W6 a1 human pathophysiology

Chapter 1 Myofascial Trigger Points The Sensitive Nervous System.

W6 a1 human pathophysiology

This particular phospholipase specifically recognizes the sn-2 acyl bond of phospholipids and catalytically hydrolyzes the bond, releasing arachidonic acid and lysophosphatidic acid.

W6 a1 human pathophysiology

Upon downstream modification by cyclooxygenasesarachidonic acid is modified into active compounds called eicosanoids. Eicosanoids include prostaglandins and leukotrieneswhich are categorized as anti-inflammatory and inflammatory mediators.

Due to the W6 a1 human pathophysiology 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 A1phospholipase Bphospholipase Cand phospholipase D.

W6 a1 human pathophysiology

Two most notable families are secreted and cytosolic phospholipases A2. Secreted phospholipases A2 sPLA2 The extracellular forms of phospholipases A2 have been isolated from different venoms snakebeeand waspfrom 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. This arachidonic acid is then metabolized to form several inflammatory and thrombogenic molecules.

Excess levels of sPLA2 is thought to contribute to several inflammatory diseasesand 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.

They include a C2 domain and a large catalytic domain. These phospholipases are involved in cell signaling processes, such as inflammatory response. They release arachidonic acid from membrane phospholipids. Arachidonic acid is both a signaling molecule and the precursor for the synthesis of other signaling molecules termed eicosanoids.

These include leukotrienes and prostaglandins. Some eicosanoids are synthesized from diacylglycerolreleased from the lipid bilayer by phospholipase C see below.

Phospholipases A2 can be classified based on sequence homology. The calcium ion polarizes the sn-2 carbonyl oxygen while also coordinating with a catalytic water molecule, w5. His 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 is thought to be enhanced through hydrogen bonding with Asp 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 constantof 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. Close-up rendering of PLA2 active site with phosphate enzyme inhibitor.

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Calcium ion pink coordinates with phosphate light blue. Phosphate mimics tetrahedral intermediate blocking substrate access to active site. HisAsp, and 2 water molecules are also shown.Background.

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