1.02011-09-21 00:28:50 UTC2015-07-21 06:57:39 UTCFDB023370Lipoxin A4Lipoxin A4 (LXA4) was first identified in 1984 by Serhan and colleagues as 5-lipoxygenase interaction product of activated leukocytes. Endogenous transcellular biosynthesis of LXA4 occurs via interaction of leukocytes with epithelium, endothelium or platelets.
Lipoxins (LXs) or the lipoxygenase interaction products are generated from arachidonic acid via sequential actions of lipoxygenases and subsequent reactions to give specific trihydroxytetraene-containing eicosanoids. These unique structures are formed during cell-cell interactions and appear to act at both temporal and spatially distinct sites from other eicosanoids produced during the course of inflammatory responses and to stimulate natural resolution. Lipoxin A4 (LXA4) and lipoxin B4 (LXB4) are positional isomers that each possesses potent cellular and in vivo actions. These LX structures are conserved across species. The results of numerous studies reviewed in this work now confirm that they are the first recognized eicosanoid chemical mediators that display both potent anti-inflammatory and pro-resolving actions in vivo in disease models that include rabbit, rat, and mouse systems. LXs act at specific GPCRs as agonists to regulate cellular responses of interest in inflammation and resolution. Aspirin has a direct impact in the LX circuit by triggering the biosynthesis of endogenous epimers of LX, termed the aspirin-triggered 15-epi-LX, that share the potent anti-inflammatory actions of LX. (PMID: 16005201, 16613568) [HMDB](5S,6R,15S)-Trihydroxy-7,9,13-trans-11-cis-eicosatetraenoate(5S,6R,15S)-Trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acid(5S,6R,7e,9e,11Z,13e,15S)-5,6,15-Trihydroxy-7,9,11,13-eicosatetraenoate(5S,6R,7e,9e,11Z,13e,15S)-5,6,15-Trihydroxy-7,9,11,13-eicosatetraenoic acid(5S,6R,7e,9e,11Z,13e,15S)-5,6,15-Trihydroxyeicosa-7,9,11,13-tetraenoate(5S,6R,7e,9e,11Z,13e,15S)-5,6,15-Trihydroxyeicosa-7,9,11,13-tetraenoic acid(7E,9E,11Z,13E)-(5S,6R,15S)-5,6,15-Trihydroxyicosa-7,9,11,13-tetraenoate(7E,9E,11Z,13E)-(5S,6R,15S)-5,6,15-Trihydroxyicosa-7,9,11,13-tetraenoic acid5(S),6(R),15(S)-Trihydroxyeicosa-7e,9e,11Z,13e-tetraenoate5(S),6(R),15(S)-Trihydroxyeicosa-7e,9e,11Z,13e-tetraenoic acid5S,6R-LipoxinA45S,6R,15S-Trihydroxy-7,9,13-trans-11-cis-eicosatetraenoate5S,6R,15S-Trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acid5S,6R,15S-Trihydroxy-7E,9E,11Z,13E-eicosatetraenoate5S,6R,15S-Trihydroxy-7E,9E,11Z,13E-eicosatetraenoic acid5S,6S-Lipoxin A46R-LXA4LXA4C20H32O5352.4651352.224974134(5S,6R,7E,9E,15S)-5,6,15-trihydroxyicosa-7,9,11,13-tetraenoic acid(5S,6R,7E,9E,15S)-5,6,15-trihydroxyicosa-7,9,11,13-tetraenoic acid89663-86-5[H][C@](O)(CCCCC)C=CC=C\C=C\C=C\[C@@]([H])(O)[C@@]([H])(O)CCCC(O)=OInChI=1S/C20H32O5/c1-2-3-8-12-17(21)13-9-6-4-5-7-10-14-18(22)19(23)15-11-16-20(24)25/h4-7,9-10,13-14,17-19,21-23H,2-3,8,11-12,15-16H2,1H3,(H,24,25)/b6-4?,7-5+,13-9?,14-10+/t17-,18+,19-/m0/s1IXAQOQZEOGMIQS-WZCAPKNJSA-N belongs to the class of organic compounds known as lipoxins. These are eicosanoids with a trihydroxyicosatetraenoic acid skeleton (a c20-fatty acid, with the chain bearing three hydroxyl groups and four double bonds). Lipoxins have four double bonds, which are all conjugated. In some cases a hydroxyl group is substituted by a C=O group.LipoxinsOrganic compoundsLipids and lipid-like moleculesFatty AcylsEicosanoidsAliphatic acyclic compoundsCarbonyl compoundsCarboxylic acidsHydrocarbon derivativesHydroxy fatty acidsLong-chain fatty acidsMonocarboxylic acids and derivativesOrganic oxidesPolyolsSecondary alcoholsUnsaturated fatty acidsAlcoholAliphatic acyclic compoundCarbonyl groupCarboxylic acidCarboxylic acid derivativeFatty acidHydrocarbon derivativeHydroxy fatty acidLipoxinLong-chain fatty acidMonocarboxylic acid or derivativesOrganic oxideOrganic oxygen compoundOrganooxygen compoundPolyolSecondary alcoholUnsaturated fatty acidSolidlogp4.61logs-3.90solubility4.41e-02 g/llogp3.05pka_strongest_acidic4.48pka_strongest_basic-1.6iupac(5S,6R,7E,9E,15S)-5,6,15-trihydroxyicosa-7,9,11,13-tetraenoic acidaverage_mass352.4651mono_mass352.224974134smiles[H][C@](O)(CCCCC)C=CC=C\C=C\C=C\[C@@]([H])(O)[C@@]([H])(O)CCCC(O)=OformulaC20H32O5inchiInChI=1S/C20H32O5/c1-2-3-8-12-17(21)13-9-6-4-5-7-10-14-18(22)19(23)15-11-16-20(24)25/h4-7,9-10,13-14,17-19,21-23H,2-3,8,11-12,15-16H2,1H3,(H,24,25)/b6-4?,7-5+,13-9?,14-10+/t17-,18+,19-/m0/s1inchikeyIXAQOQZEOGMIQS-WZCAPKNJSA-Npolar_surface_area97.99refractivity104.35polarizability42.15rotatable_bond_count14acceptor_count5donor_count4physiological_charge-1formal_charge0HMDB043856498#<Reference:0x0000555674972b68>#<Reference:0x0000555674972848>#<Reference:0x0000555674972370>#<Reference:0x00005556749721b8>#<Reference:0x0000555674972000>#<Reference:0x0000555674971e48>#<Reference:0x0000555674971c90>#<Reference:0x0000555674971ad8>#<Reference:0x0000555674971830>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