Phospholipase A2 enzymes in eicosanoid generation.
Phospholipase A2 (PLA2) enzymes cleave esterified fatty acids from membrane glycerophospholipids. The 20-carbon polyunsaturated fatty acid, arachidonic acid, is used as substrate by intermediate enzymes for the generation of eicosanoids, including leukotrienes and prostanoid products. An expanding number of PLA2 enzymes has now been identified that may participate in arachidonic acid release and thus serve a rate-limiting role in eicosanoid biosynthesis. Cellular PLA2 function for various members is regulated by constitutive or elicited expression, as well as by posttranslational events such as phosphorylation. In addition, the function of some cellular PLA2 enzymes is regulated by a requirement for calcium or by localization to a particular subcellular compartment. Finally, some PLA2 enzymes are secreted from the cell where they may directly interact with plasma membrane or transmembrane receptors to function as autocrine or paracrine mediators. Evaluating the roles of a number of these functionally similar PLA2 enzymes in the biosynthesis of leukotrienes and other eicosanoids is the focus of this review.
Bingham
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Department of Medicine, Harvard Medical School, Boston, MA, USA.
Austen
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D000595:Amino Acid Sequence; D000818:Animals; D002451:Cell Compartmentation; D003600:Cytosol / Q000201:enzymology; D015777:Eicosanoids / Q000096:biosynthesis*; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D008322:Mammals / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000502:physiology; D010741:Phospholipases A / Q000145:classification / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D054507:Receptors, Phospholipase A2; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D020298:U937 Cells / Q000201:enzymology
D015777:Eicosanoids; D007527:Isoenzymes; D008563:Membrane Lipids; D009363:Neoplasm Proteins; C516360:PLA2R1 protein, human; D010743:Phospholipids; C516357:Pla2r1 protein, mouse; D011956:Receptors, Cell Surface; D054507:Receptors, Phospholipase A2; D010741:Phospholipases A; D054467:Phospholipases A2