Dimethylarsinate
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Basic Info
| Common Name | Dimethylarsinate(F03328) |
| 2D Structure | |
| Description | Cacodylic acid is the chemical compound with the formula (CH3)2AsO2H. Derivatives of cacodylic acid, cacodylates, were frequently used as herbicides. For example, Agent Blue, one of the chemicals used during the Vietnam War, is a mixture of cacodylic acid and sodium cacodylate. Sodium cacodylate is frequently used as a buffering agent in the preparation and fixation of biological samples for transmission electron microscopy. Cacodylic acid is highly toxic by ingestion, inhalation, or skin contact. Once thought to be a byproduct of inorganic arsenic detoxification, it is now believed to have serious health consequences of its own. It has been shown to be teratogenic in rodents, most often causing cleft palate but also fetal fatality at high doses. It has been shown to be genotoxic in human cells, causing apoptosis and also decreased DNA production and shorter DNA strands. While not itself a strong carcinogen, cacodylic acid does promote tumors in the presence of carcinogens in organs such as the kidneys and liver. (Wikipedia). |
| FRCD ID | F03328 |
| CAS Number | 15132-04-4 |
| PubChem CID | 167250 |
| Formula | C2H6AsO2- |
| IUPAC Name | dimethylarsinate |
| InChI Key | OGGXGZAMXPVRFZ-UHFFFAOYSA-M |
| InChI | InChI=1S/C2H7AsO2/c1-3(2,4)5/h1-2H3,(H,4,5)/p-1 |
| Canonical SMILES | C[As](=O)(C)[O-] |
| Isomeric SMILES | C[As](=O)(C)[O-] |
| Wikipedia | Dimethylarsinate |
| Synonyms |
Cacodylate Ion
Cacodylate ions
Dimethylarsinate
Cacodylate
Arsinic acid, dimethyl-, ion(1-)
Bolate
Bolls
15132-04-4
Dimethylarsonic Acid
rad-e-cat 25
|
| Classifies |
Pesticide
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organometallic compounds |
| Class | Organometalloid compounds |
| Subclass | Organoarsenic compounds |
| Intermediate Tree Nodes | Pentavalent organic arsenic compounds |
| Direct Parent | Pentaorganoarsanes |
| Alternative Parents | |
| Molecular Framework | Aliphatic acyclic compounds |
| Substituents | Pentaorganoarsane - Alkylarsine oxide - Oxygen-containing organoarsenic compound - Organic metalloid salt - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organic salt - Organic anion - Aliphatic acyclic compound |
| Description | This compound belongs to the class of organic compounds known as pentaorganoarsanes. These are organoarsenic compounds containing an arsenic compound that is pentasubstituted by only organic groups. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 136.99 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 0 |
| Complexity | 53.8 |
| Monoisotopic Mass | 136.958 |
| Exact Mass | 136.958 |
| Formal Charge | -1 |
| Heavy Atom Count | 5 |
| 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+ | 0.9719 |
| Human Intestinal Absorption | HIA+ | 0.8303 |
| Caco-2 Permeability | Caco2+ | 0.5475 |
| P-glycoprotein Substrate | Non-substrate | 0.7957 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9747 |
| Non-inhibitor | 0.9937 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9354 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.5948 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8150 |
| CYP450 2D6 Substrate | Non-substrate | 0.8668 |
| CYP450 3A4 Substrate | Non-substrate | 0.6150 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.8630 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.8946 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9429 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.8964 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.9835 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9726 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9368 |
| Non-inhibitor | 0.9478 | |
| AMES Toxicity | Non AMES toxic | 0.9087 |
| Carcinogens | Carcinogens | 0.7064 |
| Fish Toxicity | Low FHMT | 0.9248 |
| Tetrahymena Pyriformis Toxicity | Low TPT | 0.9560 |
| Honey Bee Toxicity | High HBT | 0.6683 |
| Biodegradation | Not ready biodegradable | 0.5054 |
| Acute Oral Toxicity | III | 0.5120 |
| Carcinogenicity (Three-class) | Non-required | 0.6283 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -0.6899 | LogS |
| Caco-2 Permeability | 1.1628 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 1.8518 | LD50, mol/kg |
| Fish Toxicity | 3.0774 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | -1.8967 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Metabolism and disposition of arsenic species from controlled dosing with sodium arsenite in adult female CD-1 mice. III. Toxicokinetic studies following oral and intravenous administration. | Food Chem Toxicol | 2018 Nov | 30278242 |
| Impact of prenatal arsenic exposure on chronic adult diseases. | Syst Biol Reprod Med | 2018 Jun 6 | 29873257 |
| Accumulation, translocation and conversion of six arsenic species in rice plants grown near a mine impacted city. | Chemosphere | 2017 Sep | 28531558 |
| Nitarsone, Inorganic Arsenic, and Other Arsenic Species in Turkey Meat: Exposure and Risk Assessment Based on a 2014 U.S. Market Basket Sample. | Environ Health Perspect | 2017 Mar | 27735789 |
| Sample preparation for arsenic speciation analysis in baby food by generation of substituted arsines with atomic absorption spectrometry detection. | Talanta | 2017 Dec 1 | 28842009 |
| Trace elements and arsenic speciation in tissues of tube dwelling polychaetesfrom hydrothermal vent ecosystems (East Pacific Rise): An ecological role asantipredatory strategy? | Mar Environ Res | 2017 Dec | 29037570 |
| A study on toxic and essential elements in rice from the Republic of Kazakhstan: comparing the level of contamination in rice from the European Community. | Environ Geochem Health | 2016 Feb | 25750053 |
| Simultaneous determination of arsenic and mercury species in rice by ion-pairing reversed phase chromatography with inductively coupled plasma mass spectrometry. | Food Chem | 2016 Dec 15 | 27451225 |
| Metabolism and toxicity of arsenicals in mammals. | Environ Toxicol Pharmacol | 2016 Dec | 27829199 |
| Arsenic in the human food chain, biotransformation and toxicology--Review focusing on seafood arsenic. | J Trace Elem Med Biol | 2015 | 25666158 |
| Graphene oxide amplifies the phytotoxicity of arsenic in wheat. | Sci Rep | 2014 Aug 19 | 25134726 |
| Toxicological properties of the thiolated inorganic arsenic and arsenosugar metabolite thio-dimethylarsinic acid in human bladder cells. | J Trace Elem Med Biol | 2014 Apr | 23994116 |
| In vitro toxicological characterisation of the S-containing arsenic metabolites thio-dimethylarsinic acid and dimethylarsinic glutathione. | Toxicology | 2013 Mar 8 | 23353027 |
| In vitro toxicological characterization of two arsenosugars and their metabolites. | Mol Nutr Food Res | 2013 Jul | 23564523 |
| Levels and chemical speciation of arsenic in representative biota and sediments of a tropical mangrove wetland, India. | Environ Sci Process Impacts | 2013 Apr | 23400359 |
| Major and minor arsenic compounds accounting for the total urinary excretion of arsenic following intake of blue mussels (Mytilus edulis): a controlled human study. | Food Chem Toxicol | 2012 Jul | 22546366 |
| Arsenic-containing lipids are natural constituents of sashimi tuna. | Environ Sci Technol | 2010 Feb 15 | 20099809 |
| Sample preparation strategies for one- and two-dimensional gel electrophoreticseparation of plant proteins and the influence on arsenic and zinc bindings. | J Chromatogr B Analyt Technol Biomed Life Sci | 2009 Oct 1 | 19733519 |
| Determination of arsenic and mercury in sunflower oil by electrothermal atomicabsorption. | Food Addit Contam | 2002 Oct | 12443556 |
Targets
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
- Gene Name:
- ACTA1
- Uniprot ID:
- P68133
- Molecular Weight:
- 42050.67 Da
- Mechanism of Action:
- Arsenic binds to actin.
References
- Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
- General Function:
- Protein kinase binding
- Specific Function:
- Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
- Gene Name:
- ACTA2
- Uniprot ID:
- P62736
- Molecular Weight:
- 42008.57 Da
- Mechanism of Action:
- Arsenic binds to actin.
References
- Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
- General Function:
- Tat protein binding
- Specific Function:
- Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
- Gene Name:
- ACTB
- Uniprot ID:
- P60709
- Molecular Weight:
- 41736.37 Da
- Mechanism of Action:
- Arsenic binds to actin.
References
- Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
- General Function:
- Ubiquitin protein ligase binding
- Specific Function:
- Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
- Gene Name:
- ACTG1
- Uniprot ID:
- P63261
- Molecular Weight:
- 41792.48 Da
- Mechanism of Action:
- Arsenic binds to actin.
References
- Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
- General Function:
- Atp binding
- Specific Function:
- Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
- Gene Name:
- ACTG2
- Uniprot ID:
- P63267
- Molecular Weight:
- 41876.495 Da
- Mechanism of Action:
- Arsenic binds to actin.
References
- Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
- General Function:
- Ubiquitin protein ligase binding
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Gene Name:
- TUBB
- Uniprot ID:
- P07437
- Molecular Weight:
- 49670.515 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Signal transducer activity
- Specific Function:
- Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Transducin is an amplifier and one of the transducers of a visual impulse that performs the coupling between rhodopsin and cGMP-phosphodiesterase.
- Gene Name:
- GNAT1
- Uniprot ID:
- P11488
- Molecular Weight:
- 40040.415 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Tetrahydrobiopterin binding
- Specific Function:
- Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.
- Gene Name:
- NOS3
- Uniprot ID:
- P29474
- Molecular Weight:
- 133287.62 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Glyceraldehyde oxidoreductase activity
- Specific Function:
- Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
- Gene Name:
- AKR1B1
- Uniprot ID:
- P15121
- Molecular Weight:
- 35853.125 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- General Function:
- Myosin binding
- Specific Function:
- Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
- Gene Name:
- ACTC1
- Uniprot ID:
- P68032
- Molecular Weight:
- 42018.6 Da
- Mechanism of Action:
- Arsenic binds to actin.
References
- Menzel DB, Hamadeh HK, Lee E, Meacher DM, Said V, Rasmussen RE, Greene H, Roth RN: Arsenic binding proteins from human lymphoblastoid cells. Toxicol Lett. 1999 Mar 29;105(2):89-101. [10221271 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
- Gene Name:
- ESR1
- Uniprot ID:
- P03372
- Molecular Weight:
- 66215.45 Da
- Mechanism of Action:
- Arsenic binds to the estrogen receptor.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- 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:
- Arsenic binds thioredoxin reductase, which results in the inhibition of essential biochemical reactions, alteration of cellular redox status, and eventual cytotoxicity.
References
- ATSDR - Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for arsenic. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). : http://www.atsdr.cdc.gov/toxprofiles/tp2.html
- General Function:
- Zinc ion binding
- Specific Function:
- Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic genes expression.
- Gene Name:
- NR3C1
- Uniprot ID:
- P04150
- Molecular Weight:
- 85658.57 Da
- Mechanism of Action:
- Arsenic binds to the glucocorticoid receptor. (A17
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Nadp binding
- Specific Function:
- Maintains high levels of reduced glutathione in the cytosol.
- Gene Name:
- GSR
- Uniprot ID:
- P00390
- Molecular Weight:
- 56256.565 Da
- Mechanism of Action:
- Arsenic binds glutathione reductase, which results in the inhibition of essential biochemical reactions, alteration of cellular redox status, and eventual cytotoxicity.
References
- ATSDR - Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for arsenic. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). : http://www.atsdr.cdc.gov/toxprofiles/tp2.html
- General Function:
- Oxygen transporter activity
- Specific Function:
- Involved in oxygen transport from the lung to the various peripheral tissues.
- Gene Name:
- HBA1
- Uniprot ID:
- P69905
- Molecular Weight:
- 15257.405 Da
- Mechanism of Action:
- Arsenic binds to hemoglobin.
References
- Naranmandura H, Suzuki KT: Identification of the major arsenic-binding protein in rat plasma as the ternary dimethylarsinous-hemoglobin-haptoglobin complex. Chem Res Toxicol. 2008 Mar;21(3):678-85. doi: 10.1021/tx700383g. Epub 2008 Feb 2. [18247522 ]
- General Function:
- Oxygen transporter activity
- Specific Function:
- Involved in oxygen transport from the lung to the various peripheral tissues.LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure.Spinorphin: functions as an endogenous inhibitor of enkephalin-degrading enzymes such as DPP3, and as a selective antagonist of the P2RX3 receptor which is involved in pain signaling, these properties implicate it as a regulator of pain and inflammation.
- Gene Name:
- HBB
- Uniprot ID:
- P68871
- Molecular Weight:
- 15998.34 Da
- Mechanism of Action:
- Arsenic binds to hemoglobin.
References
- Naranmandura H, Suzuki KT: Identification of the major arsenic-binding protein in rat plasma as the ternary dimethylarsinous-hemoglobin-haptoglobin complex. Chem Res Toxicol. 2008 Mar;21(3):678-85. doi: 10.1021/tx700383g. Epub 2008 Feb 2. [18247522 ]
- Uniprot ID:
- A6NKZ8
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- Uniprot ID:
- Q99867
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Gene Name:
- TUBA4B
- Uniprot ID:
- Q9H853
- Molecular Weight:
- 27551.01 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Pyruvate dehydrogenase (acetyl-transferring) activity
- Specific Function:
- The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
- Gene Name:
- PDHA2
- Uniprot ID:
- P29803
- Molecular Weight:
- 42932.855 Da
- Mechanism of Action:
- Arsenic disrupts ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress.
References
- Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.
- General Function:
- Pyruvate dehydrogenase activity
- Specific Function:
- The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
- Gene Name:
- PDHB
- Uniprot ID:
- P11177
- Molecular Weight:
- 39233.1 Da
- Mechanism of Action:
- Arsenic disrupts ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress.
References
- Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.
- General Function:
- Transferase activity, transferring acyl groups
- Specific Function:
- Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is essential for a functional PDH complex.
- Gene Name:
- PDHX
- Uniprot ID:
- O00330
- Molecular Weight:
- 54121.76 Da
- Mechanism of Action:
- Arsenic disrupts ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress.
References
- Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.
- 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:
- Arsenic binds thioredoxin reductase, which results in the inhibition of essential biochemical reactions, alteration of cellular redox status, and eventual cytotoxicity.
References
- ATSDR - Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for arsenic. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). : http://www.atsdr.cdc.gov/toxprofiles/tp2.html
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
- Gene Name:
- TUBAL3
- Uniprot ID:
- A6NHL2
- Molecular Weight:
- 49908.305 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Specific Function:
- Gtp binding
- Gene Name:
- TUBA1A
- Uniprot ID:
- Q71U36
- Molecular Weight:
- 50135.25 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Ubiquitin protein ligase binding
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Gene Name:
- TUBA1B
- Uniprot ID:
- P68363
- Molecular Weight:
- 50151.24 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural molecule activity
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Gene Name:
- TUBA1C
- Uniprot ID:
- Q9BQE3
- Molecular Weight:
- 49894.93 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Gene Name:
- TUBA3C
- Uniprot ID:
- Q13748
- Molecular Weight:
- 49959.145 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
- Gene Name:
- TUBA3E
- Uniprot ID:
- Q6PEY2
- Molecular Weight:
- 49858.135 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Gene Name:
- TUBA4A
- Uniprot ID:
- P68366
- Molecular Weight:
- 49923.995 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Specific Function:
- Gtp binding
- Gene Name:
- TUBA8
- Uniprot ID:
- Q9NY65
- Molecular Weight:
- 50093.12 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
- Gene Name:
- TUBB2A
- Uniprot ID:
- Q13885
- Molecular Weight:
- 49906.67 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity). TUBB2B is implicated in neuronal migration.
- Gene Name:
- TUBB2B
- Uniprot ID:
- Q9BVA1
- Molecular Weight:
- 49952.76 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. TUBB3 plays a critical role in proper axon guidance and mantainance.
- Gene Name:
- TUBB3
- Uniprot ID:
- Q13509
- Molecular Weight:
- 50432.355 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Gene Name:
- TUBB4A
- Uniprot ID:
- P04350
- Molecular Weight:
- 49585.475 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Unfolded protein binding
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Gene Name:
- TUBB4B
- Uniprot ID:
- P68371
- Molecular Weight:
- 49830.72 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
- Gene Name:
- TUBB6
- Uniprot ID:
- Q9BUF5
- Molecular Weight:
- 49856.785 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
- Gene Name:
- TUBB8
- Uniprot ID:
- Q3ZCM7
- Molecular Weight:
- 49775.655 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
- Uniprot ID:
- A6NNZ2
- Molecular Weight:
- 49572.265 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- In the elongating spermatid it is associated with the manchette, a specialized microtubule system present during reshaping of the sperm head.
- Gene Name:
- TUBD1
- Uniprot ID:
- Q9UJT1
- Molecular Weight:
- 51033.86 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Gene Name:
- TUBE1
- Uniprot ID:
- Q9UJT0
- Molecular Weight:
- 52931.4 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural molecule activity
- Specific Function:
- Tubulin is the major constituent of microtubules. The gamma chain is found at microtubule organizing centers (MTOC) such as the spindle poles or the centrosome. Pericentriolar matrix component that regulates alpha/beta chain minus-end nucleation, centrosome duplication and spindle formation (By similarity).
- Gene Name:
- TUBG2
- Uniprot ID:
- Q9NRH3
- Molecular Weight:
- 51091.32 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Interleukin-8 receptor binding
- Specific Function:
- IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response to an inflammatory stimulus. IL-8(6-77) has a 5-10-fold higher activity on neutrophil activation, IL-8(5-77) has increased activity on neutrophil activation and IL-8(7-77) has a higher affinity to receptors CXCR1 and CXCR2 as compared to IL-8(1-77), respectively.
- Gene Name:
- CXCL8
- Uniprot ID:
- P10145
- Molecular Weight:
- 11097.98 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Steroid hydroxylase activity
- Specific Function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
- Gene Name:
- CYP2B6
- Uniprot ID:
- P20813
- Molecular Weight:
- 56277.81 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- Involved in DNA excision repair. Initiates repair by binding to damaged sites with various affinities, depending on the photoproduct and the transcriptional state of the region. Required for UV-induced CHEK1 phosphorylation and the recruitment of CEP164 to cyclobutane pyrimidine dimmers (CPD), sites of DNA damage after UV irradiation.
- Gene Name:
- XPA
- Uniprot ID:
- P23025
- Molecular Weight:
- 31367.71 Da
- Mechanism of Action:
- Arsenic binding of XPA is believed to induce carcinogenesis by affecting DNA repair.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Dihydrolipoyllysine-residue acetyltransferase activity
- Specific Function:
- The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
- Gene Name:
- DLAT
- Uniprot ID:
- P10515
- Molecular Weight:
- 68996.03 Da
- Mechanism of Action:
- Arsenic disrupts ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress.
References
- Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.
- General Function:
- Serine-type endopeptidase activity
- Specific Function:
- As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an Antimicrobial; Antioxidant, has antibacterial activity and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidely cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway.Uncleaved haptoglogin, also known as zonulin, plays a role in intestinal permeability, allowing intercellular tight junction disassembly, and controlling the equilibrium between tolerance and immunity to non-self antigens.
- Gene Name:
- HP
- Uniprot ID:
- P00738
- Molecular Weight:
- 45205.065 Da
- Mechanism of Action:
- Arsenic binds to haptoglobin.
References
- Naranmandura H, Suzuki KT: Identification of the major arsenic-binding protein in rat plasma as the ternary dimethylarsinous-hemoglobin-haptoglobin complex. Chem Res Toxicol. 2008 Mar;21(3):678-85. doi: 10.1021/tx700383g. Epub 2008 Feb 2. [18247522 ]
- General Function:
- Transcription factor binding
- Specific Function:
- Acts as a substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1 and targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. Retains NFE2L2/NRF2 and may also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome.
- Gene Name:
- KEAP1
- Uniprot ID:
- Q14145
- Molecular Weight:
- 69665.765 Da
- Mechanism of Action:
- Arsenic binds to kelch-like ECH-associated protein 1.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Required for PARP9 and DTX3L recruitment to DNA damage sites. PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites.
- Gene Name:
- PARP1
- Uniprot ID:
- P09874
- Molecular Weight:
- 113082.945 Da
- Mechanism of Action:
- Arsenic binding of PARP-1 is believed to induce carcinogenesis by affecting DNA repair.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Pyruvate dehydrogenase activity
- Specific Function:
- The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
- Gene Name:
- PDHA1
- Uniprot ID:
- P08559
- Molecular Weight:
- 43295.255 Da
- Mechanism of Action:
- Arsenic disrupts ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress.
References
- Klaassen C and Watkins J (2003). Casarett and Doull's Essentials of Toxicology. New York, NY: McGraw-Hill.
- 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:
- Arsenic binds thioredoxin reductase, which results in the inhibition of essential biochemical reactions, alteration of cellular redox status, and eventual cytotoxicity.
References
- ATSDR - Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for arsenic. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). : http://www.atsdr.cdc.gov/toxprofiles/tp2.html
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
- Gene Name:
- TUBB1
- Uniprot ID:
- Q9H4B7
- Molecular Weight:
- 50326.56 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Structural constituent of cytoskeleton
- Specific Function:
- Tubulin is the major constituent of microtubules. The gamma chain is found at microtubule organizing centers (MTOC) such as the spindle poles or the centrosome. Pericentriolar matrix component that regulates alpha/beta chain minus-end nucleation, centrosome duplication and spindle formation.
- Gene Name:
- TUBG1
- Uniprot ID:
- P23258
- Molecular Weight:
- 51169.48 Da
- Mechanism of Action:
- Arsenic's carginogenicity is believed to be caused by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests.
References
- Kitchin KT, Wallace K: The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem. 2008 Mar;102(3):532-9. doi: 10.1016/j.jinorgbio.2007.10.021. Epub 2007 Nov 22. [18164070 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- Cytokine that plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone development. Required for normal male and female fertility. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration. Plays a role in lipoprotein clearance.
- Gene Name:
- CSF1
- Uniprot ID:
- P09603
- Molecular Weight:
- 60178.885 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]