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Record Information
Version5.0
StatusDetected and Quantified
Creation Date2006-08-13 17:34:02 UTC
Update Date2021-09-14 15:46:28 UTC
HMDB IDHMDB0004362
Secondary Accession Numbers
  • HMDB04362
Metabolite Identification
Common Name4-Hydroxynonenal
Description4-Hydroxynonenal (HNE), one of the major end products of lipid peroxidation, has been shown to be involved in signal transduction and available evidence suggests that it can affect cell cycle events in a concentration-dependent manner. glutathione S-transferases (GSTs) can modulate the intracellular concentrations of HNE by affecting its generation during lipid peroxidation by reducing hydroperoxides and also by converting it into a glutathione conjugate. Overexpression of the Alpha class GSTs in cells leads to lower steady-state levels of HNE, and these cells acquire resistance to apoptosis induced by lipid peroxidation-causing agents such as H(2)O(2), UVA, superoxide anion, and pro-oxidant xenobiotics, suggesting that signaling for apoptosis by these agents is transduced through HNE. Cells with the capacity to exclude HNE from the intracellular environment at a faster rate are relatively more resistant to apoptosis caused by H(2)O(2), UVA, superoxide anion, and pro-oxidant xenobiotics as well as by HNE, suggesting that HNE may be a common denominator in mechanisms of apoptosis caused by oxidative stress. Transfection of adherent cells with HNE-metabolizing GSTs leads to transformation of these cells due to depletion of HNE. (PMID 15288119 ). HNE has also been identified as a uremic toxin according to the European Uremic Toxin Working Group (PMID: 22626821 ).
Structure
Data?1582752306
Synonyms
ValueSource
(e)-4-Hydroxy-2-nonenalChEBI
4-Hydroxy-2,3-trans-nonenalChEBI
HNEChEBI
trans-4-Hydroxy-2-nonenalChEBI
4-Hydroxy-2,3-nonenalHMDB
4-Hydroxy-2-nonenalHMDB
4-Hydroxynon-2-enalHMDB
4-Hydroxynonen-2-alHMDB
4-HNE CPDHMDB
4-Hydroxy-2-nonenal, (e)-isomerHMDB
4-HydroxynonenalChEBI
Chemical FormulaC9H16O2
Average Molecular Weight156.2221
Monoisotopic Molecular Weight156.115029756
IUPAC Name(2E)-4-hydroxynon-2-enal
Traditional Nametrans-4-hydroxy-2-nonenal
CAS Registry Number75899-68-2
SMILES
CCCCCC(O)\C=C\C=O
InChI Identifier
InChI=1S/C9H16O2/c1-2-3-4-6-9(11)7-5-8-10/h5,7-9,11H,2-4,6H2,1H3/b7-5+
InChI KeyJVJFIQYAHPMBBX-FNORWQNLSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as fatty alcohols. These are aliphatic alcohols consisting of a chain of a least six carbon atoms.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty alcohols
Direct ParentFatty alcohols
Alternative Parents
Substituents
  • Fatty alcohol
  • Medium-chain aldehyde
  • Enal
  • Alpha,beta-unsaturated aldehyde
  • Secondary alcohol
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aldehyde
  • Alcohol
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Industrial application:

Biological role:

Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility3.08 g/LALOGPS
logP1.87ALOGPS
logP1.75ChemAxon
logS-1.7ALOGPS
pKa (Strongest Acidic)14.86ChemAxon
pKa (Strongest Basic)-2.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity46.56 m³·mol⁻¹ChemAxon
Polarizability18.71 ųChemAxon
Number of Rings0ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted Spectral Properties

Collision Cross Sections

NameAdductTypeData SourceValueReference
DarkChem[M+H]+PredictedNot Available139.5131661259
DarkChem[M-H]-PredictedNot Available136.1631661259

Retention Indices

Underivatized

Not Available

Derivatized

DerivativeValueReference
4-Hydroxynonenal,1TMS,#11432.4922https://arxiv.org/abs/1905.12712
4-Hydroxynonenal,1TBDMS,#11668.1843https://arxiv.org/abs/1905.12712
Spectra

GC-MS

Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4r-9000000000-2b2e86f0d26bfcdbaa7c2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0a4i-9800000000-f25e4e5c5bfdea54d97c2017-10-06View Spectrum
MSMass Spectrum (Electron Ionization)splash10-0a4r-9000000000-2b2e86f0d26bfcdbaa7c2021-09-05View Spectrum

LC-MS/MS

Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-052r-1900000000-9e0485f40ddea525bfb22016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0abi-9700000000-14b48d43b52506ea875a2016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4l-9000000000-c60e1ce771da41f3cef12016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-1900000000-963698def33862d38ed82016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-3900000000-39790f81d0ebc18f6f712016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9100000000-a4ef5b05613d7c9115282016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0900000000-c09fa78f1a3efa8c0e312021-09-06View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0ab9-5900000000-5f46d902d1ecb2e14a932021-09-06View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0aor-9100000000-e66e02441083fb8392a52021-09-06View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0007-9300000000-9c3d48d2b69a51fb7d632021-09-07View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00r6-9000000000-fdc847c35b84e0c9d8942021-09-07View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-d7140511cfc2bca207a82021-09-07View Spectrum
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Feces
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.11 +/- 0.06 uMAdult (>18 years old)BothNormal details
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot Available
Normal
      Not Available
details
Cerebrospinal Fluid (CSF)Detected and Quantified0.38 (0.24-0.52) uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified1.3 +/- 0.2 uMElderly (>65 years old)BothNormal details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified0.00028 +/- 0.000079 umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified2650.0 +/- 140.0 uMAdult (>18 years old)BothPeripheral arterial disease details
BloodDetected and Quantified0.75 +/- 0.31 uMAdult (>18 years old)Bothuremia details
Cerebrospinal Fluid (CSF)Detected and Quantified1.47 (0.71-2.23) uMAdult (>18 years old)Not SpecifiedParkinson's disease details
Cerebrospinal Fluid (CSF)Detected and Quantified0.40 +/- 0.030 uMAdult (>18 years old)Not SpecifiedAlzheimer's disease details
Cerebrospinal Fluid (CSF)Detected and Quantified0.36 +/- 0.03 uMAdult (>18 years old)BothAlzheimer's disease details
FecesDetected but not QuantifiedNot QuantifiedAdult (>18 years old)Both
Colorectal cancer
details
Associated Disorders and Diseases
Disease References
Peripheral vascular disease
  1. Signorelli SS, Fatuzzo P, Rapisarda F, Neri S, Ferrante M, Oliveri Conti G, Fallico R, Di Pino L, Pennisi G, Celotta G, Massimiliano A: A randomised, controlled clinical trial evaluating changes in therapeutic efficacy and oxidative parameters after treatment with propionyl L-carnitine in patients with peripheral arterial disease requiring haemodialysis. Drugs Aging. 2006;23(3):263-70. [PubMed:16608381 ]
Uremia
  1. Duranton F, Cohen G, De Smet R, Rodriguez M, Jankowski J, Vanholder R, Argiles A: Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol. 2012 Jul;23(7):1258-70. doi: 10.1681/ASN.2011121175. Epub 2012 May 24. [PubMed:22626821 ]
Parkinson's disease
  1. Selley ML: (E)-4-hydroxy-2-nonenal may be involved in the pathogenesis of Parkinson's disease. Free Radic Biol Med. 1998 Jul 15;25(2):169-74. [PubMed:9667492 ]
Alzheimer's disease
  1. Selley ML, Close DR, Stern SE: The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer's disease. Neurobiol Aging. 2002 May-Jun;23(3):383-8. [PubMed:11959400 ]
Colorectal cancer
  1. Goedert JJ, Sampson JN, Moore SC, Xiao Q, Xiong X, Hayes RB, Ahn J, Shi J, Sinha R: Fecal metabolomics: assay performance and association with colorectal cancer. Carcinogenesis. 2014 Sep;35(9):2089-96. doi: 10.1093/carcin/bgu131. Epub 2014 Jul 18. [PubMed:25037050 ]
Associated OMIM IDs
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDFDB020986
KNApSAcK IDC00000447
Chemspider ID4446465
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia Link4-Hydroxynonenal
METLIN IDNot Available
PubChem Compound5283344
PDB IDNot Available
ChEBI ID58968
Food Biomarker OntologyNot Available
VMH IDCE2006
MarkerDB IDMDB00000448
References
Synthesis ReferenceEsterbauer, Hermann; Benedetti, Angelo; Lang, Johanna; Fulceri, Rosella; Fauler, Gunther; Comporti, Mario. Studies on the mechanism of formation of 4-hydroxynonenal during microsomal lipid peroxidation. Biochimica et Biophysica Acta, Lipids and Lipid Metabolism (1986), 876(1), 154-66.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Selley ML, Close DR, Stern SE: The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer's disease. Neurobiol Aging. 2002 May-Jun;23(3):383-8. [PubMed:11959400 ]
  2. Selley ML: (E)-4-hydroxy-2-nonenal may be involved in the pathogenesis of Parkinson's disease. Free Radic Biol Med. 1998 Jul 15;25(2):169-74. [PubMed:9667492 ]
  3. Awasthi YC, Yang Y, Tiwari NK, Patrick B, Sharma A, Li J, Awasthi S: Regulation of 4-hydroxynonenal-mediated signaling by glutathione S-transferases. Free Radic Biol Med. 2004 Sep 1;37(5):607-19. [PubMed:15288119 ]
  4. Duranton F, Cohen G, De Smet R, Rodriguez M, Jankowski J, Vanholder R, Argiles A: Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol. 2012 Jul;23(7):1258-70. doi: 10.1681/ASN.2011121175. Epub 2012 May 24. [PubMed:22626821 ]

Enzymes

General function:
Involved in glutathione transferase activity
Specific function:
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. This isozyme has a high catalytic efficiency with 4-hydroxyalkenals such as 4-hydroxynonenal (4-HNE).
Gene Name:
GSTA4
Uniprot ID:
O15217
Molecular weight:
25703.905
References
  1. Awasthi YC, Yang Y, Tiwari NK, Patrick B, Sharma A, Li J, Awasthi S: Regulation of 4-hydroxynonenal-mediated signaling by glutathione S-transferases. Free Radic Biol Med. 2004 Sep 1;37(5):607-19. [PubMed:15288119 ]