ContaminantDB: 4-Hydroxynonenal

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (16)XML

Record Information

Version

1.0

Creation Date

2014-08-29 05:50:23 UTC

Update Date

2026-04-06 12:00:38 UTC

Accession Number

CHEM003140

Identification

Common Name

4-Hydroxynonenal

Class

Small Molecule

Description

4-Hydroxynonenal is a uremic toxin. Uremic toxins can be subdivided into three major groups based upon their chemical and physical characteristics: 1) small, water-soluble, non-protein-bound compounds, such as urea; 2) small, lipid-soluble and/or protein-bound compounds, such as the phenols and 3) larger so-called middle-molecules, such as beta2-microglobulin. Chronic exposure of uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease. 4-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. (2).

Contaminant Sources

FooDB Chemicals
HMDB Contaminants - Urine
T3DB toxins
ToxCast & Tox21 Chemicals

Contaminant Type

Ester
Food Toxin
Metabolite
Natural Compound
Organic Compound
Uremic Toxin

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
(e)-4-Hydroxy-2-nonenal	ChEBI
4-Hydroxy-2,3-trans-nonenal	ChEBI
HNE	ChEBI
trans-4-Hydroxy-2-nonenal	ChEBI
4-Hydroxy-2,3-nonenal	HMDB
4-Hydroxy-2-nonenal	HMDB
4-Hydroxynon-2-enal	HMDB
4-Hydroxynonen-2-al	HMDB
4-HNE CPD	HMDB
4-Hydroxy-2-nonenal, (e)-isomer	HMDB
4-Hydroxynonenal	ChEBI

Chemical Formula

C₉H₁₆O₂

Average Molecular Mass

156.222 g/mol

Monoisotopic Mass

156.115 g/mol

CAS Registry Number

75899-68-2

IUPAC Name

(2E)-4-hydroxynon-2-enal

Traditional Name

trans-4-hydroxy-2-nonenal

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 Key

JVJFIQYAHPMBBX-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.

Kingdom

Organic compounds

Super Class

Lipids and lipid-like molecules

Class

Fatty Acyls

Sub Class

Fatty alcohols

Direct Parent

Fatty 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 Framework

Aliphatic acyclic compounds

External Descriptors

4-hydroxynon-2-enal (CHEBI:58968 )
Fatty aldehydes (LMFA06000051 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	Not Available
Boiling Point	Not Available
Solubility	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	3.08 g/L	ALOGPS
logP	1.87	ALOGPS
logP	1.75	ChemAxon
logS	-1.7	ALOGPS
pKa (Strongest Acidic)	14.86	ChemAxon
pKa (Strongest Basic)	-2.9	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	37.3 Å²	ChemAxon
Rotatable Bond Count	6	ChemAxon
Refractivity	46.56 m³·mol⁻¹	ChemAxon
Polarizability	18.71 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a4r-9000000000-2b2e86f0d26bfcdbaa7c	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-0a4i-9800000000-f25e4e5c5bfdea54d97c	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-052r-1900000000-9e0485f40ddea525bfb2	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0abi-9700000000-14b48d43b52506ea875a	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4l-9000000000-c60e1ce771da41f3cef1	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-1900000000-963698def33862d38ed8	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0a4i-3900000000-39790f81d0ebc18f6f71	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9100000000-a4ef5b05613d7c911528	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-03di-0900000000-c09fa78f1a3efa8c0e31	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0ab9-5900000000-5f46d902d1ecb2e14a93	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0aor-9100000000-e66e02441083fb8392a5	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0007-9300000000-9c3d48d2b69a51fb7d63	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00r6-9000000000-fdc847c35b84e0c9d894	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9000000000-d7140511cfc2bca207a8	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
1D NMR	13C NMR Spectrum	Not Available	Spectrum

Toxicity Profile

Route of Exposure

Endogenous, Ingestion, Dermal (contact)

Mechanism of Toxicity

Uremic toxins such as 4-Hydroxynonenal are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (4). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (5).

Metabolism

Uremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Naturally produced by the body (endogenous).

Minimum Risk Level

Not Available

Health Effects

Chronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.

Symptoms

As a uremic toxin, this compound can cause uremic syndrome. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur. Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome. Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present.

Treatment

Kidney dialysis is usually needed to relieve the symptoms of uremic syndrome until normal kidney function can be restored.

Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

HMDB0004362

FooDB ID

FDB020986

Phenol Explorer ID

Not Available

KNApSAcK ID

C00000447

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

Not Available

PDB ID

Not Available

Wikipedia Link

Chemspider ID

ChEBI ID

PubChem Compound ID

Kegg Compound ID

Not Available

YMDB ID

Not Available

ECMDB ID

Not Available

References

Synthesis Reference

Esterbauer, 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.

MSDS

Not Available

General References

1. Esterbauer, 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. https://www.ncbi.nlm.nih.gov/pubmed/?term=16603628

7. https://www.ncbi.nlm.nih.gov/pubmed/?term=17189262

8. https://www.ncbi.nlm.nih.gov/pubmed/?term=23543734

9. https://www.ncbi.nlm.nih.gov/pubmed/?term=26800898

4-Hydroxynonenal (CHEM003140)

Structure for CHEM003140: 4-Hydroxynonenal