Arsenic
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Basic Info
| Common Name | Arsenic(F03267) |
| 2D Structure | |
| Description | Arsenic(As) is a ubiquitous metalloid found in several forms in food and the environment, such as the soil, air and water. Physiologically, it exists as an ion in the body. The predominant form is inorganic arsenic in drinking water, which is both highly toxic and carcinogenic and rapidly bioavailable. Arsenic is currently one of the most important environmental global contaminants and toxicants, particularly in the developing countries. For decades, very large populations have been and are currently still exposed to inorganic Arsenic through geogenically contaminated drinking water. An increased incidence of disease mediated by this toxicant is the consequence of long-term exposure. In human's chronic ingestion of inorganic arsenic (> 500 mg/L As) has been associated with cardiovascular, nervous, hepatic and renal diseases and diabetes mellitus as well as cancer of the skin, bladder, lung, liver and prostate. Contrary to the earlier view that methylated compounds are innocuous, the methylated metabolites are now recognized to be both toxic and carcinogenic, possibly due to genotoxicity, inhibition of antioxidative enzyme functions, or other mechanisms. Arsenic inhibits indirectly sulfhydryl containing enzymes and interferes with cellular metabolism. Effects involve such phenomena as cytotoxicity, genotoxicity and inhibition of enzymes with antioxidant function. These are all related to nutritional factors directly or indirectly. Nutritional studies both in experimental and epidemiological studies provide convincing evidence that nutritional intervention, including chemoprevention, offers a pragmatic approach to mitigate the health effects of arsenic exposure, particularly cancer, in the relatively resource-poor developing countries. Nutritional intervention, especially with micronutrients, many of which are antioxidants and share the same pathway with Arsenic , appears a host defence against the health effects of arsenic contamination in developing countries and should be embraced as it is pragmatic and inexpensive. (A7664, A7665). |
| FRCD ID | F03267 |
| CAS Number | 7440-38-2 |
| PubChem CID | 104734 |
| Formula | As+3 |
| IUPAC Name | arsenic(3+) |
| InChI Key | LULLIKNODDLMDQ-UHFFFAOYSA-N |
| InChI | InChI=1S/As/q+3 |
| Canonical SMILES | [As+3] |
| Isomeric SMILES | [As+3] |
| Wikipedia | Arsenic |
| Synonyms |
Arsenic(3+) ion
Arsenic (III)
arsenic(3+)
UNII-C96613F5AV
C96613F5AV
22541-54-4
Arsenic III
Arsenic(3+)ions
Arsenic(+3)
Arsenic ion (3+)
|
| Classifies |
Pollutant
Pesticide
Metal
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Inorganic compounds |
| Superclass | Homogeneous metal compounds |
| Class | Homogeneous metalloid compounds |
| Subclass | Not available |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Homogeneous metalloid compounds |
| Alternative Parents | |
| Molecular Framework | Not available |
| Substituents | Homogeneous metalloid |
| Description | This compound belongs to the class of inorganic compounds known as homogeneous metalloid compounds. These are inorganic compounds containing only metal atoms,with the largest atom being a metalloid atom. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 74.922 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 0 |
| Rotatable Bond Count | 0 |
| Complexity | 0 |
| Monoisotopic Mass | 74.922 |
| Exact Mass | 74.922 |
| Formal Charge | 3 |
| Heavy Atom Count | 1 |
| 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 |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Probabilistic Integrated Human Mixture Risk Assessment of Multiple Metals Through Seafood Consumption. | Risk Anal | 2018 Sep 3 | 30176170 |
| Selenium amelioration of arsenic toxicity in rice shows genotypic variation: A transcriptomic and biochemical analysis. | J Plant Physiol | 2018 Sep 27 | 30278313 |
| An IncX1 plasmid isolated from Salmonella enterica subsp. enterica serovar Pullorum carrying bla<sub>TEM-1B</sub>, sul2, arsenic resistant operons. | Plasmid | 2018 Sep 21 | 30248363 |
| Contaminants in Grain-A Major Risk for Whole Grain Safety? | Nutrients | 2018 Sep 2 | 30200531 |
| Long term insight into biodiversity of a smelter wasteland reclaimed with biosolids and by-product lime. | Sci Total Environ | 2018 Sep 15 | 29913567 |
| WITHDRAWN: Toxic effects of gestational arsenic trioxide on the neuroendocrine axis of developing rats. | Food Chem Toxicol | 2018 Sep 12 | 30218683 |
| Heavy metal and microbial safety assessment of raw and cooked pumpkin and <i>Amaranthus viridis</i> leaves grown in Abakaliki, Nigeria. | Food Sci Nutr | 2018 Sep | 30258596 |
| Expression of rice MATE family transporter OsMATE2 modulates arsenic accumulation in tobacco and rice. | Plant Mol Biol | 2018 Sep | 30121733 |
| Hepatorenal protective effects of medicinal herbs in An-Gong-Niu-Huang Wan (AGNH) against cinnabar- and realgar-induced oxidative stress and inflammatory damage in mice. | Food Chem Toxicol | 2018 Sep | 29203196 |
| Phytotoxicity of polymetallic mine wastes from southern Tuscany and Saxony. | Ecotoxicol Environ Saf | 2018 Oct 30 | 30015197 |
| Impurity profiling of the most frequently encountered falsified polypeptide drugs on the Belgian market. | Talanta | 2018 Oct 1 | 30029448 |
| High-density element concentrations in fish from subtidal to hadal zones of the Pacific Ocean. | Heliyon | 2018 Oct | 30320235 |
| Health Risk Assessment of Exposure to Heavy Metals and Aflatoxins via Dietary Intake of Dried Red Pepper from Marketplaces in Antalya, Southern Turkey. | J Food Sci | 2018 Oct | 30178501 |
| Risk assessment for potentially toxic metal(loid)s in potatoes in the indigenous zinc smelting area of northwestern Guizhou Province, China. | Food Chem Toxicol | 2018 Oct | 30016697 |
| High risk for neural tube defects; the role of arsenic in drinking water and rice in Asia. | Med Hypotheses | 2018 Oct | 30122498 |
| Oral bioaccessibility of toxic and essential elements in raw and cooked commercial seafood species available in European markets. | Food Chem | 2018 Nov 30 | 29934150 |
| Use of hydrolytic enzymes as green and effective extraction agents for ultrasound assisted-enzyme based hydrolytic water phase microextraction of arsenic in food samples. | Talanta | 2018 Nov 1 | 30086922 |
| The bivalve Ruditapes decussatus: A biomonitor of trace elements pollution in Sardinian coastal lagoons (Italy). | Environ Pollut | 2018 Nov | 30064872 |
| C. elegans Development and Activity Test detects mammalian developmental neurotoxins. | Food Chem Toxicol | 2018 Nov | 30266317 |
| 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 |
Targets
- 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:
- 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:
- 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:
- 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.
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:
- 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 ]
- 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:
- Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.
- Gene Name:
- MT1A
- Uniprot ID:
- P04731
- Molecular Weight:
- 6120.19 Da
References
- Ngu TT, Stillman MJ: Arsenic binding to human metallothionein. J Am Chem Soc. 2006 Sep 27;128(38):12473-83. [16984198 ]
- 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 ]
- 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:
- 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:
- 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:
- Pyruvate kinase activity
- Specific Function:
- Glycolytic enzyme that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP. Stimulates POU5F1-mediated transcriptional activation. Plays a general role in caspase independent cell death of tumor cells. The ratio betwween the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production. The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival.
- Gene Name:
- PKM
- Uniprot ID:
- P14618
- Molecular Weight:
- 57936.38 Da
References
- Zhang X, Yang F, Shim JY, Kirk KL, Anderson DE, Chen X: Identification of arsenic-binding proteins in human breast cancer cells. Cancer Lett. 2007 Sep 18;255(1):95-106. Epub 2007 May 17. [17499915 ]
- 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:
- 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:
- 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:
- 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:
- 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:
- 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. 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:
- 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:
- 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:
- 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:
- 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:
- 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:
- 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:
- 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:
- 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:
- 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 ]