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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2006-05-22 14:17:45 UTC
Update Date2017-12-07 01:48:42 UTC
HMDB IDHMDB0002265
Secondary Accession Numbers
  • HMDB02265
  • HMDB02342
Metabolite Identification
Common Name14,15-DiHETrE
Description14,15-DiHETrE is a Cytochrome P450 (P450) eicosanoid. Eicosanoids generated from arachidonic acid metabolism by cytochrome P450 (P450) enzymes are important autocrine and paracrine factors that have diverse biological functions. P450 eicosanoids are involved in the regulation of vascular tone, renal tubular transport, cardiac contractility, cellular proliferation, and inflammation. Regulation of P450 eicosanoid levels is determined by many factors, including the induction or repression of the P450 enzymes responsible for their formation. Fibrate drugs are part of a diverse group of compounds known as peroxisome proliferators, which also include herbicides and phthalate ester plasticizers. Peroxisome proliferators act via peroxisome proliferator-activated receptor (PPAR ). This receptor is a member of the PPAR nuclear receptor family that also consists of the PPAR and PPAR isoforms. PPAR is mainly expressed in the heart, liver, and kidney, whereas the expression of PPAR is predominantly in the adipose tissue. The biological role of PPAR as a lipid sensor has been well established. 14,15-DiHETrE is a potent activators of PPAR and PPAR, shown to induce the binding of PPAR to a peroxisome proliferator response element (PPRE). Furthermore, 14,15-DiHETrE behaves like peroxisome proliferators in that is able to alter apoA-I and apoA-II mRNA expression. 14,15-DiHETrE is the most potent PPARalpha activator in a COS-7 cell expression system producing a 12-fold increase in PPARalpha-mediated luciferase activity. (PMID: 17431031 , 16113065 ).
Structure
Thumb
Synonyms
ValueSource
(+/-)14,15-dihetreChEBI
(5Z,8Z,11Z)-14,15-Dihydroxyeicosa-5,8,11-trienoic acidChEBI
(5Z,8Z,11Z)-14,15-Dihydroxyicosa-5,8,11-trienoic acidChEBI
14,15-Dihydroxy-5Z,8Z,11Z-eicosatrienoic acidChEBI
14,15-Dihydroxyeicosatrienoic acidChEBI
(5Z,8Z,11Z)-14,15-Dihydroxyeicosa-5,8,11-trienoateGenerator
(5Z,8Z,11Z)-14,15-Dihydroxyicosa-5,8,11-trienoateGenerator
14,15-Dihydroxy-5Z,8Z,11Z-eicosatrienoateGenerator
14,15-DihydroxyeicosatrienoateGenerator
14,15-DHETHMDB
Chemical FormulaC20H34O4
Average Molecular Weight338.4816
Monoisotopic Molecular Weight338.245709576
IUPAC Name(5Z,8Z,11Z)-14,15-dihydroxyicosa-5,8,11-trienoic acid
Traditional Name14,15-DiHETrE
CAS Registry Number77667-09-5
SMILES
CCCCCC(O)C(O)C\C=C/C\C=C/C\C=C/CCCC(O)=O
InChI Identifier
InChI=1S/C20H34O4/c1-2-3-12-15-18(21)19(22)16-13-10-8-6-4-5-7-9-11-14-17-20(23)24/h4,6-7,9-10,13,18-19,21-22H,2-3,5,8,11-12,14-17H2,1H3,(H,23,24)/b6-4-,9-7-,13-10-
InChI KeySYAWGTIVOGUZMM-ILYOTBPNSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as hydroxyeicosatrienoic acids. These are eicosanoic acids with an attached hydroxyl group and three CC double bonds.
KingdomChemical entities
Super ClassOrganic compounds
ClassLipids and lipid-like molecules
Sub ClassFatty Acyls
Direct ParentHydroxyeicosatrienoic acids
Alternative Parents
Substituents
  • Hydroxyeicosatrienoic acid
  • Long-chain fatty acid
  • Hydroxy fatty acid
  • Unsaturated fatty acid
  • Fatty acid
  • Secondary alcohol
  • 1,2-diol
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organic oxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

  Cell and elements:

Source:

  Biological:

    Animal:

Route of exposure:

  Enteral:

Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

    Cellular process:

    Chemical reaction:

    Biochemical process:

Role

Industrial application:

Biological role:

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 Solubility0.014 g/LALOGPS
logP5.28ALOGPS
logP4.49ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)4.82ChemAxon
pKa (Strongest Basic)-3.1ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area77.76 ŲChemAxon
Rotatable Bond Count15ChemAxon
Refractivity101.87 m³·mol⁻¹ChemAxon
Polarizability39.75 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-007c-7492000000-53d0c760eca4ea7c74b7View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positivesplash10-00a9-9222530000-2b02e3de22d55ff2a440View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0019000000-7f7f92b8b0190b675203View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-9554000000-c5755d9eb5a2aadcbe2cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0597-9410000000-125ce6f656a7b73f6d93View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0019000000-4e33cef8debb2f547534View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00kr-5498000000-73635b3c1d4840cbee34View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9340000000-922bf4ce3cb3318c6c5aView in MoNA
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
Tissue LocationNot Available
Pathways
NameSMPDB/PathwhizKEGG
Acetaminophen Action PathwayPw000687Pw000687 greyscalePw000687 simpleNot Available
Acetylsalicylic Acid PathwayPw000128Pw000128 greyscalePw000128 simpleNot Available
Antipyrine Action PathwayPw000669Pw000669 greyscalePw000669 simpleNot Available
Antrafenine Action PathwayPw000670Pw000670 greyscalePw000670 simpleNot Available
Arachidonic Acid MetabolismPw000044Pw000044 greyscalePw000044 simpleMap00590
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.001449 +/- 7.1E-5 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.000714 +/- 0.000031 uMAdult (>18 years old)Both
Normal
details
BloodDetected and Quantified0.00122 +/- 0.000705 uMAdult (>18 years old)Not SpecifiedNormal
    • Oxygenated lipids...
details
BloodDetected and Quantified0.000603 +/- 0.00018 uMAdult (>18 years old)Both
Normal
details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00013 +/- 0.00006 uMAdult (>18 years old)Both
Normal
    • John W. Newman, U...
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 IDFDB022935
KNApSAcK IDNot Available
Chemspider ID4446271
KEGG Compound IDC14775
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN IDNot Available
PubChem Compound5283147
PDB IDNot Available
ChEBI ID63966
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Ng VY, Huang Y, Reddy LM, Falck JR, Lin ET, Kroetz DL: Cytochrome P450 eicosanoids are activators of peroxisome proliferator-activated receptor alpha. Drug Metab Dispos. 2007 Jul;35(7):1126-34. Epub 2007 Apr 12. [PubMed:17431031 ]
  2. Fang X, Hu S, Xu B, Snyder GD, Harmon S, Yao J, Liu Y, Sangras B, Falck JR, Weintraub NL, Spector AA: 14,15-Dihydroxyeicosatrienoic acid activates peroxisome proliferator-activated receptor-alpha. Am J Physiol Heart Circ Physiol. 2006 Jan;290(1):H55-63. Epub 2005 Aug 19. [PubMed:16113065 ]

Enzymes

General function:
Involved in catalytic activity
Specific function:
Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides. Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid, 12-phosphonooxy-octadec-9E-enoic acid, and p-nitrophenyl phospate.
Gene Name:
EPHX2
Uniprot ID:
P34913
Molecular weight:
62615.22
Reactions
14,15-Epoxy-5,8,11-eicosatrienoic acid + Water → 14,15-DiHETrEdetails