1.02011-09-21 00:25:05 UTC2015-07-21 06:57:31 UTCFDB023127Prostaglandin G2Prostaglandin G2 (PGG2) is synthesized from arachidonic acid on a cyclooxygenase (COX) metabolic pathway as a primary step; the COX biosynthesis of prostaglandin (PG) begins with the highly specific oxygenation of arachidonic acid in the 11R configuration and ends with a 15S oxygenation to form PGG2.
The COX site activity that catalyzes the conversion of arachidonic acid to PGG2 is the target for nonsteroidal antiinflammatory drugs (NSAIDs). The peroxidase site activity catalyzes the two-electron reduction of the hydroperoxide bond of PGG2 to yield the corresponding alcohol prostaglandin H2 (PGH2). The formation of a phenoxyl radical on Tyr385 couples the activities of the two sites. The Tyr385 radical is produced via oxidation by compound I, an oxoferryl porphyrin -cation radical, which is generated by reaction of the hemin resting state with PGG2 or other hydroperoxides. The tyrosyl radical homolytically abstracts the 13proS hydrogen atom of arachidonic acid which initiates a radical cascade that ends with the stereoselective formation of PGG2. PGG2 then migrates from the cyclooxygenase (COX) site to the peroxidase (POX) site where it reacts with the hemin group to generate PGH2 and compound I. The heterolytic oxygen-oxygen bond cleavage is assisted by the conserved distal residues His207 and Gln203, mutation of which has been shown to severely impair enzyme activity. Compound I, upon reaction with Tyr385, gives compound II, which in turn is reduced to the hemin resting state by one-electron oxidation of reducing cosubstrates or undergoes reactions that result in enzyme self-inactivation.
Prostaglandin endoperoxide H synthase (PGHS) 1 is a bifunctional membrane enzyme of the endoplasmic reticulum that converts arachidonic acid into prostaglandin H2 (PGH2), the precursor of all prostaglandins, thromboxanes, and prostacyclins. These lipid mediators are intricately involved in normal physiology, namely, in mitogenesis, fever generation, pain response, lymphocyte chemotaxis, fertility, and contradictory stimuli such as vasoconstriction and vasodilatation, as well as platelet aggregation and quiescence. PGHS is implicated in numerous pathologies, including inflammation, cancers of the colon, lung, and breast, Alzheimer's disease, Parkinson's disease, and numerous cardiovascular diseases including atherosclerosis, thrombosis, myocardial infarction, and stroke. (PMID: 14594816, 16552393, 16411757)
Prostaglandins are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs) and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes) and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent, able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis, through receptor-mediated G-protein linked signaling pathways. [HMDB](5Z)-7-{(1R,4S,5R,6R)-6-[(1E,3S)-3-hydroperoxyoct-1-en-1-yl]-2,3-dioxabicyclo[2.2.1]hept-5-yl}hept-5-enoate(5Z)-7-{(1R,4S,5R,6R)-6-[(1E,3S)-3-hydroperoxyoct-1-en-1-yl]-2,3-dioxabicyclo[2.2.1]hept-5-yl}hept-5-enoic acid9,11-epidioxy-15-hydroperoxy-Prosta-5,13-dien-1-oate9,11-epidioxy-15-hydroperoxy-Prosta-5,13-dien-1-oic acid9S,11R-epidioxy-15S-hydroperoxy-5Z,13E-prostadienoate9S,11R-epidioxy-15S-hydroperoxy-5Z,13E-prostadienoic acidEndoperoxide G2PGG2C20H32O6368.4645368.2198887567-[(1R,4S,5R,6R)-6-[(3S)-3-hydroperoxyoct-1-en-1-yl]-2,3-dioxabicyclo[2.2.1]heptan-5-yl]hept-5-enoic acid7-[(1R,4S,5R,6R)-6-[(3S)-3-hydroperoxyoct-1-en-1-yl]-2,3-dioxabicyclo[2.2.1]heptan-5-yl]hept-5-enoic acid51982-36-6[H]C(=C[C@@]1([H])[C@@]2([H])C[C@]([H])(OO2)[C@]1([H])CC=CCCCC(O)=O)[C@]([H])(CCCCC)OOInChI=1S/C20H32O6/c1-2-3-6-9-15(24-23)12-13-17-16(18-14-19(17)26-25-18)10-7-4-5-8-11-20(21)22/h4,7,12-13,15-19,23H,2-3,5-6,8-11,14H2,1H3,(H,21,22)/t15-,16+,17+,18-,19+/m0/s1SGUKUZOVHSFKPH-BRIYLRKRSA-N belongs to the class of organic compounds known as prostaglandins and related compounds. These are unsaturated carboxylic acids consisting of a 20 carbon skeleton that also contains a five member ring, and are based upon the fatty acid arachidonic acid.Prostaglandins and related compoundsOrganic compoundsLipids and lipid-like moleculesFatty AcylsEicosanoidsAliphatic heteropolycyclic compounds1,2-dioxanes1,2-dioxolanesAlkyl hydroperoxidesAllylic hydroperoxidesCarbonyl compoundsCarboxylic acidsDialkyl peroxidesHeterocyclic fatty acidsHydrocarbon derivativesHydroperoxy fatty acidsLong-chain fatty acidsMonocarboxylic acids and derivativesOxacyclic compoundsPeroxolsUnsaturated fatty acidsAliphatic heteropolycyclic compoundAlkyl hydroperoxideAllylic hydroperoxideCarbonyl groupCarboxylic acidCarboxylic acid derivativeDialkyl peroxideFatty acidHeterocyclic fatty acidHydrocarbon derivativeHydroperoxideHydroperoxy fatty acidLong-chain fatty acidMonocarboxylic acid or derivativesOrganic oxideOrganic oxygen compoundOrganoheterocyclic compoundOrganooxygen compoundOrtho-dioxaneOrtho-dioxolaneOxacyclePeroxolProstaglandin skeletonUnsaturated fatty acidSolidlogp4.31logs-4.15solubility2.64e-02 g/llogp4.41pka_strongest_acidic4.36pka_strongest_basic-4.2iupac7-[(1R,4S,5R,6R)-6-[(3S)-3-hydroperoxyoct-1-en-1-yl]-2,3-dioxabicyclo[2.2.1]heptan-5-yl]hept-5-enoic acidaverage_mass368.4645mono_mass368.219888756smiles[H]C(=C[C@@]1([H])[C@@]2([H])C[C@]([H])(OO2)[C@]1([H])CC=CCCCC(O)=O)[C@]([H])(CCCCC)OOformulaC20H32O6inchiInChI=1S/C20H32O6/c1-2-3-6-9-15(24-23)12-13-17-16(18-14-19(17)26-25-18)10-7-4-5-8-11-20(21)22/h4,7,12-13,15-19,23H,2-3,5-6,8-11,14H2,1H3,(H,21,22)/t15-,16+,17+,18-,19+/m0/s1inchikeySGUKUZOVHSFKPH-BRIYLRKRSA-Npolar_surface_area85.22refractivity99.39polarizability41.3rotatable_bond_count13acceptor_count6donor_count2physiological_charge-1formal_charge0Arachidonic Acid MetabolismSMP00075map00590HMDB0323527647PGX#<Reference:0x00005556747e98a0>#<Reference:0x00005556747e96e8>#<Reference:0x00005556747e9530>#<Reference:0x00005556747e9378>AnatidaeType 1specificAnatidae8830BeefaloType 1specificBos taurus X Bison bison297284BisonType 1specificBison bison9901BuffaloType 1specificBubalus bubalis89462Cattle (Beef, Veal)Type 1specificBos taurus9913ChickenType 1specificGallus gallus9031Columbidae (Dove, Pigeon)Type 1specificColumbidae8930DeerType 1specificCervidae9850Domestic goatType 1specificCapra aegagrus hircus9925Domestic pigType 1specificSus scrofa domestica9825ElkType 1specificCervus canadensis1574408EmuType 1specificDromaius novaehollandiae8790European rabbitType 1specificOryctolagus9984Greylag gooseType 1specificAnser anser8843Guinea henType 1specificNumida meleagris8996HorseType 1specificEquus caballus9796Mallard duckType 1specificAnas platyrhynchos8839Mountain hareType 1specificLepus timidus62621Mule deerType 1specificOdocoileus9871OstrichType 1specificStruthio camelus8801PheasantType 1specificPhasianus colchicus9054QuailType 1specificPhasianidae9005RabbitType 1specificLeporidae9979Rock ptarmiganType 1specificLagopus muta64668Sheep (Mutton, Lamb)Type 1specificOvis aries9940SquabType 1specificColumba8931TurkeyType 1specificMeleagris gallopavo9103Velvet duckType 1specificMelanitta fusca371864Wild boarType 1specificSus scrofa9823