Phospholipase A₂ (PLA₂, EC 3.1.1.4) cleaves the sn-2 fatty acid of phospholipids, primarily phosphatidylcholine, to generate lysophosphatidylcholine and arachidonic acid. Most commonly-used inhibitors (e.g. bromoenol lactone, arachidonyl trifluoromethyl ketone or methyl arachidonyl fluorophosphonate) are either non-selective within the family of phospholipase A₂ enzymes or have activity against other eicosanoid-metabolising enzymes.

Secreted or extracellular forms: sPLA₂-1B, sPLA₂-2A, sPLA₂-2D, sPLA₂-2E, sPLA₂-2F, sPLA₂-3, sPLA₂-10 and sPLA₂-12A

Cytosolic, calcium-dependent forms: cPLA₂-4A, cPLA₂-4B, cPLA₂-4C, cPLA₂-4D, cPLA₂-4E and cPLA₂-4F

Other forms: PLA₂-G5, iPLA₂-G6, PLA₂-G7 and PAFAH2 (platelet-activating factor acetylhydrolase 2)

The sequence of PLA₂-2C suggests a lack of catalytic activity, while PLA₂-12B (GXIIB, GXIII sPLA₂-like) appears to be catalytically inactive [7]. A further fragment has been identified with sequence similarities to Group II PLA₂ members. Otoconin 90 (OC90) shows sequence homology to PLA₂-G10.

A binding protein for secretory phospholipase A₂ has been identified which shows modest selectivity for sPLA₂-1B over sPLA₂-2A, and also binds snake toxin phospholipase A₂ [1]. The binding protein appears to have clearance function for circulating secretory phospholipase A₂, as well as signalling functions, and is a candidate antigen for idiopathic membraneous nephropathy [2].

PLA₂-G7 and PAFAH2 also express platelet-activating factor acetylhydrolase activity (EC 3.1.1.47).

* Key recommended reading is highlighted with an asterisk

* Astudillo AM, Balboa MA, Balsinde J. (2019) Selectivity of phospholipid hydrolysis by phospholipase A2 enzymes in activated cells leading to polyunsaturated fatty acid mobilization. Biochim Biophys Acta Mol Cell Biol Lipids, 1864 (6): 772-783. [PMID:30010011]

* Khan MI, Hariprasad G. (2020) Human Secretary Phospholipase A2 Mutations and Their Clinical Implications. J Inflamm Res, 13: 551-561. DOI: 10.2147/JIR.S269557 [PMID:32982370]

* Kita Y, Shindou H, Shimizu T. (2019) Cytosolic phospholipase A2 and lysophospholipid acyltransferases. Biochim Biophys Acta Mol Cell Biol Lipids, 1864 (6): 838-845. [PMID:30905348]

Leslie CC. (2015) Cytosolic phospholipase A₂: physiological function and role in disease. J Lipid Res, 56 (8): 1386-402. [PMID:25838312]

* Mouchlis VD, Dennis EA. (2019) Phospholipase A2 catalysis and lipid mediator lipidomics. Biochim Biophys Acta Mol Cell Biol Lipids, 1864 (6): 766-771. [PMID:30905345]

* Murakami M, Miki Y, Sato H, Murase R, Taketomi Y, Yamamoto K. (2019) Group IID, IIE, IIF and III secreted phospholipase A2s. Biochim Biophys Acta Mol Cell Biol Lipids, 1864 (6): 803-818. [PMID:30905347]

Ong WY, Farooqui T, Kokotos G, Farooqui AA. (2015) Synthetic and natural inhibitors of phospholipases A2: their importance for understanding and treatment of neurological disorders. ACS Chem Neurosci, 6 (6): 814-31. [PMID:25891385]

Ramanadham S, Ali T, Ashley JW, Bone RN, Hancock WD, Lei X. (2015) Calcium-independent phospholipases A2 and their roles in biological processes and diseases. J Lipid Res, 56 (9): 1643-68. [PMID:26023050]

* Samuchiwal SK, Balestrieri B. (2019) Harmful and protective roles of group V phospholipase A2: Current perspectives and future directions. Biochim Biophys Acta Mol Cell Biol Lipids, 1864 (6): 819-826. [PMID:30308324]

* Shayman JA, Tesmer JJG. (2019) Lysosomal phospholipase A2. Biochim Biophys Acta Mol Cell Biol Lipids, 1864 (6): 932-940. [PMID:30077006]

* van Hensbergen VP, Wu Y, van Sorge NM, Touqui L. (2020) Type IIA Secreted Phospholipase A2 in Host Defense against Bacterial Infections. Trends Immunol, 41 (4): 313-326. DOI: 10.1016/j.it.2020.02.003 [PMID:32151494]

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