Acrolein
(right click,save link as to download,it is a temp file,please download as soon as possible, you can also use CTRL+S to save the whole html page)
Basic Info
| Common Name | Acrolein(F03296) |
| 2D Structure | |
| Description | Acrolein (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. |
| FRCD ID | F03296 |
| CAS Number | 107-02-8 |
| PubChem CID | 7847 |
| Formula | C3H4O |
| IUPAC Name | prop-2-enal |
| InChI Key | HGINCPLSRVDWNT-UHFFFAOYSA-N |
| InChI | InChI=1S/C3H4O/c1-2-3-4/h2-3H,1H2 |
| Canonical SMILES | C=CC=O |
| Isomeric SMILES | C=CC=O |
| Wikipedia | Acrolein |
| Synonyms |
ACROLEIN
Acrylaldehyde
2-Propenal
Propenal
Acrylic aldehyde
107-02-8
Allyl aldehyde
prop-2-enal
Ethylene aldehyde
Acraldehyde
|
| Classifies |
Pollutant
Pesticide
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organic oxygen compounds |
| Class | Organooxygen compounds |
| Subclass | Carbonyl compounds |
| Intermediate Tree Nodes | Alpha,beta-unsaturated carbonyl compounds - Alpha,beta-unsaturated aldehydes |
| Direct Parent | Enals |
| Alternative Parents | |
| Molecular Framework | Aliphatic acyclic compounds |
| Substituents | Enal - Organic oxide - Hydrocarbon derivative - Short-chain aldehyde - Aldehyde - Aliphatic acyclic compound |
| Description | This compound 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. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 56.064 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 1 |
| Rotatable Bond Count | 1 |
| Complexity | 30.3 |
| Monoisotopic Mass | 56.026 |
| Exact Mass | 56.026 |
| XLogP | 0 |
| Formal Charge | 0 |
| Heavy Atom Count | 4 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9810 |
| Human Intestinal Absorption | HIA+ | 0.9882 |
| Caco-2 Permeability | Caco2+ | 0.8095 |
| P-glycoprotein Substrate | Non-substrate | 0.8478 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9438 |
| Non-inhibitor | 0.9721 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9149 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.3390 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8450 |
| CYP450 2D6 Substrate | Non-substrate | 0.9249 |
| CYP450 3A4 Substrate | Non-substrate | 0.8028 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.8095 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9497 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9709 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9209 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.9668 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.8891 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9446 |
| Non-inhibitor | 0.9851 | |
| AMES Toxicity | AMES toxic | 0.9108 |
| Carcinogens | Carcinogens | 0.6695 |
| Fish Toxicity | High FHMT | 0.8970 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9754 |
| Honey Bee Toxicity | High HBT | 0.8389 |
| Biodegradation | Ready biodegradable | 0.5365 |
| Acute Oral Toxicity | I | 0.5145 |
| Carcinogenicity (Three-class) | Non-required | 0.6616 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | 0.1629 | LogS |
| Caco-2 Permeability | 1.7041 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 3.0620 | LD50, mol/kg |
| Fish Toxicity | -0.7224 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 1.7476 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Adducts formed during protein digestion decreased the toxicity of five carbonyl compounds against Caco-2 cells. | J Hazard Mater | 2018 Sep 24 | 30300775 |
| Acrolein-induced autophagy-dependent apoptosis via activation of the lysosomal-mitochondrial pathway in EAhy926 cells. | Toxicol In Vitro | 2018 Oct | 29902662 |
| Risk management of ochratoxigenic fungi and ochratoxin A in maize grains by bioactive EVOH films containing individual components of some essential oils. | Int J Food Microbiol | 2018 Mar 23 | 29421354 |
| Inhibition of quorum sensing-controlled virulence factors and biofilm formation in Pseudomonas fluorescens by cinnamaldehyde. | Int J Food Microbiol | 2018 Mar 23 | 29421365 |
| Acrolein-induced atherogenesis by stimulation of hepatic flavin containing monooxygenase 3 and a protection from hydroxytyrosol. | J Cell Physiol | 2018 Jan | 29953618 |
| Cow's milk neutralizes the cytotoxicity of acrolein, a putative carcinogen in cigarette smoke. | J Vet Med Sci | 2018 Aug 22 | 29937461 |
| Selected plant essential oils and their main active components, a promising approach to inhibit aflatoxigenic fungi and aflatoxin production in food. | Food Addit Contam Part A Chem Anal Control Expo Risk Assess | 2018 Aug | 29338637 |
| Influence of ripeness and maceration of the grapes on levels of furan and carbonyl compounds in wine - Simultaneous quantitative determination and assessment of the exposure risk to these compounds. | Food Chem | 2017 Sep 1 | 28407955 |
| Electronic Cigarettes: Their Constituents and Potential Links to Asthma. | Curr Allergy Asthma Rep | 2017 Oct 5 | 28983782 |
| Antiaflatoxigenic and Antimicrobial Activities of Schiff Bases of 2-Hydroxy-4-methoxybenzaldehyde, Cinnamaldehyde, and Similar Aldehydes. | J Agric Food Chem | 2017 Oct 11 | 28942637 |
| An Electronic Cigarette Vaping Machine for the Characterization of Aerosol Delivery and Composition. | Nicotine Tob Res | 2017 Oct 1 | 27281605 |
| Comparison and characterization of volatile compounds as markers of oils stability during frying by HS-SPME-GC/MS and Chemometric analysis. | J Chromatogr B Analyt Technol Biomed Life Sci | 2017 Nov 15 | 29128279 |
| Coadministration of isomalto-oligosaccharides augments metabolic health benefits of cinnamaldehyde in high fat diet fed mice. | Biofactors | 2017 Nov | 28799667 |
| Diet-induced obesity alters dural CGRP release and potentiates TRPA1-mediatedtrigeminovascular responses. | Cephalalgia | 2017 May | 27301459 |
| Lipidomic analysis for carbonyl species derived from fish oil using liquid chromatography-tandem mass spectrometry. | Talanta | 2017 Jun 1 | 28391860 |
| Acrolein Can Cause Cardiovascular Disease: A Review. | Cardiovasc Toxicol | 2017 Jul | 28084565 |
| Toxicity of Plant Secondary Metabolites Modulating Detoxification Genes Expression for Natural Red Palm Weevil Pesticide Development. | Molecules | 2017 Jan 20 | 28117698 |
| Studies on the Anti-Oxidative Function of trans-Cinnamaldehyde-Included β-Cyclodextrin Complex. | Molecules | 2017 Dec 19 | 29257084 |
| [Atmospheric Pollutant Emission Characteristics from the Cooking Process ofTraditional Beijing Roast Duck]. | Huan Jing Ke Xue | 2017 Aug 8 | 29964919 |
| Impact of bioactive packaging systems based on EVOH films and essential oils in the control of aflatoxigenic fungi and aflatoxin production in maize. | Int J Food Microbiol | 2017 Aug 2 | 28525761 |
Targets
- General Function:
- Aldehyde dehydrogenase [nad(p)+] activity
- Gene Name:
- ALDH3B2
- Uniprot ID:
- P48448
- Molecular Weight:
- 42634.6 Da
- Mechanism of Action:
- Acrolein inhibits aldehyde dehydrogenases.
References
- 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
- Mechanism of Action:
- Acrolein inhibits aldehyde dehydrogenases.
References
- 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
- Gene Name:
- ALDH2
- Uniprot ID:
- P05091
- Molecular Weight:
- 56380.93 Da
References
- 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 ]
- Gene Name:
- SNCA
- Uniprot ID:
- P37840
- Molecular Weight:
- 14460.155 Da
References
- 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:
- 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
- Mechanism of Action:
- Acrolein interferes with normal reverse cholesterol transport by high density lipoprotein (HDL) by modifying specific sites in apolipoprotein A-I.
References
- 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
- Gene Name:
- ALDH1L1
- Uniprot ID:
- O75891
- Molecular Weight:
- 98828.505 Da
- Mechanism of Action:
- Acrolein inhibits aldehyde dehydrogenases.
References
- 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
- Mechanism of Action:
- Acrolein inhibits aldehyde dehydrogenases.
References
- 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
- 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:
- 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
- Mechanism of Action:
- Acrolein inhibits thioredoxin, which disrupts the cellular thiol redox balance necessary for cell survival.
References
- 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:
- 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
- Mechanism of Action:
- 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.
References
- 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:
- Methyltransferase activity
- Gene Name:
- ALDH1L2
- Uniprot ID:
- Q3SY69
- Molecular Weight:
- 101744.98 Da
- Mechanism of Action:
- Acrolein inhibits aldehyde dehydrogenases.
References
- 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:
- 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
- Mechanism of Action:
- Acrolein inhibits aldehyde dehydrogenases.
References
- 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
- Mechanism of Action:
- Acrolein inhibits aldehyde dehydrogenases.
References
- 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
- Mechanism of Action:
- Acrolein inhibits thioredoxin, which disrupts the cellular thiol redox balance necessary for cell survival.
References
- 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
- Mechanism of Action:
- Acrolein inhibits thioredoxin reductase, which disrupts the cellular thiol redox balance necessary for cell survival.
References
- 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
- Mechanism of Action:
- Acrolein inhibits thioredoxin reductase, which disrupts the cellular thiol redox balance necessary for cell survival.
References
- 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
- Mechanism of Action:
- Acrolein inhibits thioredoxin reductase, which disrupts the cellular thiol redox balance necessary for cell survival.
References
- 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
- 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 ]
- 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
- Mechanism of Action:
- Acrolein inhibits aldehyde dehydrogenases.
References
- 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
- Mechanism of Action:
- Acrolein inhibits aldehyde dehydrogenases.
References
- 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:
- 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
- Mechanism of Action:
- Acrolein inhibits aldehyde dehydrogenases.
References
- 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:
- 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
- Mechanism of Action:
- Acrolein activates the transient receptor potential cation channel, causing acute pain.
References
- 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 ]
- 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
- Mechanism of Action:
- Acrolein inhibits aldehyde dehydrogenases.
References
- 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:
- 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
- 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:
- 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
- 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
- Mechanism of Action:
- 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.
References
- 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
- Mechanism of Action:
- 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.
References
- 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
- 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:
- 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
- Mechanism of Action:
- 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.
References
- Kaphalia BS, Ansari GA: Covalent binding of ethylene dibromide and its metabolites to albumin. Toxicol Lett. 1992 Sep;62(2-3):221-30. [1412507 ]