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Record Information
Version2.0
Creation Date2009-03-06 18:57:58 UTC
Update Date2014-12-24 20:20:56 UTC
Accession NumberT3D0037
Identification
Common NameAcrolein
ClassSmall Molecule
DescriptionAcrolein (systematic name: propenal) is the simplest unsaturated aldehyde. It is a colourless liquid with a piercing, disagreeable, acrid smell. The smell of burnt fat (as when cooking oil is heated to its smoke point) is caused by glycerol in the burning fat breaking down into acrolein. It is produced industrially from propylene and mainly used as a biocide and a building block to other chemical compounds, such as the amino acid methionine. Acrolein is used as an etherification agent in the preparation of modified food starches. Acrolein is an herbicide and algicide used in water treatment. It is produced by microorganisms, e.g. Clostridium perfringens. Acrolein is a relatively electrophilic compound and a reactive one, hence its high toxicity. It is a good Michael acceptor, hence its useful reaction with thiols. It forms acetals readily, a prominent one being the spirocycle derived from pentaerythritol, diallylidene pentaerythritol. Acrolein participates in many Diels-Alder reactions, even with itself. Via Diels-Alder reactions, it is a precursor to some commercial fragrances, including lyral, norbornene-2-carboxaldehyde, and myrac aldehyde. Acrolein is toxic and is a strong irritant for the skin, eyes, and nasal passages. The main metabolic pathway for acrolein is the alkylation of glutathione. The WHO suggests a 'tolerable oral acrolein intake' of 7.5 mg/day per kilogram of body weight. Although acrolein occurs in French fries, the levels are only a few micrograms per kilogram.
Compound Type
  • Aldehyde
  • Food Toxin
  • Industrial Precursor/Intermediate
  • Industrial/Workplace Toxin
  • Lachrymator
  • Metabolite
  • Organic Compound
  • Pesticide
  • Pollutant
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
2-Propen-1-one
2-Propenal
2-Propenaldehyde
Acquinite
Acraldehyde
Acrylaldehyde
Acrylic Aldehyde
Aldehyde, acrylic
Allyl aldehyde
Aqualin
Aqualine
Biocide
CH2=CHCHO
Crolean
Ethylene aldehyde
Magnacide
Magnacide H
Papite
Prop-2-En-1-al
Prop-2-enal
Propenal
Propenaldehyde
Propylene aldehyde
Slimicide
trans-Acrolein Formylethylene
Chemical FormulaC3H4O
Average Molecular Mass56.063 g/mol
Monoisotopic Mass56.026 g/mol
CAS Registry Number107-02-8
IUPAC Nameprop-2-enal
Traditional Nameacrolein
SMILESC=CC=O
InChI IdentifierInChI=1S/C3H4O/c1-2-3-4/h2-3H,1H2
InChI KeyInChIKey=HGINCPLSRVDWNT-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as enals. These are an alpha,beta-unsaturated aldehyde of general formula RC=C-CH=O in which the aldehydic C=O function is conjugated to a C=C triple bond at the alpha,beta position.
KingdomOrganic compounds
Super ClassOrganic oxygen compounds
ClassOrganooxygen compounds
Sub ClassCarbonyl compounds
Direct ParentEnals
Alternative Parents
Substituents
  • Enal
  • Organic oxide
  • Hydrocarbon derivative
  • Short-chain aldehyde
  • Aldehyde
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Kidney
  • Liver
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceGreenish-yellow when impure
Experimental Properties
PropertyValue
Melting Point-87.7°C
Boiling Point52°C
Solubility212 mg/mL at 25°C
LogP-0.01
Predicted Properties
PropertyValueSource
Water Solubility107.0 mg/mLALOGPS
logP0.18ALOGPS
logP0.37ChemAxon
logS0.28ALOGPS
pKa (Strongest Basic)-4.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area17.07 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity16.37 m3·mol-1ChemAxon
Polarizability5.58 Å3ChemAxon
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-MSsplash10-0a6r-9000000000-4a086c1c9c7836b7b307View in MoNA
GC-MSGC-MS Spectrum - EI-Bsplash10-0a4i-9000000000-f6aba25388da7855f3ebView in MoNA
GC-MSGC-MS Spectrum - EI-Bsplash10-004i-9000000000-a667e77a9d666459b411View in MoNA
GC-MSGC-MS Spectrum - EI-Bsplash10-0a4i-9000000000-f6aba25388da7855f3ebView in MoNA
GC-MSGC-MS Spectrum - EI-Bsplash10-004i-9000000000-a667e77a9d666459b411View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-9000000000-cf50f66835baacbc5db4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-9000000000-abefe6f7a672744326c1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a6r-9000000000-32a4911454ef635f19edView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-9000000000-4740fe3b45257adba96aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-9000000000-e578c9fb2097eb472d12View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9000000000-c28d7e42ec75bd010f50View in MoNA
MSMass Spectrum (Electron Ionization)splash10-056r-9000000000-34c0891db414206d2b40View in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
Toxicity Profile
Route of ExposureOral (8) ; inhalation (8) ; dermal (8)
Mechanism of ToxicityAcrolein rapidly and irreversibly binds to lysine moieties and sulfhydryl groups found on many cellular molecules forming thiol ethers. By this mechanism acrolein can bind to messenger compounds to produce direct cytotoxic effects or secondary effects from interrupted cell signaling pathways. Perturbation of inflammatory responses in bronchial epithelial cells was demonstrated by direct action of acrolein on the inhibitor of nuclear factor kappa-B (IκB) kinase, which inhibits activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factor and suppresses interleukin 8 (IL-8) production. Rapid binding of acrolein to neural receptors in the corneal and nasal mucosa results in rapid depolarization of the associated neurons to produce ocular and nasal irritation. Acrolein also binds rapidly to glutathione, which may be inhibitory to the enzyme glutathione peroxidase and result in a lower level of cellular protection against oxygen radical toxicity. Further, the adduction of glutathione generates GS-propionaldehyde, which produces oxygen and possibly hydroxy radicals via cytosolic aldehyde dehydrogenase. Acrolein inhibits thioredoxin and thioredoxin reductase, which disrupts the cellular thiol redox balance necessary for cell survival. It interferes with normal reverse cholesterol transport by high density lipoprotein (HDL) by modifying specific sites in apolipoprotein A-I. Acrolein also inhibits aldehyde dehydrogenases and activates the transient receptor potential cation channel. (8, 1, 2, 3)
MetabolismAcrolein can be absorbed though oral, inhalation, or dermal routes. In the liver and kidneys, acrolein forms conjugates with glutathione, cysteine, N-acetylcysteine, and/or thioredoxin. Acrolein can also be transformed into acrylic acid by liver cytosol or microsomes, or it can be oxidized to glycidaldehyde by lung or liver microsomes. Acrolein metabolites are excreted in the urine. (8)
Toxicity ValuesLC50: 130 ppm over 30 minutes (Inhalation, Rat) (5) LD50: 562 mg/kg (Dermal, Rabbit) (6) LD50: 46 mg/kg (Oral, Rat) (6) LD50: 30 mg/kg (Subcutaneous, Rat) (6) High levels of acrolein (>7 mg/m3) cause injury to lungs after short term exposures.
Lethal Dose10 ppm for an adult human. (12)
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (11)
Uses/SourcesAcrolein is used as a pesticide to control algae, weeds, bacteria, and mollusks. It is also used to make other chemicals, such as polyester resin, polyurethane, propylene glycol, acrylic acid, acrylonitrile, and glycerol. Small amounts of acrolein can be formed when trees, tobacco, other plants, gasoline, and oil are burned. (8)
Minimum Risk LevelAcute Inhalation: 0.003 ppm (10) Intermediate Inhalation: 0.00004 ppm (10) Intermediate Oral: 2 mg/kg/day (10)
Health EffectsAcrolein is a severe pulmonary irritant and lachrymatory agent. Breathing large amounts of acrolein damages the lungs and could cause death. (8, 9)
SymptomsIngestion of acrolein causes stomach irritation, vomiting, stomach ulcers and bleeding. Breathing acrolein may cause eye watering, burning of the nose and throat and a decreased breathing rate. (8)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB41822
PubChem Compound ID7847
ChEMBL IDCHEMBL721
ChemSpider ID7559
KEGG IDC01471
UniProt IDNot Available
OMIM ID
ChEBI ID15368
BioCyc IDT-2-NONENAL-CMPD
CTD IDD000171
Stitch IDAcrolein
PDB IDNot Available
ACToR ID24
Wikipedia Linkacrolein
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Myers CR, Myers JM: The effects of acrolein on peroxiredoxins, thioredoxins, and thioredoxin reductase in human bronchial epithelial cells. Toxicology. 2009 Mar 4;257(1-2):95-104. doi: 10.1016/j.tox.2008.12.013. Epub 2008 Dec 24. [19135121 ]
  2. Bunting KD, Townsend AJ: Dependence of aldehyde dehydrogenase-mediated oxazaphosphorine resistance on soluble thiols: importance of thiol interactions with the secondary metabolite acrolein. Biochem Pharmacol. 1998 Jul 1;56(1):31-9. [9698086 ]
  3. Shao B, Fu X, McDonald TO, Green PS, Uchida K, O'Brien KD, Oram JF, Heinecke JW: Acrolein impairs ATP binding cassette transporter A1-dependent cholesterol export from cells through site-specific modification of apolipoprotein A-I. J Biol Chem. 2005 Oct 28;280(43):36386-96. Epub 2005 Aug 25. [16126721 ]
  4. Bautista DM, Jordt SE, Nikai T, Tsuruda PR, Read AJ, Poblete J, Yamoah EN, Basbaum AI, Julius D: TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell. 2006 Mar 24;124(6):1269-82. [16564016 ]
  5. Clayton GD and Clayton FE (eds) (1993-1994). Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc.
  6. ITII (1988). Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute.
  7. Marrs, Timothy T., Robert L. Maynard, and Frederick Sidell, eds. (2007). Chemical Warfare Agents: Toxicology and Treatment. 2nd edition. John Wiley & Sons. [ISBN: 978-0-470-01359-5]
  8. ATSDR - Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for acrolein. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  9. Wikipedia. Acrolein. Last Updated 14 April 2009. [Link]
  10. ATSDR - Agency for Toxic Substances and Disease Registry (2001). Minimal Risk Levels (MRLs) for Hazardous Substances. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  11. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  12. HSDB: Hazardous Substances Data Bank. National Library of Medicine (2001). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Retinal dehydrogenase activity
Specific Function:
Binds free retinal and cellular retinol-binding protein-bound retinal. Can convert/oxidize retinaldehyde to retinoic acid (By similarity).
Gene Name:
ALDH1A1
Uniprot ID:
P00352
Molecular Weight:
54861.44 Da
References
  1. Bunting KD, Townsend AJ: Dependence of aldehyde dehydrogenase-mediated oxazaphosphorine resistance on soluble thiols: importance of thiol interactions with the secondary metabolite acrolein. Biochem Pharmacol. 1998 Jul 1;56(1):31-9. [9698086 ]
  2. Yoval-Sanchez B, Rodriguez-Zavala JS: Differences in susceptibility to inactivation of human aldehyde dehydrogenases by lipid peroxidation byproducts. Chem Res Toxicol. 2012 Mar 19;25(3):722-9. doi: 10.1021/tx2005184. Epub 2012 Feb 29. [22339434 ]
General Function:
Temperature-gated cation channel activity
Specific Function:
Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
Gene Name:
TRPA1
Uniprot ID:
O75762
Molecular Weight:
127499.88 Da
References
  1. Takahashi N, Mizuno Y, Kozai D, Yamamoto S, Kiyonaka S, Shibata T, Uchida K, Mori Y: Molecular characterization of TRPA1 channel activation by cysteine-reactive inflammatory mediators. Channels (Austin). 2008 Jul-Aug;2(4):287-98. Epub 2008 Jul 6. [18769139 ]
  2. Nilius B, Prenen J, Owsianik G: Irritating channels: the case of TRPA1. J Physiol. 2011 Apr 1;589(Pt 7):1543-9. doi: 10.1113/jphysiol.2010.200717. Epub 2010 Nov 15. [21078588 ]
General Function:
Aldehyde dehydrogenase (nad) activity
Specific Function:
ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde. They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation.
Gene Name:
ALDH1B1
Uniprot ID:
P30837
Molecular Weight:
57205.93 Da
References
  1. Bunting KD, Townsend AJ: Dependence of aldehyde dehydrogenase-mediated oxazaphosphorine resistance on soluble thiols: importance of thiol interactions with the secondary metabolite acrolein. Biochem Pharmacol. 1998 Jul 1;56(1):31-9. [9698086 ]
General Function:
Thyroid hormone binding
Specific Function:
Recognizes as substrates free retinal and cellular retinol-binding protein-bound retinal. Seems to be the key enzyme in the formation of an RA gradient along the dorso-ventral axis during the early eye development and also in the development of the olfactory system (By similarity).
Gene Name:
ALDH1A3
Uniprot ID:
P47895
Molecular Weight:
56107.995 Da
References
  1. Bunting KD, Townsend AJ: Dependence of aldehyde dehydrogenase-mediated oxazaphosphorine resistance on soluble thiols: importance of thiol interactions with the secondary metabolite acrolein. Biochem Pharmacol. 1998 Jul 1;56(1):31-9. [9698086 ]
General Function:
Aldehyde dehydrogenase [nad(p)+] activity
Specific Function:
Oxidizes medium and long chain saturated and unsaturated aldehydes. Metabolizes also benzaldehyde. Low activity towards acetaldehyde and 3,4-dihydroxyphenylacetaldehyde. May not metabolize short chain aldehydes. May use both NADP(+) and NAD(+) as cofactors. May have a protective role against the cytotoxicity induced by lipid peroxidation.
Gene Name:
ALDH3B1
Uniprot ID:
P43353
Molecular Weight:
51839.245 Da
References
  1. Bunting KD, Townsend AJ: Dependence of aldehyde dehydrogenase-mediated oxazaphosphorine resistance on soluble thiols: importance of thiol interactions with the secondary metabolite acrolein. Biochem Pharmacol. 1998 Jul 1;56(1):31-9. [9698086 ]
General Function:
Aldehyde dehydrogenase [nad(p)+] activity
Specific Function:
Not Available
Gene Name:
ALDH3B2
Uniprot ID:
P48448
Molecular Weight:
42634.6 Da
References
  1. Bunting KD, Townsend AJ: Dependence of aldehyde dehydrogenase-mediated oxazaphosphorine resistance on soluble thiols: importance of thiol interactions with the secondary metabolite acrolein. Biochem Pharmacol. 1998 Jul 1;56(1):31-9. [9698086 ]
General Function:
Benzaldehyde dehydrogenase (nad+) activity
Specific Function:
ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde. They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation. This protein preferentially oxidizes aromatic aldehyde substrates. It may play a role in the oxidation of toxic aldehydes.
Gene Name:
ALDH3A1
Uniprot ID:
P30838
Molecular Weight:
50394.57 Da
References
  1. Bunting KD, Townsend AJ: Dependence of aldehyde dehydrogenase-mediated oxazaphosphorine resistance on soluble thiols: importance of thiol interactions with the secondary metabolite acrolein. Biochem Pharmacol. 1998 Jul 1;56(1):31-9. [9698086 ]
General Function:
Electron carrier activity
Specific Function:
Not Available
Gene Name:
ALDH2
Uniprot ID:
P05091
Molecular Weight:
56380.93 Da
References
  1. Yoval-Sanchez B, Rodriguez-Zavala JS: Differences in susceptibility to inactivation of human aldehyde dehydrogenases by lipid peroxidation byproducts. Chem Res Toxicol. 2012 Mar 19;25(3):722-9. doi: 10.1021/tx2005184. Epub 2012 Feb 29. [22339434 ]
General Function:
Not Available
Specific Function:
Not Available
Gene Name:
SNCA
Uniprot ID:
P37840
Molecular Weight:
14460.155 Da
References
  1. Shamoto-Nagai M, Maruyama W, Hashizume Y, Yoshida M, Osawa T, Riederer P, Naoi M: In parkinsonian substantia nigra, alpha-synuclein is modified by acrolein, a lipid-peroxidation product, and accumulates in the dopamine neurons with inhibition of proteasome activity. J Neural Transm. 2007;114(12):1559-67. Epub 2007 Aug 10. [17690948 ]
General Function:
Transition metal ion binding
Specific Function:
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).
Gene Name:
APP
Uniprot ID:
P05067
Molecular Weight:
86942.715 Da
References
  1. Seidler NW, Squire TJ: Abeta-polyacrolein aggregates: novel mechanism of plastic formation in senile plaques. Biochem Biophys Res Commun. 2005 Sep 23;335(2):501-4. [16081039 ]
General Function:
Phospholipid transporter activity
Specific Function:
Participates in the reverse transport of cholesterol from tissues to the liver for excretion by promoting cholesterol efflux from tissues and by acting as a cofactor for the lecithin cholesterol acyltransferase (LCAT). As part of the SPAP complex, activates spermatozoa motility.
Gene Name:
APOA1
Uniprot ID:
P02647
Molecular Weight:
30777.58 Da
References
  1. Shao B, Fu X, McDonald TO, Green PS, Uchida K, O'Brien KD, Oram JF, Heinecke JW: Acrolein impairs ATP binding cassette transporter A1-dependent cholesterol export from cells through site-specific modification of apolipoprotein A-I. J Biol Chem. 2005 Oct 28;280(43):36386-96. Epub 2005 Aug 25. [16126721 ]
General Function:
Methyltransferase activity
Specific Function:
Not Available
Gene Name:
ALDH1L1
Uniprot ID:
O75891
Molecular Weight:
98828.505 Da
References
  1. Bunting KD, Townsend AJ: Dependence of aldehyde dehydrogenase-mediated oxazaphosphorine resistance on soluble thiols: importance of thiol interactions with the secondary metabolite acrolein. Biochem Pharmacol. 1998 Jul 1;56(1):31-9. [9698086 ]
General Function:
Medium-chain-aldehyde dehydrogenase activity
Specific Function:
Catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acids. Active on a variety of saturated and unsaturated aliphatic aldehydes between 6 and 24 carbons in length. Responsible for conversion of the sphingosine 1-phosphate (S1P) degradation product hexadecenal to hexadecenoic acid.
Gene Name:
ALDH3A2
Uniprot ID:
P51648
Molecular Weight:
54847.36 Da
References
  1. Bunting KD, Townsend AJ: Dependence of aldehyde dehydrogenase-mediated oxazaphosphorine resistance on soluble thiols: importance of thiol interactions with the secondary metabolite acrolein. Biochem Pharmacol. 1998 Jul 1;56(1):31-9. [9698086 ]
General Function:
S-nitrosoglutathione binding
Specific Function:
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.
Gene Name:
GSTP1
Uniprot ID:
P09211
Molecular Weight:
23355.625 Da
References
  1. van Iersel ML, Ploemen JP, Lo Bello M, Federici G, van Bladeren PJ: Interactions of alpha, beta-unsaturated aldehydes and ketones with human glutathione S-transferase P1-1. Chem Biol Interact. 1997 Dec 12;108(1-2):67-78. [9463521 ]
General Function:
Peptidyl-cysteine s-nitrosylase activity
Specific Function:
Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.
Gene Name:
GAPDH
Uniprot ID:
P04406
Molecular Weight:
36053.0 Da
References
  1. Martyniuk CJ, Fang B, Koomen JM, Gavin T, Zhang L, Barber DS, Lopachin RM: Molecular mechanism of glyceraldehyde-3-phosphate dehydrogenase inactivation by alpha,beta-unsaturated carbonyl derivatives. Chem Res Toxicol. 2011 Dec 19;24(12):2302-11. doi: 10.1021/tx200437y. Epub 2011 Nov 29. [22084934 ]
General Function:
Scaffold protein binding
Specific Function:
Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Participates also in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities. Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP. Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor (PubMed:15084260).
Gene Name:
CHUK
Uniprot ID:
O15111
Molecular Weight:
84638.88 Da
References
  1. Kaphalia BS, Ansari GA: Covalent binding of ethylene dibromide and its metabolites to albumin. Toxicol Lett. 1992 Sep;62(2-3):221-30. [1412507 ]
General Function:
Scaffold protein binding
Specific Function:
Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation.
Gene Name:
IKBKB
Uniprot ID:
O14920
Molecular Weight:
86563.245 Da
References
  1. Kaphalia BS, Ansari GA: Covalent binding of ethylene dibromide and its metabolites to albumin. Toxicol Lett. 1992 Sep;62(2-3):221-30. [1412507 ]
General Function:
Ubiquitin protein ligase binding
Specific Function:
Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at 'Ser-708'. Phosphorylation of STAT1 at 'Ser-708' seems also to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Phosphorylates AKT1.
Gene Name:
IKBKE
Uniprot ID:
Q14164
Molecular Weight:
80461.665 Da
References
  1. Kaphalia BS, Ansari GA: Covalent binding of ethylene dibromide and its metabolites to albumin. Toxicol Lett. 1992 Sep;62(2-3):221-30. [1412507 ]
General Function:
Zinc ion binding
Specific Function:
Seems to specifically activate progelatinase A. May thus trigger invasion by tumor cells by activating progelatinase A on the tumor cell surface. May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a positive regulator of cell growth and migration via activation of MMP15. Involved in the formation of the fibrovascular tissues in association with pro-MMP2.
Gene Name:
MMP14
Uniprot ID:
P50281
Molecular Weight:
65893.445 Da
References
  1. Deshmukh HS, McLachlan A, Atkinson JJ, Hardie WD, Korfhagen TR, Dietsch M, Liu Y, Di PY, Wesselkamper SC, Borchers MT, Leikauf GD: Matrix metalloproteinase-14 mediates a phenotypic shift in the airways to increase mucin production. Am J Respir Crit Care Med. 2009 Nov 1;180(9):834-45. doi: 10.1164/rccm.200903-0328OC. Epub 2009 Aug 6. [19661247 ]
General Function:
Methyltransferase activity
Specific Function:
Not Available
Gene Name:
ALDH1L2
Uniprot ID:
Q3SY69
Molecular Weight:
101744.98 Da
References
  1. Bunting KD, Townsend AJ: Dependence of aldehyde dehydrogenase-mediated oxazaphosphorine resistance on soluble thiols: importance of thiol interactions with the secondary metabolite acrolein. Biochem Pharmacol. 1998 Jul 1;56(1):31-9. [9698086 ]
General Function:
Ubiquitin protein ligase binding
Specific Function:
Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. However, the specific type of polyubiquitin recognized upon cell stimulation (either 'Lys-63'-linked or linear polyubiquitin) and its functional importance is reported conflictingly. Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Essential for viral activation of IRF3. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination.
Gene Name:
IKBKG
Uniprot ID:
Q9Y6K9
Molecular Weight:
48197.35 Da
References
  1. Kaphalia BS, Ansari GA: Covalent binding of ethylene dibromide and its metabolites to albumin. Toxicol Lett. 1992 Sep;62(2-3):221-30. [1412507 ]
General Function:
Retinal dehydrogenase activity
Specific Function:
Recognizes as substrates free retinal and cellular retinol-binding protein-bound retinal. Does metabolize octanal and decanal but does not metabolize citral, benzaldehyde, acetaldehyde and propanal efficiently (By similarity).
Gene Name:
ALDH1A2
Uniprot ID:
O94788
Molecular Weight:
56723.495 Da
References
  1. Bunting KD, Townsend AJ: Dependence of aldehyde dehydrogenase-mediated oxazaphosphorine resistance on soluble thiols: importance of thiol interactions with the secondary metabolite acrolein. Biochem Pharmacol. 1998 Jul 1;56(1):31-9. [9698086 ]
General Function:
Succinate-semialdehyde dehydrogenase [nad(p)+] activity
Specific Function:
Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
Gene Name:
ALDH5A1
Uniprot ID:
P51649
Molecular Weight:
57214.23 Da
References
  1. Bunting KD, Townsend AJ: Dependence of aldehyde dehydrogenase-mediated oxazaphosphorine resistance on soluble thiols: importance of thiol interactions with the secondary metabolite acrolein. Biochem Pharmacol. 1998 Jul 1;56(1):31-9. [9698086 ]
General Function:
Protein disulfide oxidoreductase activity
Specific Function:
Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. Plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity. Induces the FOS/JUN AP-1 DNA-binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity.ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55).
Gene Name:
TXN
Uniprot ID:
P10599
Molecular Weight:
11737.42 Da
References
  1. Myers CR, Myers JM: The effects of acrolein on peroxiredoxins, thioredoxins, and thioredoxin reductase in human bronchial epithelial cells. Toxicology. 2009 Mar 4;257(1-2):95-104. doi: 10.1016/j.tox.2008.12.013. Epub 2008 Dec 24. [19135121 ]
General Function:
Thioredoxin-disulfide reductase activity
Specific Function:
Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid.
Gene Name:
TXNRD1
Uniprot ID:
Q16881
Molecular Weight:
70905.58 Da
References
  1. Myers CR, Myers JM: The effects of acrolein on peroxiredoxins, thioredoxins, and thioredoxin reductase in human bronchial epithelial cells. Toxicology. 2009 Mar 4;257(1-2):95-104. doi: 10.1016/j.tox.2008.12.013. Epub 2008 Dec 24. [19135121 ]
General Function:
Thioredoxin-disulfide reductase activity
Specific Function:
Maintains thioredoxin in a reduced state. Implicated in the defenses against oxidative stress. May play a role in redox-regulated cell signaling.
Gene Name:
TXNRD2
Uniprot ID:
Q9NNW7
Molecular Weight:
56506.275 Da
References
  1. Myers CR, Myers JM: The effects of acrolein on peroxiredoxins, thioredoxins, and thioredoxin reductase in human bronchial epithelial cells. Toxicology. 2009 Mar 4;257(1-2):95-104. doi: 10.1016/j.tox.2008.12.013. Epub 2008 Dec 24. [19135121 ]
General Function:
Thioredoxin-disulfide reductase activity
Specific Function:
Displays thioredoxin reductase, glutaredoxin and glutathione reductase activities. Catalyzes disulfide bond isomerization. Promotes disulfide bond formation between GPX4 and various sperm proteins and may play a role in sperm maturation by promoting formation of sperm structural components (By similarity).
Gene Name:
TXNRD3
Uniprot ID:
Q86VQ6
Molecular Weight:
70682.52 Da
References
  1. Myers CR, Myers JM: The effects of acrolein on peroxiredoxins, thioredoxins, and thioredoxin reductase in human bronchial epithelial cells. Toxicology. 2009 Mar 4;257(1-2):95-104. doi: 10.1016/j.tox.2008.12.013. Epub 2008 Dec 24. [19135121 ]
General Function:
Protein disulfide oxidoreductase activity
Specific Function:
Has an anti-apoptotic function and plays an important role in the regulation of mitochondrial membrane potential. Could be involved in the resistance to anti-tumor agents. Possesses a dithiol-reducing activity.
Gene Name:
TXN2
Uniprot ID:
Q99757
Molecular Weight:
18383.165 Da
References
  1. Myers CR, Myers JM: The effects of acrolein on peroxiredoxins, thioredoxins, and thioredoxin reductase in human bronchial epithelial cells. Toxicology. 2009 Mar 4;257(1-2):95-104. doi: 10.1016/j.tox.2008.12.013. Epub 2008 Dec 24. [19135121 ]
General Function:
Transcriptional activator activity, rna polymerase ii transcription factor binding
Specific Function:
Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'. Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation.
Gene Name:
JUN
Uniprot ID:
P05412
Molecular Weight:
35675.32 Da
References
  1. Biswal S, Acquaah-Mensah G, Datta K, Wu X, Kehrer JP: Inhibition of cell proliferation and AP-1 activity by acrolein in human A549 lung adenocarcinoma cells due to thiol imbalance and covalent modifications. Chem Res Toxicol. 2002 Feb;15(2):180-6. [11849044 ]