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Record Information
Version3.6
Creation Date2006-08-14 00:30:47 UTC
Update Date2013-05-29 19:40:47 UTC
HMDB IDHMDB04688
Secondary Accession NumbersNone
Metabolite Identification
Common NameHepoxilin A3
DescriptionHepoxilin A3 is an electrophilic eicosanoids synthesized during arachidonic acid oxidative metabolism, which can participate in the Michael addition reaction with glutathione (GSH, a major cellular antioxidant) catalyzed by the GSH-S-transferase (GST) family. GSH-adducts have been observed with molecules synthesized through the 12-lipoxygenase pathway. (PMID 12432937 ). Hepoxilins have biological actions that appear to have, as their basis, changes in intracellular concentrations of ions including calcium and potassium ions as well as changes in second messenger systems. Recent evidence suggests that the biological actions of the hepoxilins may be receptor-mediated as indicated from data showing the existence of hepoxilin-specific binding proteins in the human neutrophils. Such evidence also implicates the association of G-proteins both in hepoxilin-binding as well as in hepoxilin action. (PMID 7947989 ).
Structure
Thumb
Synonyms
  1. (5Z,9E)-8-hydroxy-10-{(2S,3S)-3-[(2Z)-oct-2-en-1-yl]oxiran-2-yl}deca-5,9-dienoate
  2. (5Z,9E)-8-hydroxy-10-{(2S,3S)-3-[(2Z)-oct-2-en-1-yl]oxiran-2-yl}deca-5,9-dienoic acid
  3. (5Z,9E,14Z)-(11S,12S)-11,12-Epoxy-8-hydroxyeicosa-5,9,14-trienoate
  4. (5Z,9E,14Z)-(11S,12S)-11,12-Epoxy-8-hydroxyeicosa-5,9,14-trienoic acid
  5. (5Z,9E,14Z)-(11S,12S)-11,12-Epoxy-8-hydroxyicosa-5,9,14-trienoate
  6. (5Z,9E,14Z)-(11S,12S)-11,12-Epoxy-8-hydroxyicosa-5,9,14-trienoic acid
  7. 8-Hydroxy-11,12-epoxyeicosa-5,9,14-trienoate
  8. 8-Hydroxy-11,12-epoxyeicosa-5,9,14-trienoic acid
  9. 8-Hydroxy-11S,12S-epoxy-5Z,14Z,9E-eicosatrienoate
  10. 8-Hydroxy-11S,12S-epoxy-5Z,14Z,9E-eicosatrienoic acid
Chemical FormulaC20H32O4
Average Molecular Weight336.4657
Monoisotopic Molecular Weight336.230059512
IUPAC Name(5Z,9E)-8-hydroxy-10-[(2R,3S)-3-[(2Z)-oct-2-en-1-yl]oxiran-2-yl]deca-5,9-dienoic acid
Traditional IUPAC Name(5Z,9E)-8-hydroxy-10-[(2R,3S)-3-[(2Z)-oct-2-en-1-yl]oxiran-2-yl]deca-5,9-dienoic acid
CAS Registry Number85589-24-8
SMILES
CCCCC\C=C/C[C@@H]1O[C@@H]1\C=C\C(O)C\C=C/CCCC(O)=O
InChI Identifier
InChI=1S/C20H32O4/c1-2-3-4-5-6-10-13-18-19(24-18)16-15-17(21)12-9-7-8-11-14-20(22)23/h6-7,9-10,15-19,21H,2-5,8,11-14H2,1H3,(H,22,23)/b9-7-,10-6-,16-15+/t17?,18-,19+/m0/s1
InChI KeySGTUOBURCVMACZ-CIQDQOFUSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassLipids
ClassEicosanoids
Sub ClassHepoxilins
Other Descriptors
  • Aliphatic Heteromonocyclic Compounds
  • Epoxy Fatty Acids
  • Organic Compounds
  • Unsaturated Fatty Acids
Substituents
  • Allyl Alcohol
  • Carboxylic Acid
  • Dialkyl Ether
  • Oxirane
  • Secondary Alcohol
Direct ParentHepoxilins
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
  • Food
Biofunction
  • Cell signaling
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability
Application
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Extracellular
  • Membrane (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
water solubility0.0094 g/LALOGPS
logP5.57ALOGPS
logP4.57ChemAxon
logS-4.6ALOGPS
pKa (strongest acidic)4.68ChemAxon
pKa (strongest basic)-2.9ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count2ChemAxon
polar surface area70.06ChemAxon
rotatable bond count14ChemAxon
refractivity99.72ChemAxon
polarizability38.57ChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
Tissue Location
  • Epidermis
  • Neutrophil
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.114 +/- 0.087 uMAdult (>18 years old)Not Specified
Normal
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB023406
KNApSAcK IDNot Available
Chemspider ID4573947
KEGG Compound IDC14808
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
NuGOwiki LinkHMDB04688
Metagene LinkHMDB04688
METLIN ID7070
PubChem Compound5460414
PDB IDNot Available
ChEBI ID15631
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Savidge TC, Newman PG, Pan WH, Weng MQ, Shi HN, McCormick BA, Quaroni A, Walker WA: Lipopolysaccharide-induced human enterocyte tolerance to cytokine-mediated interleukin-8 production may occur independently of TLR-4/MD-2 signaling. Pediatr Res. 2006 Jan;59(1):89-95. Epub 2005 Dec 2. Pubmed: 16326999
  2. Sutherland M, Schewe T, Nigam S: Biological actions of the free acid of hepoxilin A3 on human neutrophils. Biochem Pharmacol. 2000 Feb 15;59(4):435-40. Pubmed: 10644052
  3. Demin PM, Reynaud D, Pace-Asciak CR: Chemical synthesis and actions of 11,12-thiirano-hepoxilin A3. J Lipid Mediat Cell Signal. 1996 Jan;13(1):63-72. Pubmed: 8998598
  4. Murphy RC, Zarini S: Glutathione adducts of oxyeicosanoids. Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:471-82. Pubmed: 12432937
  5. Mills L, Reynaud D, Pace-Asciak CR: Hepoxilin-evoked intracellular reorganization of calcium in human neutrophils: a confocal microscopy study. Exp Cell Res. 1997 Feb 1;230(2):337-41. Pubmed: 9024792
  6. Pace-Asciak CR, Reynaud D, Laneuville O, Grinstein S, Nigam S: Hepoxilin A3 inhibits agonist-evoked rise in free intracellular calcium in human neutrophils. Adv Exp Med Biol. 1997;400A:375-80. Pubmed: 9547579
  7. Mrsny RJ, Gewirtz AT, Siccardi D, Savidge T, Hurley BP, Madara JL, McCormick BA: Identification of hepoxilin A3 in inflammatory events: a required role in neutrophil migration across intestinal epithelia. Proc Natl Acad Sci U S A. 2004 May 11;101(19):7421-6. Epub 2004 May 3. Pubmed: 15123795
  8. Nigam S, Patabhiraman S, Ciccoli R, Ishdorj G, Schwarz K, Petrucev B, Kuhn H, Haeggstrom JZ: The rat leukocyte-type 12-lipoxygenase exhibits an intrinsic hepoxilin A3 synthase activity. J Biol Chem. 2004 Jul 9;279(28):29023-30. Epub 2004 May 3. Pubmed: 15123652
  9. Reynaud D, Demin PM, Sutherland M, Nigam S, Pace-Asciak CR: Hepoxilin signaling in intact human neutrophils: biphasic elevation of intracellular calcium by unesterified hepoxilin A3. FEBS Lett. 1999 Mar 12;446(2-3):236-8. Pubmed: 10100848
  10. Yu Z, Schneider C, Boeglin WE, Marnett LJ, Brash AR: The lipoxygenase gene ALOXE3 implicated in skin differentiation encodes a hydroperoxide isomerase. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9162-7. Epub 2003 Jul 24. Pubmed: 12881489
  11. Anton R, Puig L, Esgleyes T, de Moragas JM, Vila L: Occurrence of hepoxilins and trioxilins in psoriatic lesions. J Invest Dermatol. 1998 Apr;110(4):303-10. Pubmed: 9540966
  12. Pace-Asciak CR, Reynaud D, Rounova O, Demin P, Pivnitsky KK: Hepoxilin A3 is metabolized into its omega-hydroxy metabolite by human neutrophils. Adv Exp Med Biol. 1999;469:535-8. Pubmed: 10667379
  13. Dho S, Grinstein S, Corey EJ, Su WG, Pace-Asciak CR: Hepoxilin A3 induces changes in cytosolic calcium, intracellular pH and membrane potential in human neutrophils. Biochem J. 1990 Feb 15;266(1):63-8. Pubmed: 2106877
  14. Hurley BP, Siccardi D, Mrsny RJ, McCormick BA: Polymorphonuclear cell transmigration induced by Pseudomonas aeruginosa requires the eicosanoid hepoxilin A3. J Immunol. 2004 Nov 1;173(9):5712-20. Pubmed: 15494523
  15. Nigam S, Nodes S, Cichon G, Corey EJ, Pace-Asciak CR: Receptor-mediated action of hepoxilin A3 releases diacylglycerol and arachidonic acid from human neutrophils. Biochem Biophys Res Commun. 1990 Sep 28;171(3):944-8. Pubmed: 2171511
  16. Reynaud D, Rounova O, Demin PM, Pivnitsky KK, Pace-Asciak CR: Hepoxilin A3 is oxidized by human neutrophils into its omega-hydroxy metabolite by an activity independent of LTB4 omega-hydroxylase. Biochim Biophys Acta. 1997 Oct 18;1348(3):287-98. Pubmed: 9366245
  17. Pace-Asciak CR: Hepoxilins: a review on their cellular actions. Biochim Biophys Acta. 1994 Nov 17;1215(1-2):1-8. Pubmed: 7947989