Phospholipase a2
Inflammation and Regeneration volume 36Article number: 7 Cite this article. Metrics details. Within the phospholipase A 2 PLA 2 superfamily that hydrolyzes phospholipids to yield fatty acids and lysophospholipids, the secreted PLA 2 sPLA 2 enzymes comprise the largest family that contains 11 isoforms in mammals. Individual sPLA 2 s exhibit unique distributions and specific phospholipase a2 properties, suggesting their distinct biological roles, phospholipase a2.
Federal government websites often end in. The site is secure. The phospholipase A 2 PLA 2 superfamily consists of many different groups of enzymes that catalyze the hydrolysis of the sn-2 ester bond in a variety of different phospholipids. The products of this reaction, a free fatty acid, and lysophospholipid have many different important physiological roles. This review focuses on the superfamily of PLA 2 enzymes, and then uses three specific examples of these enzymes to examine the differing biochemistry of the three main types of these enzymes.
Phospholipase a2
The enzyme phospholipase A 2 EC 3. This particular phospholipase specifically recognizes the sn 2 acyl bond of phospholipids and catalytically hydrolyzes the bond, releasing arachidonic acid and lysophosphatidic acid. Upon downstream modification by cyclooxygenases or lipoxygenases , arachidonic acid is modified into active compounds called eicosanoids. Eicosanoids include prostaglandins and leukotrienes , which are categorized as anti-inflammatory and inflammatory mediators. PLA2 enzymes are commonly found in mammalian tissues as well as arachnid, insect, and snake venom. 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. Additional types of phospholipases include phospholipase A 1 , phospholipase B , phospholipase C , and phospholipase D. Phospholipases A 2 include several unrelated protein families with common enzymatic activity. Two most notable families are secreted and cytosolic phospholipases A 2. The extracellular forms of phospholipases A 2 have been isolated from different venoms snake , [5] bee , and wasp , from virtually every studied mammalian tissue including pancreas and kidney as well as from bacteria. Pancreatic sPLA2 serve for the initial digestion of phospholipid compounds in dietary fat. Venom phospholipases help to immobilize prey by promoting cell lysis [ citation needed ].
The PLA 2 activity of the enzyme is active against monomeric substrate, phospholipase a2 there is a substantial activation upon binding a membrane surface [ 75 ]. Abe A, Shayman JA, phospholipase a2. Ceramide 1-phosphate C1P binds to the enzyme at a specific site in the C2 domain consisting of Arg, Lys, and Arg shown in Fig.
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Federal government websites often end in. Before sharing sensitive information, make sure you're on a federal government site. The site is secure. NCBI Bookshelf. Jarett Casale ; Salah Eddine O. Kacimi ; Matthew Varacallo. Kacimi 2 ; Matthew Varacallo 3.
Phospholipase a2
Federal government websites often end in. The site is secure. The data presented in this review were compiled from the cited work.
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August Kumoanogoh University of Osaka, Japan for providing an opportunity to write this manuscript. Distinct roles of two intracellular phospholipase A2s in fatty acid release in the cell death pathway. Inflammation and Regeneration volume 36 , Article number: 7 Cite this article. Further knowledge of this superfamily of enzymes should raise the potential for many possible new and exciting drug targets in the years to come. An asparagine substitution for His 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. Hydrolase : esterases EC 3. Molecular characterization of cytosolic phospholipase A2-beta. Article PubMed Google Scholar. Inflammation and metabolic disorders. PLA 2 hydrolyzes the sn -2 position of glycerophospholipids to yield fatty acids typically unsaturated and lysophospholipids. All of the sPLA 2 enzymes except group III [ 14 ] display a characteristic increase in activity when substrate is switched from monomeric to higher ordered lipid aggregates, and this is known as interfacial activation [ 15 ].
The enzyme phospholipase A 2 EC 3. This particular phospholipase specifically recognizes the sn 2 acyl bond of phospholipids and catalytically hydrolyzes the bond, releasing arachidonic acid and lysophosphatidic acid. Upon downstream modification by cyclooxygenases or lipoxygenases , arachidonic acid is modified into active compounds called eicosanoids.
The enzyme contains the six conserved disulfide bonds from 28—44, 26—, 43—99, 50—92, 60—85, and 78—80, as well as the additional disulfide bridge from 11—71 [ 39 ]. Methylation of histidine in pancreatic phospholipase A2. Odegaard JI, Chawla A. In this review, we summarize our current knowledge of the roles of sPLA 2 s in metabolic disorders including obesity, hepatic steatosis, diabetes, insulin resistance, and adipose tissue inflammation. Pharmacological Reviews. A reinvestigation. Although the reason for the discrepancy between the two studies is unclear, it might have arisen from different experimental conditions HFD versus chow diets or female versus male mice in different animal facilities. Arterioscler Thromb Vasc Biol. Bee venom phospholipase A 2 sPLA2. In the case of an inflammation, the application of glucocorticoids up-regulate mediated at the gene level the production of the protein lipocortin which may inhibit cPLA2 and reduce the inflammatory response. Acylglycerol transacylase, triacylglycerol lipase. The first cytosolic PLA 2 was isolated from neutrophils and platetlets in The antibacterial properties of secreted phospholipases A 2 Biochim Biophys Acta. Recently, it has become clear that several sPLA 2 s are expressed in the adipose tissue or gastrointestinal GI tract and have variable influences on systemic metabolic states [ 18 — 20 ]. Conclusions It is now obvious that at least four sPLA 2 s are involved in metabolic regulation through distinct mechanisms, as summarized below.
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