Human Metabolome Database Version 3.5

Showing metabocard for Hepoxilin A3 (HMDB04688)

Record Information
Version 3.5
Creation Date 2006-08-13 18:30:47 -0600
Update Date 2013-05-29 13:40:47 -0600
Secondary Accession Numbers None
Metabolite Identification
Common Name Hepoxilin A3
Description Hepoxilin 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 Link_out). 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 Link_out).
Structure Thumb
Download: MOL | SDF | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
  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 Formula C20H32O4
Average Molecular Weight 336.4657
Monoisotopic Molecular Weight 336.230059512
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 Number 85589-24-8
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
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Lipids
Class Eicosanoids
Sub Class Hepoxilins
Other Descriptors
  • Aliphatic Heteromonocyclic Compounds
  • Epoxy Fatty Acids
  • Organic Compounds
  • Unsaturated Fatty Acids
  • Allyl Alcohol
  • Carboxylic Acid
  • Dialkyl Ether
  • Oxirane
  • Secondary Alcohol
Direct Parent Hepoxilins
Status Detected and Quantified
  • Endogenous
  • Food
  • Cell signaling
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Extracellular
  • Membrane (predicted from logP)
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point Not Available Not Available
Boiling Point Not Available Not Available
Water Solubility Not Available Not Available
LogP Not Available Not Available
Predicted Properties
Property Value Source
Water Solubility 0.0094 g/L ALOGPS
LogP 5.57 ALOGPS
LogP 4.57 ChemAxon
LogS -4.56 ALOGPS
pKa (strongest acidic) 4.68 ChemAxon
pKa (strongest basic) -2.9 ChemAxon
Hydrogen Acceptor Count 4 ChemAxon
Hydrogen Donor Count 2 ChemAxon
Polar Surface Area 70.06 A2 ChemAxon
Rotatable Bond Count 14 ChemAxon
Refractivity 99.72 ChemAxon
Polarizability 38.57 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge -1 ChemAxon
Not Available
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
Tissue Location
  • Epidermis
  • Neutrophil
Pathways Not Available
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified
0.114 +/- 0.087 uM Adult (>18 years old) Not Specified Comment Normal
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease References None
Associated OMIM IDs None
DrugBank ID Not Available
DrugBank Metabolite ID Not Available
Phenol Explorer Compound ID Not Available
Phenol Explorer Metabolite ID Not Available
FoodDB ID FDB023406
KNApSAcK ID Not Available
Chemspider ID 4573947 Link_out
KEGG Compound ID C14808 Link_out
BioCyc ID Not Available
BiGG ID Not Available
Wikipedia Link Not Available
NuGOwiki Link HMDB04688 Link_out
Metagene Link HMDB04688 Link_out
METLIN ID 7070 Link_out
PubChem Compound 5460414 Link_out
PDB ID Not Available
ChEBI ID 15631 Link_out
Synthesis Reference Not 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 Link_out
  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 Link_out
  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 Link_out
  4. Murphy RC, Zarini S: Glutathione adducts of oxyeicosanoids. Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:471-82. Pubmed: 12432937 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out
  17. Pace-Asciak CR: Hepoxilins: a review on their cellular actions. Biochim Biophys Acta. 1994 Nov 17;1215(1-2):1-8. Pubmed: 7947989 Link_out