et al (2003) Group V and X secretory phospholipase A(2)s-induced modification of high-density lipoprotein linked to the reduction of its antiatherogenic functions. Biochim Biophys Acta 1642:129–138
Gesquiere L, Cho W, Subbaiah PV (2002) Role of group IIa and group V secretory phospholipases A(2) in the metabolism of lipoproteins. Substrate specificities of the enzymes and the regulation of their activities by sphingomyelin. Biochemistry 41:4911–4920
Mitsuishi M, Masuda S, Kudo I et al (2007) Human group III phospholipase A2 suppresses adenovirus infection into host cells. Evidence that group III, V and X phospholipase A2s act on distinct cellular phospholipid molecular species. Biochim Biophys Acta 1771:1389–1396
Boilard E, Lai Y, Larabee K et al (2010) A novel anti-inflammatory role for secretory phospholipase A2 in immune complex-mediated arthritis. EMBO Mol Med 2:172–187
Balestrieri B, Hsu VW, Gilbert H et al (2006) Group V secretory phospholipase A2 translocates to the phagosome after zymosan stimulation of mouse peritoneal macrophages and regulates phagocytosis. J Biol Chem 281:6691–6698
Bradley JD, Dmitrienko AA, Kivitz AJ et al (2005) A randomized, double-blinded, placebo-controlled clinical trial of LY333013, a selective inhibitor of group II secretory phospholipase A2, in the treatment of rheumatoid arthritis. J Rheumatol 32:417–423
Rosengren B, Peilot H, Umaerus M et al (2006) Secretory phospholipase A2 group V: lesion distribution, activation by arterial proteoglycans, and induction in aorta by a Western diet. Arterioscler Thromb Vasc Biol 26:1579–1585
Boyanovsky BB, van der Westhuyzen DR, Webb NR (2005) Group V secretory phospholipase A2-modified low density lipoprotein promotes foam cell formation by a SR-A- and CD36-independent process that involves cellular proteoglycans. J Biol Chem 280:32746–32752
Bostrom MA, Boyanovsky BB, Jordan CT et al (2007) Group v secretory phospholipase A2 promotes atherosclerosis: evidence from genetically altered mice. Arterioscler Thromb Vasc Biol 27:600–606
Masuda S, Murakami M, Mitsuishi M et al (2005) Expression of secretory phospholipase A2 enzymes in lungs of humans with pneumonia and their potential prostaglandin-synthetic function in human lung-derived cells. Biochem J 387:27–38
Masuda S, Murakami M, Ishikawa Y et al (2005) Diverse cellular localizations of secretory phospholipase A2 enzymes in several human tissues. Biochim Biophys Acta 1736:200–210
Balestrieri B, Maekawa A, Xing W et al (2009) Group V secretory phospholipase A2 modulates phagosome maturation and regulates the innate immune response against Candida albicans. J Immunol 182:4891–4898
Morioka Y, Saiga A, Yokota Y et al (2000) Mouse group X secretory phospholipase A2 induces a potent release of arachidonic acid from spleen cells and acts as a ligand for the phospholipase A2 receptor. Arch Biochem Biophys 381:31–42
Mounier CM, Wendum D, Greenspan E et al (2008) Distinct expression pattern of the full set of secreted phospholipases A2 in human colorectal adenocarcinomas: sPLA2-III as a biomarker candidate. Br J Cancer 98:587–595
Eerola LI, Surrel F, Nevalainen TJ et al (2006) Analysis of expression of secreted phospholipases A2 in mouse tissues at protein and mRNA levels. Biochim Biophys Acta 1761:745–756
Surrel F, Jemel I, Boilard E et al (2009) Group X phospholipase A2 stimulates the proliferation of colon cancer cells by producing various lipid mediators. Mol Pharmacol 76:778–790
Hite RD, Seeds MC, Jacinto RB et al (1998) Hydrolysis of surfactant-associated phosphatidylcholine by mammalian secretory phospholipases A2. Am J Physiol 275:L740–L747
Pruzanski W, Lambeau L, Lazdunsky M et al (2005) Differential hydrolysis of molecular species of lipoprotein phosphatidylcholine by groups IIA, V and X secretory phospholipases A2. Biochim Biophys Acta 1736:38–50
Karabina SA, Brocheriou I, Le Naour G et al (2006) Atherogenic properties of LDL particles modified by human group X secreted phospholipase A2 on human endothelial cell function. FASEB J 20:2547–2549
Hallstrand TS, Chi EY, Singer AG et al (2007) Secreted phospholipase A2 group X overexpression in asthma and bronchial hyperresponsiveness. Am J Respir Crit Care Med 176:1072–1078
Henderson WR Jr, Chi EY, Bollinger JG et al (2007) Importance of group X-secreted phospholipase A2 in allergen-induced airway inflammation and remodeling in a mouse asthma model. J Exp Med 204:865–877
Giannattasio G, Fujioka D, Xing W et al (2010) Group V secretory phospholipase A2 reveals its role in house dust mite-induced allergic pulmonary inflammation by regulation of dendritic cell function. J Immunol 185:4430–4438
Munoz NM, Meliton AY, Meliton LN et al (2009) Secretory group V phospholipase A2 regulates acute lung injury and neutrophilic inflammation caused by LPS in mice. Am J Physiol Lung Cell Mol Physiol 296:L879–L887
Sato H, Kato R, Isogai Y et al (2008) Analyses of group III secreted phospholipase A2 transgenic mice reveal potential participation of this enzyme in plasma lipoprotein modification, macrophage foam cell formation, and atherosclerosis. J Biol Chem 283:33483–33497
Kimura-Matsumoto M, Ishikawa Y, Komiyama K et al (2008) Expression of secretory phospholipase A2s in human atherosclerosis development. Atherosclerosis 196:81–91
Masuda S, Murakami M, Matsumoto S et al (2004) Localization of various secretory phospholipase A2 enzymes in male reproductive organs. Biochim Biophys Acta 1686:61–76
Escoffier J, Jemel I, Tanemoto A et al (2010) Group X phospholipase A2 is released during sperm acrosome reaction and controls fertility outcome in mice. J Clin Invest 120:1415–1428
Gelb MH, Valentin E, Ghomashchi F et al (2000) Cloning and recombinant expression of a structurally novel human secreted phospholipase A2. J Biol Chem 275:39823–39826
Huhtinen HT, Gronroos JO, Gronroos JM et al (2006) Antibacterial effects of human group IIA and group XIIA phospholipase A2 against Helicobacter pylori in vitro. APMIS 114:127–130
Rouault M, Bollinger JG, Lazdunski M et al (2003) Novel mammalian group XII secreted phospholipase A2 lacking enzymatic activity. Biochemistry 42:11494–11503
Chabot S, Koumanov K, Lambeau G et al (2003) Inhibitory effects of surfactant protein A on surfactant phospholipid hydrolysis by secreted phospholipases A2. J Immunol 171:995–1000
Saegusa J, Akakura N, Wu CY et al (2008) Pro-inflammatory secretory phospholipase A2 type IIA binds to integrins alphavbeta3 and alpha4beta1 and induces proliferation of monocytic cells in an integrin-dependent manner. J Biol Chem 283:26107–26115
Cintra-Francischinelli M, Pizzo P, Angulo Y et al (2010) The C-terminal region of a Lys49 myotoxin mediates Ca2+ influx in C2C12 myotubes. Toxicon 55:590–596
Boilard E, Bourgoin SG, Bernatchez C et al (2003) Identification of an autoantigen on the surface of apoptotic human T cells as a new protein interacting with inflammatory group IIA phospholipase A2. Blood 102:2901–2909
Smart BP, Oslund RC, Walsh LA et al (2006) The first potent inhibitor of mammalian group X secreted phospholipase A2: elucidation of sites for enhanced binding. J Med Chem 49:2858–2860
Sato R, Yamaga S, Watanabe K et al (2010) Inhibition of secretory phospholipase A2 activity attenuates lipopolysaccharide-induced acute lung injury in a mouse model. Exp Lung Res 36:191–200
Fujioka D, Saito Y, Kobayashi T et al (2008) Reduction in myocardial ischemia/reperfusion injury in group X secretory phospholipase A2-deficient mice. Circulation 117:2977–2985
Bowton DL, Dmitrienko AA, Israel E et al (2005) Impact of a soluble phospholipase A2 inhibitor on inhaled allergen challenge in subjects with asthma. J Asthma 42:65–71
Zeiher BG, Steingrub J, Laterre PF et al (2005) LY315920NA/S–5920, a selective inhibitor of group IIA secretory phospholipase A2, fails to improve clinical outcome for patients with severe sepsis. Crit Care Med 33:1741–1748
Ghosh M, Tucker DE, Burchett SA et al (2006) Properties of the Group IV phospholipase A2 family. Prog Lipid Res 45:487–510
Leslie CC (2004) Regulation of arachidonic acid availability for eicosanoid production. Biochem Cell Biol 82:1–17
Leslie CC (2004) Regulation of the specific release of arachidonic acid by cytosolic phospholipase A2. Prostaglandins Leukot Essent Fatty Acids 70:373–376
Jimenez JL, Smith GR, Contreras-Moreira B et al (2003) Functional recycling of C2 domains throughout evolution: a comparative study of synaptotagmin, protein kinase C and phospholipase C by sequence, structural and modelling approaches. J Mol Biol 333:621–639
Hirabayashi T, Murayama T, Shimizu T (2004) Regulatory mechanism and physiological role of cytosolic phospholipase A2. Biol Pharm Bull 27:1168–1173
Pickard RT, Chiou XG, Strifler BA et al (1996) Identification of essential residues for the catalytic function of 85-kDa cytosolic phospholipase A2. Probing the role of histidine, aspartic acid, cysteine, and arginine. J Biol Chem 271:19225–19231
Dessen A (2000) Structure and mechanism of human cytosolic phospholipase A(2). Biochim Biophys Acta 1488:40–47
Ohto T, Uozumi N, Hirabayashi T et al (2005) Identification of novel cytosolic phospholipase A(2)s, murine cPLA(2){delta}, {epsilon}, and {zeta}, which form a gene cluster with cPLA(2){beta}. J Biol Chem 280:24576–24583
Ghosh M, Loper R, Ghomashchi F et al (2007) Function, activity, and membrane targeting of cytosolic phospholipase A(2)zeta in mouse lung fibroblasts. J Biol Chem 282:11676–11686
Ghomashchi F, Naika GS, Bollinger JG et al (2010) Interfacial kinetic and binding properties of mammalian group IVB phospholipase A2 (cPLA2beta) and comparison with the other cPLA2 isoforms. J Biol Chem 285:36100–36111
Haq S, Kilter H, Michael A et al (2003) Deletion of cytosolic phospholipase A2 promotes striated muscle growth. Nat Med 9:944–951
Nagase T, Uozumi N, Ishii S et al (2002) A pivotal role of cytosolic phospholipase A(2) in bleomycin-induced pulmonary fibrosis. Nat Med 8:480–484
Miyaura C, Inada M, Matsumoto C et al (2003) An essential role of cytosolic phospholipase A2alpha in prostaglandin E2-mediated bone resorption associated with inflammation. J Exp Med 197:1303–1310
Hegen M, Sun L, Uozumi N et al (2003) Cytosolic phospholipase A2alpha-deficient mice are resistant to collagen-induced arthritis. J Exp Med 197:1297–1302
Bonventre J (2004) Cytosolic phospholipase A2alpha reigns supreme in arthritis and bone resorption. Trends Immunol 25:116–119
Sanchez-Mejia RO, Newman JW, Toh S et al (2008) Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer’s disease. Nat Neurosci 11:1311–1318
Hartney JM, Coggins KG, Tilley SL et al (2006) Prostaglandin E2 protects lower airways against bronchoconstriction. Am J Physiol Lung Cell Mol Physiol 290:L105–L113
Francois H, Athirakul K, Howell D et al (2005) Prostacyclin protects against elevated blood pressure and cardiac fibrosis. Cell Metab 2:201–207
Ilsley JN, Nakanishi M, Flynn C et al (2005) Cytoplasmic phospholipase A2 deletion enhances colon tumorigenesis. Cancer Res 65:2636–2643
Meyer AM, Dwyer-Nield LD, Hurteau GJ et al (2004) Decreased lung tumorigenesis in mice genetically deficient in cytosolic phospholipase A2. Carcinogenesis 25:1517–1524
Downey P, Sapirstein A, O’Leary E et al (2001) Renal concentrating defect in mice lacking group IV cytosolic phospholipase A(2). Am J Physiol Renal Physiol 280:F607–F618
Wong DA, Kita Y, Uozumi N et al (2002) Discrete role for cytosolic phospholipase A(2)alpha in platelets: studies using single and double mutant mice of cytosolic and group IIA secretory phospholipase A(2). J Exp Med 196:349–357
Adler DH, Cogan JD, Phillips JA 3rd et al (2008) Inherited human cPLA(2alpha) deficiency is associated with impaired eicosanoid biosynthesis, small intestinal ulceration, and platelet dysfunction. J Clin Invest 118:2121–2131
Reed KA, Tucker DE, Aloulou A et al (2011) Functional Characterization of Mutations in Inherited Human cPLA(2) Deficiency. Biochemistry 50:1731–1738
Akiba S, Sato T (2004) Cellular function of calcium-independent phospholipase A2. Biol Pharm Bull 27:1174–1178
Balsinde J, Balboa MA (2005) Cellular regulation and proposed biological functions of group VIA calcium-independent phospholipase A2 in activated cells. Cell Signal 17:1052–1062
Lio YC, Dennis EA (1998) Interfacial activation, lysophospholipase and transacylase activity of group VI Ca2+-independent phospholipase A2. Biochim Biophys Acta 1392:320–332
Jenkins CM, Yan W, Mancuso DJ et al (2006) Highly selective hydrolysis of fatty acyl-CoAs by calcium-independent phospholipase A2beta. Enzyme autoacylation and acyl-CoA-mediated reversal of calmodulin inhibition of phospholipase A2 activity. J Biol Chem 281:15615–15624
Sharma J, Turk J, McHowat J (2010) Endothelial cell prostaglandin I(2) and platelet-activating factor production are markedly attenuated in the calcium-independent phospholipase A(2)beta knockout mouse. Biochemistry 49:5473–5481
Yan W, Jenkins CM, Han X et al (2005) The highly selective production of 2-arachidonoyl lysophosphatidylcholine catalyzed by purified calcium-independent phospholipase A2gamma: identification of a novel enzymatic mediator for the generation of a key branch point intermediate in eicosanoid signaling. J Biol Chem 280:26669–26679
Jenkins CM, Mancuso DJ, Yan W et al (2004) Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. J Biol Chem 279:48968–48975
Ghosh M, Loper R, Gelb MH et al (2006) Identification of the expressed form of human cytosolic phospholipase A2beta (cPLA2beta): cPLA2beta3 is a novel variant localized to mitochondria and early endosomes. J Biol Chem 281:16615–16624
Wilensky RL, Macphee CH (2009) Lipoprotein-associated phospholipase A(2) and atherosclerosis. Curr Opin Lipidol 20:415–420
Packard CJ (2009) Lipoprotein-associated phospholipase A2 as a biomarker of coronary heart disease and a therapeutic target. Curr Opin Cardiol 24:358–363
Arai H (2002) Platelet-activating factor acetylhydrolase. Prostaglandins Other Lipid Mediat 68–69:83–94
Tjoelker LW, Wilder C, Eberhardt C et al (1995) Anti-inflammatory properties of a platelet-activating factor acetylhydrolase. Nature 374:549–553
Samanta U, Bahnson BJ (2008) Crystal structure of human plasma platelet-activating factor acetylhydrolase: structural implication to lipoprotein binding and catalysis. J Biol Chem 283:31617–31624
Stafforini DM, Tjoelker LW, McCormick SP et al (1999) Molecular basis of the interaction between plasma platelet-activating factor acetylhydrolase and low density lipoprotein. J Biol Chem 274:7018–7024
Prescott SM, Zimmerman GA, Stafforini DM et al (2000) Platelet-activating factor and related lipid mediators. Annu Rev Biochem 69:419–445
Tsimikas S, Tsironis LD, Tselepis AD (2007) New insights into the role of lipoprotein(a)-associated lipoprotein-associated phospholipase A2 in atherosclerosis and cardiovascular disease. Arterioscler Thromb Vasc Biol 27:2094–2099
Macphee CH, Nelson JJ, Zalewski A (2005) Lipoprotein-associated phospholipase A2 as a target of therapy. Curr Opin Lipidol 16:442–446
Wilensky RL, Shi Y, Mohler ER 3rd et al (2008) Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development. Nat Med 14:1059–1066
Serruys PW, Garcia-Garcia HM, Buszman P et al (2008) Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque. Circulation 118:1172–1182
Kono N, Inoue T, Yoshida Y et al (2008) Protection against oxidative stress-induced hepatic injury by intracellular type II platelet-activating factor acetylhydrolase by metabolism of oxidized phospholipids in vivo. J Biol Chem 283:1628–1636
Manya H, Aoki J, Watanabe M et al (1998) Switching of platelet-activating factor acetylhydrolase catalytic subunits in developing rat brain. J Biol Chem 273:18567–18572
Kitsiouli E, Nakos G, Lekka ME (2009) Phospholipase A2 subclasses in acute respiratory distress syndrome. Biochim Biophys Acta 1792:941–953
Kim TS, Sundaresh CS, Feinstein SI et al (1997) Identification of a human cDNA clone for lysosomal type Ca2+-independent phospholipase A2 and properties of the expressed protein. J Biol Chem 272:2542–2550
Chen JW, Dodia C, Feinstein SI et al (2000) 1-Cys peroxiredoxin, a bifunctional enzyme with glutathione peroxidase and phospholipase A2 activities. J Biol Chem 275:28421–28427
Bridges JP, Ikegami M, Brilli LL et al (2010) LPCAT1 regulates surfactant phospholipid synthesis and is required for transitioning to air breathing in mice. J Clin Invest 120:1736–1748
Hiraoka M, Abe A, Lu Y et al (2006) Lysosomal phospholipase A2 and phospholipidosis. Mol Cell Biol 26:6139–6148
Duncan RE, Sarkadi-Nagy E, Jaworski K et al (2008) Identification and functional characterization of adipose-specific phospholipase A2 (AdPLA). J Biol Chem 283:25428–25436
Sers C, Emmenegger U, Husmann K et al (1997) Growth-inhibitory activity and downregulation of the class II tumor-suppressor gene H-rev107 in tumor cell lines and experimental tumors. J Cell Biol 136:935–944
Uyama T, Morishita J, Jin XH et al (2009) The tumor suppressor gene H-Rev107 functions as a novel Ca2+-independent cytosolic phospholipase A1/2 of the thiol hydrolase type. J Lipid Res 50:685–693
Sanchez-Alavez M, Klein I, Brownell SE et al (2007) Night eating and obesity in the EP3R-deficient mouse. Proc Natl Acad Sci USA 104:3009–3014
Morgan CP, Insall R, Haynes L et al (2004) Identification of phospholipase B from Dictyostelium discoideum reveals a new lipase family present in mammals, flies and nematodes, but not yeast. Biochem J 382:441–449
Chen SC, Wright LC, Santangelo RT et al (1997) Identification of extracellular phospholipase B, lysophospholipase, and acyltransferase produced by Cryptococcus neoformans. Infect Immun 65:405–411
Lu T, Ito M, Tchoua U et al (2001) Identification of essential residues for catalysis of rat intestinal phospholipase B/lipase. Biochemistry 40:7133–7139
Ghannoum MA (1998) Extracellular phospholipases as universal virulence factor in pathogenic fungi. Nippon Ishinkin Gakkai Zasshi 39:55–59
Schwarzer N, Nost R, Seybold J et al (1998) Two distinct phospholipases C of Listeria monocytogenes induce ceramide generation, nuclear factor-kappa B activation, and E-selectin expression in human endothelial cells. J Immunol 161:3010–3018
Katan M (1998) Families of phosphoinositide-specific phospholipase C: structure and function. Biochim Biophys Acta 1436:5–17
Heinz DW, Essen LO, Williams RL (1998) Structural and mechanistic comparison of prokaryotic and eukaryotic phosphoinositide-specific phospholipases C. J Mol Biol 275:635–650
Iwasaki Y, Nishikawa S, Tsuneda M et al (2004) Detection of phospholipase D on solid materials. Anal Biochem 329:157–159
McDermott M, Wakelam MJ, Morris AJ (2004) Phospholipase D. Biochem Cell Biol 82:225–253
Leiros I, Secundo F, Zambonelli C et al (2000) The first crystal structure of a phospholipase D. Structure 8:655–667
Liscovitch M, Czarny M, Fiucci G et al (2000) Phospholipase D: molecular and cell biology of a novel gene family. Biochem J 345(Pt 3):401–415
McNamara PJ, Cuevas WA, Songer JG (1995) Toxic phospholipases D of Corynebacterium pseudotuberculosis. C. ulcerans and Arcanobacterium haemolyticum: cloning and sequence homology. Gene 156:113–118
Shimizu T, Ohto T, Kita Y (2006) Cytosolic phospholipase A2: biochemical properties and physiological roles. IUBMB Life 58:328–333
Clausen K (2001) Enzymatic oil-degumming by a novel microbial phospholipase. Eur J Lipid Sci Technol 103:333–340
MacRitchie F (1977) Flour lipids and their effects in baking. J Sci Food Agric 28:53–58
Dutilh CE, Groger W (1981) Improvement of product attributes of mayonnaise by enzymic hydrolysis of egg yolk with phospholipase A2. J Sci Food Agric 32:451–458
Daimer K, Kulozik U (2008) Impact of a treatment with phospholipase A2 on the physicochemical properties of Hen Egg yolk. J Agric Food Chem 56:4172–4180
Nebesny E, Rosicka J, Pierzgalski T (1998) Enzymatic hydrolysis of wheat starch into glucose. Starch - Stärke 50:337–341
Lilbæk HM, Broe ML, Høier E et al (2006) Improving the yield of mozzarella cheese by phospholipase treatment of milk. J Dairy Sci 89:4114–4125
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media New York
About this protocol
Cite this protocol
Aloulou, A., Ali, Y.B., Bezzine, S., Gargouri, Y., Gelb, M.H. (2012). Phospholipases: An Overview. In: Sandoval, G. (eds) Lipases and Phospholipases. Methods in Molecular Biology, vol 861. Humana Press. https://doi.org/10.1007/978-1-61779-600-5_4
Download citation
DOI: https://doi.org/10.1007/978-1-61779-600-5_4
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-61779-599-2
Online ISBN: 978-1-61779-600-5
eBook Packages: Springer Protocols