Phospholipase A2

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Bee 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.

Phospholipase Cleavage Sites. Note that an enzyme that displays both PLA1 and PLA2 activities is called a Phospholipase B

Phospholipases A2 (PLA2s) EC 3.1.1.4 are enzymes that specifically hydrolyze the sn-2 fatty acid acyl bond of phospholipids, producing a free fatty acid and a lyso-phospholipid. A large range of fatty acids can be bound to the sn2 position of phospholipids, including arachidonic acid and eicosapentaenoic acid.

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 PLA2 serve for the initial digestion of phospholipid compounds in dietary fat. Venom phospholipases help to immobilize prey by promoting cell lysis.

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 signalling 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.

Genes

• 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

External links

• UMich Orientation of Proteins in Membranes families/superfamily-90 - Secreted phospholipases A2 in the lipid bilayer
• UMich Orientation of Proteins in Membranes families/superfamily-134 - Cytosolic phospholipase A2 and patatin
• MeSH Phospholipase+A2

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