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Phospholipases A2 (PLA2s) EC 3.1.1.4 are enzymes that release fatty acids from the second carbon group of glycerol. This particular phospholipase specifically recognizes the sn-2 acyl bond of phospholipids and catalytically hydrolyzes the bond releasing arachidonic acid and lysophospholipids. Upon downstream modification by cyclooxygenases, arachidonic acid is modified into active compounds called eicosanoids. Eicosanoids include prostaglandins and leukotrienes, which are categorized as anti-inflammatory and inflammatory mediators.^[1]

PLA2 are commonly found in mammalian tissues as well as insect and snake venom.^[2] Venom from both snakes and insects is largely composed of melittin, which is a stimulant of PLA2. Due to the increased presence and activity of PLA2 resulting from a snake or insect bite, arachidonic acid is released from the phospholipid membrane disproportionately. As a result, inflammation and pain occur at the site.^[3] There are also prokaryotic A2 phospholipases.

Additional types of phospholipases include phospholipase A1, phospholipase B, phospholipase C, and phospholipase D.^[4]

Families

Phospholipases A2 include several unrelated protein families with common enzymatic activity. Two most notable families are secreted and cytosolic phospholipases A2. Other families include Ca²⁺ independent PLA2 (iPLA2) and lipoprotein-associated PLA2s (lp-PLA2), also known as platelet activating factor acetylhydrolase (PAF-AH).

Secreted phospholipases A2 (sPLA2)

The extracellular forms of phospholipases A2 have been isolated from different venoms (snake, bee, and wasp), from virtually every studied mammalian tissue (including pancreas and kidney) as well as from bacteria. They require Ca²⁺ for activity.

Pancreatic sPLA2 serve for the initial digestion of phospholipid compounds in dietary fat. Venom phospholipases help to immobilize prey by promoting cell lysis.

In mice, group III sPLA2 are involved in sperm maturation,^[5] and group X are thought to be involved in sperm capacitation.^[6]

sPLA2 has been shown to promote inflammation in mammals by catalyzing the first step of the arachidonic acid pathway by breaking down phospholipids, resulting in the formation of fatty acids including arachidonic acid. This arachidonic acid is then metabolized to form several inflammatory and thrombogenic molecules. Excess levels of sPLA2 is thought to contribute to several inflammatory diseases, and has been shown to promote vascular inflammation correlating with coronary events in coronary artery disease and acute coronary syndrome,^[7] and possibly leading to acute respiratory distress syndrome^[8] and progression of tonsillitis^[9]

in children. In mice, excess levels of sPLA2 have been associated with inflammation thought to exacerbate asthma^[10] and ocular surface inflammation (dry eye).^[11]

Increased sPLA2 activity is observed in the cerebrospinal fluid of humans with Alzheimer's disease and multiple sclerosis, and may serve as a marker of increases in permeability of the blood-cerebrospinal fluid barrier.^[12]

Cytosolic phospholipases A2 (cPLA2)

The intracellular PLA2 are also Ca-dependent, but they have completely different 3D structure and significantly larger than secreted PLA2 (more than 700 residues). They include C2 domain and large catalytic domain.

These phospholipases are involved in cell signaling processes, such as inflammatory response. The produced arachidonic acid is both a signaling molecule and the precursor for other signaling molecules termed eicosanoids. These include leukotrienes and prostaglandins. Some eicosanoids are synthesized from diacylglycerol, released from the lipid bilayer by phospholipase C (see below).

Phospholipases A2 can be classified based on sequence homology.^[13]

Lipoprotein-associated PLA2s (lp-PLA2)

Increased levels of lp-PLA2 are associated with cardiac disease, and may contribute to atherosclerosis.^[14]

Mechanism

The suggested catalytic mechanism of pancreatic sPLA2 is initiated by a His-48/Asp-99/calcium complex within the active site. The calcium ion polarizes the sn-2 carbonyl oxygen while also coordinating with a catalytic water molecule, w5. His-48 improves the nucleophilicity of the catalytic water via a bridging second water molecule, w6. It has been suggested that two water molecules are necessary to traverse the distance between the catalytic histidine and the ester. The basicity of His-48 is thought to be enhanced through hydrogen bonding with Asp-99. An asparagine substitution for His-48 maintains wild-type activity, as the amide functional group on asparagine can also function to lower the pKa, or acid dissociation constant, of the bridging water molecule. The rate limiting state is characterized as the degradation of the tetrahedral intermediate composed of a calcium coordinated oxyanion. The role of calcium can also be duplicated by other relatively small cations like cobalt and nickel.^[15] Before becoming active in digestion, the proform of PLA2 is activated by Trypsin.

Close-up rendering of PLA2 active site with phosphate enzyme inhibitor. Calcium ion (pink) coordinates with phosphate (light blue). Phosphate mimics tetrahedral intermediate blocking substrate access to active site. His-48, Asp-99, and 2 water molecules are also shown.^[16]

Mechanism of hydrolysis catalyzed by PLA2

PLA2 can also be characterized as having a channel featuring a hydrophobic wall in which hydrophobic amino acid residues such as Phe, Leu, and Tyr serve to bind the substrate. Another component of PLA2 is the seven disulfide bridges that are influential in regulation and stable protein folding.^[15]

Regulation

Due to the importance of PLA2 in inflammatory responses, regulation of the enzyme is essential. PLA2 is regulated by phosphorylation and calcium concentrations. PLA2 is phosphorylated by a MAPK at Serine-505. When phosphorylation is coupled with an influx of calcium ions, PLA2 becomes stimulated and can translocate to the membrane to begin catalysis.^[17]

Phosphorylation of PLA2 may be a result of ligand binding to receptors, including:

5-HT2 receptors ^[18]
mGLUR1^[18]
bFGF receptor^[18]
IFN-α receptor^[18]
IFN-γ receptor^[18]

In the case of an inflammation the application of glucocorticoids will stimulate the release of the protein lipocortin which will inhibit PLA2 and reduce the inflammatory response.

Relevance in Neurological Disorders

In normal brain cells, PLA2 regulation accounts for a balance between arachidonic acid's conversion into proinflammatory mediators and its reincorporation into the membrane. In the absence of strict regulation of PLA2 activity, a disproportionate amount of proinflammatory mediators are produced. The resulting induced oxidative stress and neuroinflammation is analogous to neurological diseases such as Alzheimer's disease, epilepsy, multiple sclerosis, ischemia. Lysophospholipids are another class of molecules released from the membrane that are upstream predecessors of platelet activating factors (PAF). Abnormal levels of potent PAF are also associated with neurological damage. An optimal enzyme inhibitor would specifically target PLA2 activity on neural cell membranes already under oxidative stress and potent inflammation. Thus, specific inhibitors of brain PLA2 could be a pharmaceutical approach to treatment of several disorders associated with neural trauma.^[19]

Increase in phospholipase A2 activity is an acute-phase reaction that rises during inflammation, which is also seen to be exponentially higher in low back disc herniations compared to rheumatoid arthritis.^{[citation needed]} It is a mixture of inflammation and substance P that are responsible for pain.^{[citation needed]}

Increased phospholipase A2 has also been associated with neuropsychiatric disorders such as schizophrenia and pervasive developmental disorders (such as autism), though the mechanisms involved are not known.^[20]

Isozymes

Human phospholipase A2 isozymes include:

Group I: PLA2G1B
Group II: PLA2G2A, PLA2G2C, PLA2G2D, PLA2G2E, PLA2G2F
Group III: PLA2G3
Group IV: PLA2G4A, PLA2G4B, PLA2G4C, PLA2G4D, PLA2G4E, PLA2G4F
Group V: PLA2G5
Group VI: PLA2G6
Group VII: PLA2G7
Group X: PLA2G10
Group XII: PLA2G12A, PLA2G12B

In addition, the following human proteins contain the phospholipase A2 domain:

OC90

References

^ Dennis EA (May 1994). "Diversity of group types, regulation, and function of phospholipase A2". The Journal of Biological Chemistry 269 (18): 13057–60. PMID 8175726.
^ Nicolas JP, Lin Y, Lambeau G, Ghomashchi F, Lazdunski M, Gelb MH (Mar 1997). "Localization of structural elements of bee venom phospholipase A2 involved in N-type receptor binding and neurotoxicity". The Journal of Biological Chemistry 272 (11): 7173–81. doi:10.1074/jbc.272.11.7173. PMID 9054413.
^ Argiolas A, Pisano JJ (Nov 1983). "Facilitation of phospholipase A2 activity by mastoparans, a new class of mast cell degranulating peptides from wasp venom" (PDF). The Journal of Biological Chemistry 258 (22): 13697–702. PMID 6643447.
^ Cox, Michael; Nelson, David R.; Lehninger, Albert L (2005). Lehninger principles of biochemistry (4th ed.). San Francisco: W.H. Freeman. ISBN 0-7167-4339-6.
^ Sato H, Taketomi Y, Isogai Y, Miki Y, Yamamoto K, Masuda S, Hosono T, Arata S, Ishikawa Y, Ishii T, Kobayashi T, Nakanishi H, Ikeda K, Taguchi R, Hara S, Kudo I, Murakami M (May 2010). "Group III secreted phospholipase A2 regulates epididymal sperm maturation and fertility in mice". The Journal of Clinical Investigation 120 (5): 1400–14. doi:10.1172/JCI40493. PMC 2860917. PMID 20424323.
^ Escoffier J, Jemel I, Tanemoto A, Taketomi Y, Payre C, Coatrieux C, Sato H, Yamamoto K, Masuda S, Pernet-Gallay K, Pierre V, Hara S, Murakami M, De Waard M, Lambeau G, Arnoult C (May 2010). "Group X phospholipase A2 is released during sperm acrosome reaction and controls fertility outcome in mice". The Journal of Clinical Investigation 120 (5): 1415–28. doi:10.1172/JCI40494. PMC 2860919. PMID 20424324.
^ Mallat Z, Lambeau G, Tedgui A (Nov 2010). "Lipoprotein-associated and secreted phospholipases A₂ in cardiovascular disease: roles as biological effectors and biomarkers". Circulation 122 (21): 2183–200. doi:10.1161/CIRCULATIONAHA.110.936393. PMID 21098459.
^ De Luca D, Minucci A, Cogo P, Capoluongo ED, Conti G, Pietrini D, Carnielli VP, Piastra M (Jan 2011). "Secretory phospholipase A₂ pathway during pediatric acute respiratory distress syndrome: a preliminary study". Pediatric Critical Care Medicine 12 (1): e20–4. doi:10.1097/PCC.0b013e3181dbe95e. PMID 20351613.
^ Ezzeddini R, Darabi M, Ghasemi B, Jabbari Moghaddam Y, Jabbari Y, Abdollahi S, Rashtchizadeh N, Gharahdaghi A, Darabi M, Ansarin M, Shaaker M, Samadi A, Karamravan J (Apr 2012). "Circulating phospholipase-A2 activity in obstructive sleep apnea and recurrent tonsillitis". International Journal of Pediatric Otorhinolaryngology 76 (4): 471–4. doi:10.1016/j.ijporl.2011.12.026. PMID 22297210.
^ Henderson WR, Oslund RC, Bollinger JG, Ye X, Tien YT, Xue J, Gelb MH (Aug 2011). "Blockade of human group X secreted phospholipase A2 (GX-sPLA2)-induced airway inflammation and hyperresponsiveness in a mouse asthma model by a selective GX-sPLA2 inhibitor". The Journal of Biological Chemistry 286 (32): 28049–55. doi:10.1074/jbc.M111.235812. PMC 3151050. PMID 21652694.
^ Wei Y, Epstein SP, Fukuoka S, Birmingham NP, Li XM, Asbell PA (Jun 2011). "sPLA2-IIa amplifies ocular surface inflammation in the experimental dry eye (DE) BALB/c mouse model". Investigative Ophthalmology & Visual Science 52 (7): 4780–8. doi:10.1167/iovs.10-6350. PMC 3175946. PMID 21519031.
^ Chalbot S, Zetterberg H, Blennow K, Fladby T, Andreasen N, Grundke-Iqbal I, Iqbal K (January 2011). "Blood-cerebrospinal fluid barrier permeability in Alzheimer's disease". Journal of Alzheimer's Disease 25 (3): 505–15. doi:10.3233/JAD-2011-101959 (inactive 2015-02-01). PMC 3139450. PMID 21471645.
^ Six DA, Dennis EA (Oct 2000). "The expanding superfamily of phospholipase A(2) enzymes: classification and characterization". Biochimica Et Biophysica Acta 1488 (1-2): 1–19. doi:10.1016/S1388-1981(00)00105-0. PMID 11080672.
^ Wilensky RL, Shi Y, Mohler ER, Hamamdzic D, Burgert ME, Li J, Postle A, Fenning RS, Bollinger JG, Hoffman BE, Pelchovitz DJ, Yang J, Mirabile RC, Webb CL, Zhang L, Zhang P, Gelb MH, Walker MC, Zalewski A, Macphee CH (Oct 2008). "Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development". Nature Medicine 14 (10): 1059–66. doi:10.1038/nm.1870. PMC 2885134. PMID 18806801.
^ ^a ^b Berg OG, Gelb MH, Tsai MD, Jain MK (Sep 2001). "Interfacial enzymology: the secreted phospholipase A(2)-paradigm". Chemical Reviews 101 (9): 2613–54. doi:10.1021/cr990139w. PMID 11749391. See page 2640
^ PDB: 1FXF ; Pan YH, Epstein TM, Jain MK, Bahnson BJ; Epstein; Jain; Bahnson (January 2001). "Five coplanar anion binding sites on one face of phospholipase A2: relationship to interface binding". Biochemistry 40 (3): 609–17. doi:10.1021/bi002514g. PMID 11170377.
^ Leslie CC (Jul 1997). "Properties and regulation of cytosolic phospholipase A2". The Journal of Biological Chemistry 272 (27): 16709–12. doi:10.1074/jbc.272.27.16709. PMID 9201969.
^ ^a ^b ^c ^d ^e Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 103. ISBN 1-4160-2328-3.
^ Farooqui AA, Ong WY, Horrocks LA (Sep 2006). "Inhibitors of brain phospholipase A2 activity: their neuropharmacological effects and therapeutic importance for the treatment of neurologic disorders". Pharmacological Reviews 58 (3): 591–620. doi:10.1124/pr.58.3.7. PMID 16968951.
^ Bell JG, MacKinlay EE, Dick JR, MacDonald DJ, Boyle RM, Glen AC (Oct 2004). "Essential fatty acids and phospholipase A2 in autistic spectrum disorders". Prostaglandins, Leukotrienes, and Essential Fatty Acids 71 (4): 201–4. doi:10.1016/j.plefa.2004.03.008. PMID 15301788.

External links

Phospholipase A2 at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 膜性腎症の原因および診断 causes and diagnosis of membranous nephropathy
2. アテローム性動脈硬化症の病因 pathogenesis of atherosclerosis
3. 心血管疾患の危険因子の概要 overview of the possible risk factors for cardiovascular disease
4. 鎌状赤血球症を伴う成人における急性胸部症候群 acute chest syndrome in adults with sickle cell disease
5. 肺高血圧症の病因 pathogenesis of pulmonary hypertension

English Journal

Lupine protein hydrolysates inhibit enzymes involved in the inflammatory pathway.

Millán-Linares Mdel C1, Yust Mdel M2, Alcaide-Hidalgo JM1, Millán F1, Pedroche J1.Author information 1Instituto de la Grasa-CSIC, Av. Padre García Tejero, 4, 41012 Sevilla, Spain.2Facultad de Química, Universidad de Sevilla, C/Prof. García González, 1, 41012 Sevilla, Spain. Electronic address: mdmar@cica.es.AbstractLupine protein hydrolysates (LPHs) were obtained from a lupine protein isolate (LPI) by enzymatic hydrolysis using two proteases, Izyme AL and Alcalase 2.4 L, and their potential anti-inflammatory capacities were studied by determining their in vitro inhibition of the following enzymes that are involved in the inflammatory process: phospholipase A2 (PLA2), cyclooxygenase 2 (COX-2), thrombin, and transglutaminase (TG). The strongest inhibitory activities toward PLA2 and TG were found in the hydrolysates obtained by hydrolysis with Izyme and subsequently with Alcalase, with more than 70% inhibition obtained in some cases. All of the hydrolysates tested inhibited more than 60% of the COX-2 activity. In no case did the percentage of thrombin activity inhibition exceed 40%. The best inhibitory activities were found in the LPH obtained after 15 min of hydrolysis with Alcalase and in the LPH obtained after 60 min of hydrolysis with Izyme followed by 15 min of hydrolysis with Alcalase. Enzyme kinetic analyses were conducted to determine the Km and Vmax parameters of these two hydrolysates using the Lineweaver-Burk equation. Both hydrolysates competitively inhibited the thrombin and PLA2 activities. In the case of COX-2 and TG, the inhibition appeared to be the mixed type.
Food chemistry.Food Chem.2014 May 15;151:141-7. doi: 10.1016/j.foodchem.2013.11.053. Epub 2013 Nov 19.
Lupine protein hydrolysates (LPHs) were obtained from a lupine protein isolate (LPI) by enzymatic hydrolysis using two proteases, Izyme AL and Alcalase 2.4 L, and their potential anti-inflammatory capacities were studied by determining their in vitro inhibition of the following enzymes that are invo
PMID 24423513

Neurotoxicity of coral snake phospholipases A2 in cultured rat hippocampal neurons.

de Carvalho ND1, Garcia RC2, Kleber Ferreira A3, Rodrigo Batista D4, Carlos Cassola A4, Maria D3, Lebrun I3, Mendes Carneiro S5, Castro Afeche S1, Marcourakis T2, Sandoval MR6.Author information 1Laboratory of Pharmacology, Butantan Institute, Av. Dr. Vital Brasil 1500, São Paulo, SP 05503 900, Brazil.2Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP 05508 000, Brazil.3Laboratory of Biochemistry and Biophysics, Butantan Institute, São Paulo, SP 05503 900, Brazil.4Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.5Laboratory of Cellular Biology, Butantan Institute, São Paulo, SP 05503 900, Brazil.6Laboratory of Pharmacology, Butantan Institute, Av. Dr. Vital Brasil 1500, São Paulo, SP 05503 900, Brazil. Electronic address: mrlsando@usp.br.AbstractThe neurotoxicity of two secreted Phospholipases A2 from Brazilian coral snake venom in rat primary hippocampal cell culture was investigated. Following exposure to Mlx-8 or Mlx-9 toxins, an increase in free cytosolic Ca(2+) and a reduction in mitochondrial transmembrane potential (ΔΨm) became evident and occurred prior to the morphological changes and cytotoxicity. Exposure of hippocampal neurons to Mlx-8 or Mlx-9 caused a decrease in the cell viability as assessed by MTT and LDH assays. Inspection using fluorescent images and ultrastructural analysis by scanning and transmission electron microscopy showed that multiphase injury is characterized by overlapping cell death phenotypes. Shrinkage, membrane blebbing, chromatin condensation, nucleosomal DNA fragmentation and the formation of apoptotic bodies were observed. The most striking alteration observed in the electron microscopy was the fragmentation and rarefaction of the neuron processes network. Degenerated terminal synapses, cell debris and apoptotic bodies were observed among the fragmented fibers. Numerous large vacuoles as well as swollen mitochondria and dilated Golgi were noted. Necrotic signs such as a large amount of cellular debris and membrane fragmentation were observed mainly when the cells were exposed to highest concentration of the PLA2-neurotoxins. PLA2s exposed cultures showed cytoplasmic vacuoles filled with cell debris, clusters of mitochondria presented mitophagy-like structures that are in accordance to patterns of programmed cell death by autophagy. Finally, we demonstrated that the sPLA2s, Mlx-8 and Mlx-9, isolated from the Micrurus lemniscatus snake venom induce a hybrid cell death with apoptotic, autophagic and necrotic features. Furthermore, this study suggests that the augment in free cytosolic Ca(2+) and mitochondrial dysfunction are involved in the neurotoxicity of Elapid coral snake venom sPLA2s.
Brain research.Brain Res.2014 Mar 13;1552:1-16. doi: 10.1016/j.brainres.2014.01.008. Epub 2014 Jan 27.
The neurotoxicity of two secreted Phospholipases A2 from Brazilian coral snake venom in rat primary hippocampal cell culture was investigated. Following exposure to Mlx-8 or Mlx-9 toxins, an increase in free cytosolic Ca(2+) and a reduction in mitochondrial transmembrane potential (ΔΨm) became evi
PMID 24480475

Transglutaminase 2 and phospholipase A2 interactions in the inflammatory response in human Thp-1 monocytes.

Currò M1, Ferlazzo N, Risitano R, Condello S, Vecchio M, Caccamo D, Ientile R.Author information 1Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, AOU Policlinico "G. Martino", Via C. Valeria, 98125, Messina, Italy.AbstractSeveral experimental approaches have demonstrated that transglutaminase 2 (TG2) increased activity is involved in monocyte activation and inflammatory response. Preliminary results also demonstrate a TG-mediated post-translational modification of phospholipase A2 (PLA2), which catalyzes the release of arachidonic acid from its lipid storage sites. The control of PLA2-mediated production of eicosanoids has been found to be of great benefit for inflammatory disease treatment. However, the identification of the mechanisms of PLA2 activation is a very complex issue, because of the presence of multiple PLA2 forms. The aim of this study was to characterize the interactions between TG2 and sPLA2 in LPS-stimulated THP-1 cells, which were treated with TPA to induce early differentiated macrophage-type model. We demonstrated that increases in TG2 enzyme activity and protein expression may be considered an early event in monocyte/macrophage activation by LPS. Under these conditions, TG2 protein was co-immunoprecipitated with PLA2 by monoclonal antibody directed against the secretory form of the enzyme (sPLA2-V). Concomitantly, the PLA2 enzyme activity increased in TPA-treated cells exposed to LPS; these high levels of enzyme activity were significant reduced by R283, a site-specific inhibitor of TG2. Moreover, confocal laser scanning microscopy analysis of double-immunostained cytochemical specimens confirmed a co-localization of BAPA-labeled proteins and sPLA2-V in LPS-treated cells. These findings give evidence of a complex TG2/sPLA2-V, suggesting the possibility that sPLA2-V is a substrate for TG2. These results demonstrated that TG2 increases produced a sustained activation of PLA2 activity, suggesting a functional interaction between these enzymes in the regulation of inflammatory response.
Amino acids.Amino Acids.2014 Mar;46(3):759-66. doi: 10.1007/s00726-013-1569-y. Epub 2013 Aug 3.
Several experimental approaches have demonstrated that transglutaminase 2 (TG2) increased activity is involved in monocyte activation and inflammatory response. Preliminary results also demonstrate a TG-mediated post-translational modification of phospholipase A2 (PLA2), which catalyzes the release
PMID 23913269

Japanese Journal

膜性腎症とPLA2R抗体 (AYUMI ネフローゼ症候群Update)

秋山真一,丸山彰一
医学のあゆみ 252(11), 1150-1153, 2015-03-14
NAID 40020392704

接触皮膚炎と抗炎症脂質メディエーター (特集皮膚アレルギー疾患の病態解明の進歩)

三木寿美,山本圭,村上誠
臨床免疫・アレルギー科 63(2), 156-163, 2015-02
NAID 40020362698

膜性腎症の最新の知識(PLA2R) (特集新たな腎臓病の知識・治療)

長濱清隆,清水章
成人病と生活習慣病 : 日本成人病(生活習慣病)学会準機関誌 45(1), 42-46, 2015-01
NAID 40020343234

Related Pictures

★リンクテーブル★

拡張検索	「Lp-PLA2」
関連記事	「PL」「PLA」

「Lp-PLA2」

Phospholipase A2
	ee venom phospholipase A2 sPLA2. Middle plane of the lipid bilayer - black dots. Boundary of the hydrocarbon core region - red dots (extracellular side). Layer of lipid phosphates - yellow dots.
Identifiers
Symbol	Phospholip_A2_1
Pfam	PF00068
InterPro	IPR001211
PROSITE	PDOC00109
SCOP	1bbc
SUPERFAMILY	1bbc
OPM superfamily	90
OPM protein	1g4i
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Search
PMC	articles
PubMed	articles
NCBI	proteins

phospholipase A2
	Phospholipase Cleavage Sites. Note that an enzyme that displays both PLA1 and PLA2 activities is called a Phospholipase B
Identifiers
EC number	3.1.1.4
CAS number	9001-84-7
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search
PMC	articles
PubMed	articles
NCBI	proteins

　　[★]

リ・タンパク質関連ホスホリパーゼA2

関: 1-alkyl-2-acetylglycerophosphocholine esterase、lipoprotein-associated phospholipase A2、PAF acetylhydrolase

「PL」

　　[★]

複合感冒薬

PL配合顆粒
総合感冒剤／鎮咳,抗ヒスタミン,解熱配合剤／総合感冒剤

参考

http://www.interq.or.jp/ox/dwm/se/se11/se1180107.html

添付文書

http://www.info.pmda.go.jp/go/pack/1180107D1131_1_02/

「PLA」

　　[★]

[1] Dennis EA (May 1994). "Diversity of group types, regulation, and function of phospholipase A2". The Journal of Biological Chemistry 269 (18): 13057–60. PMID 8175726.

[2] Nicolas JP, Lin Y, Lambeau G, Ghomashchi F, Lazdunski M, Gelb MH (Mar 1997). "Localization of structural elements of bee venom phospholipase A2 involved in N-type receptor binding and neurotoxicity". The Journal of Biological Chemistry 272 (11): 7173–81. doi:10.1074/jbc.272.11.7173. PMID 9054413.

[3] Argiolas A, Pisano JJ (Nov 1983). "Facilitation of phospholipase A2 activity by mastoparans, a new class of mast cell degranulating peptides from wasp venom" (PDF). The Journal of Biological Chemistry 258 (22): 13697–702. PMID 6643447.

[4] Cox, Michael; Nelson, David R.; Lehninger, Albert L (2005). Lehninger principles of biochemistry (4th ed.). San Francisco: W.H. Freeman. ISBN 0-7167-4339-6.

[5] Sato H, Taketomi Y, Isogai Y, Miki Y, Yamamoto K, Masuda S, Hosono T, Arata S, Ishikawa Y, Ishii T, Kobayashi T, Nakanishi H, Ikeda K, Taguchi R, Hara S, Kudo I, Murakami M (May 2010). "Group III secreted phospholipase A2 regulates epididymal sperm maturation and fertility in mice". The Journal of Clinical Investigation 120 (5): 1400–14. doi:10.1172/JCI40493. PMC 2860917. PMID 20424323.

[6] Escoffier J, Jemel I, Tanemoto A, Taketomi Y, Payre C, Coatrieux C, Sato H, Yamamoto K, Masuda S, Pernet-Gallay K, Pierre V, Hara S, Murakami M, De Waard M, Lambeau G, Arnoult C (May 2010). "Group X phospholipase A2 is released during sperm acrosome reaction and controls fertility outcome in mice". The Journal of Clinical Investigation 120 (5): 1415–28. doi:10.1172/JCI40494. PMC 2860919. PMID 20424324.

[pmid21098459-7] Mallat Z, Lambeau G, Tedgui A (Nov 2010). "Lipoprotein-associated and secreted phospholipases A₂ in cardiovascular disease: roles as biological effectors and biomarkers". Circulation 122 (21): 2183–200. doi:10.1161/CIRCULATIONAHA.110.936393. PMID 21098459.

[pmid20351613-8] De Luca D, Minucci A, Cogo P, Capoluongo ED, Conti G, Pietrini D, Carnielli VP, Piastra M (Jan 2011). "Secretory phospholipase A₂ pathway during pediatric acute respiratory distress syndrome: a preliminary study". Pediatric Critical Care Medicine 12 (1): e20–4. doi:10.1097/PCC.0b013e3181dbe95e. PMID 20351613.

[9] Ezzeddini R, Darabi M, Ghasemi B, Jabbari Moghaddam Y, Jabbari Y, Abdollahi S, Rashtchizadeh N, Gharahdaghi A, Darabi M, Ansarin M, Shaaker M, Samadi A, Karamravan J (Apr 2012). "Circulating phospholipase-A2 activity in obstructive sleep apnea and recurrent tonsillitis". International Journal of Pediatric Otorhinolaryngology 76 (4): 471–4. doi:10.1016/j.ijporl.2011.12.026. PMID 22297210.

[10] Henderson WR, Oslund RC, Bollinger JG, Ye X, Tien YT, Xue J, Gelb MH (Aug 2011). "Blockade of human group X secreted phospholipase A2 (GX-sPLA2)-induced airway inflammation and hyperresponsiveness in a mouse asthma model by a selective GX-sPLA2 inhibitor". The Journal of Biological Chemistry 286 (32): 28049–55. doi:10.1074/jbc.M111.235812. PMC 3151050. PMID 21652694.

[pmid21519031-11] Wei Y, Epstein SP, Fukuoka S, Birmingham NP, Li XM, Asbell PA (Jun 2011). "sPLA2-IIa amplifies ocular surface inflammation in the experimental dry eye (DE) BALB/c mouse model". Investigative Ophthalmology & Visual Science 52 (7): 4780–8. doi:10.1167/iovs.10-6350. PMC 3175946. PMID 21519031.

[12] Chalbot S, Zetterberg H, Blennow K, Fladby T, Andreasen N, Grundke-Iqbal I, Iqbal K (January 2011). "Blood-cerebrospinal fluid barrier permeability in Alzheimer's disease". Journal of Alzheimer's Disease 25 (3): 505–15. doi:10.3233/JAD-2011-101959 (inactive 2015-02-01). PMC 3139450. PMID 21471645.

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PLA2