Please note that T3DB is currently undergoing changes to improve data quality and
website features. You can access the original version of T3DB
here.
T3D0128 - Copper
| Record Information | |
|---|---|
| Version | 1.0 |
| Creation Date | 2009-03-06 18:58:08 UTC |
| Update Date | 2013-04-25 08:32:57 UTC |
| Accession Number | T3D0128 |
| Identification | |
| Common Name | Copper |
| Description | Copper is a chemical element with the symbol Cu and atomic number 29. Copper is an essential element in plants and animals as it is required for the normal functioning of more than 30 enzymes. It occurs naturally throughout the environment in rocks, soil, water, and air. It is used as a thermal conductor, an electrical conductor, a building material, and a constituent of various metal alloys such as brass and bronze. Copper compounds are known in several oxidation states, usually 2+, where they often impart blue or green colors to natural minerals such as turquoise and have been used historically widely as pigments. Copper as both metal and pigmented salt, has a significant presence in decorative art. Copper compounds are also commonly used in agriculture to treat plant diseases like mildew, for water treatment and, as preservatives for wood, leather, and fabrics. (R513, R514) |
| Compound Type |
|
| Chemical Structure |
|
| Synonyms |
|
| Chemical Formula | Cu |
| Average Molecular Weight | 63.546 |
| Monoisotopic Molecular Weight | 62.929601079 |
| Chemical IUPAC Name | copper(2+) |
| CAS Registry Number | 7440-50-8 |
| SMILES | [Cu++] |
| InChI Identifier | InChI=1S/Cu/q+2 |
| InChI Key | InChIKey=JPVYNHNXODAKFH-UHFFFAOYSA-N |
| Chemical Taxonomy | |
| Kingdom | Inorganic Compounds |
| Super Class | Homogeneous Metal Compounds |
| Class | Homogeneous Transition Metal Compounds |
| Sub Class | Not Available |
| Direct Parent | Homogeneous Transition Metal Compounds |
| Alternative Parents | Not Available |
| Molecular Framework | Acyclic Compounds |
| Substituents | Not Available |
| External Descriptors |
|
| External Links | |
| DrugBank ID | Not Available |
| PubChem Compound ID | 23978  |
| KEGG ID | C00070 |
| UniProt ID | Not Available |
| OMIM ID | 121270
147450
215600
309400
602268
603085
603088
603735
603864
607238
610101 |
| ChEBI ID | 30052 |
| BioCyc ID | CUCL2 |
| CTD ID | D003300 |
| Stitch ID | Copper |
| PDB ID | Not Available |
| ACToR ID | 6411 |
| Wikipedia Link | http://en.wikipedia.org/wiki/Copper |
| Physical Properties | |
| Appearance | Reddish metallic solid. |
| Melting Point | 1083 C |
| Solubility | Not Available |
| Predicted LogP | 0.156 |
| Toxicity Profile | |
| Route of Exposure | Oral (R513) ; inhalation (R513) ; dermal (R513) |
| Mechanism of Action | Excess copper is sequestered within hepatocyte lysosomes, where it is complexed with metallothionein. Copper hepatotoxicity is believed to occur when the lysosomes become saturated and copper accumulates in the nucleus, causing nuclear damage. This damage is possibly a result of oxidative damage, including lipid peroxidation. Copper inhibits the sulfhydryl group enzymes such as glucose-6-phosphate 1-dehydrogenase, glutathione reductase, and paraoxonases, which protect the cell from free oxygen radicals. It also influences gene expression and is a co-factor for oxidative enzymes such as cytochrome C oxidase and lysyl oxidase. In addition, the oxidative stress induced by copper is thought to activate acid sphingomyelinase, which lead to the production of ceramide, an apoptotic signal, as well as cause hemolytic anemia. Copper-induced emesis results from stimulation of the vagus nerve. (R513, R523, R525, R526) |
| Metabolism | Copper is mainly absorbed through the gastrointestinal tract, but it can also be inhalated and absorbed dermally. It passes through the basolateral membrane, possibly via regulatory copper transporters, and is transported to the liver and kidney bound to serum albumin. The liver is the critical organ for copper homeostasis. In the liver and other tissues, copper is stored bound to metallothionein, amino acids, and in association with copper-dependent enzymes, then partitioned for excretion through the bile or incorporation into intra- and extracellular proteins. The transport of copper to the peripheral tissues is accomplished through the plasma attached to serum albumin, ceruloplasmin or low-molecular-weight complexes. Copper may induce the production of metallothionein and ceruloplasmin. The membrane-bound copper transporting adenosine triphosphatase (Cu-ATPase) transports copper ions into and out of cells. Physiologically normal levels of copper in the body are held constant by alterations in the rate and amount of copper absorption, compartmental distribution, and excretion. (R513, R520) |
| Toxicity Values | LD50: 3500 ug/kg (Intraperitoneal, Mouse) (R293) |
| Lethal Dose | 10 to 20 grams for an adult human. (R273) |
| Carcinogenicity (IARC Classification) | Not Available |
| Uses/Sources | Copper is used as a thermal conductor, an electrical conductor, a building material, and a constituent of various metal alloys such as brass and bronze. Copper compounds have been widely used historically as pigments in decorative art. Copper compounds are also commonly used in agriculture to treat plant diseases like mildew, for water treatment, and as preservatives for wood, leather, and fabrics. (R513, R514) |
| Minimum Risk Level | Acute Oral: 0.01 mg/kg/day (R260) Intermediate Oral: 0.01 mg/kg/day (R260) |
| Health Effects | People must absorb small amounts of copper every day because copper is essential for good health, however, high levels of copper can be harmful. Very-high doses of copper can damage liver and kidneys, and can even cause death. Copper may induce allergic responses in sensitive individuals. (R514, R520) |
| Symptoms | Breathing high levels of copper can cause irritation of the nose and throat. Ingesting high levels of copper can cause nausea, vomiting, diarrhea, headache, dizziness, and respiratory difficulty. (R514, R520) |
| Treatment | Not Available |
| References | |
| General References |
|
Targets
1. Alpha-synuclein
May be involved in the regulation of dopamine release and transport. Induces fibrillization of microtubule-associated protein tau. Reduces neuronal responsiveness to various apoptotic stimuli, leading to a decreased caspase-3 activation.
Copper binds to alpha-synuclein, initiating protein aggregation and likely contributing to the development of the neurodegenerative disorders Parkinson's disease and Alzheimer's disease. (R524)UniProt ID: P37840
Gene: SNCA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R524 — Davies P, Fontaine SN, Moualla D, Wang X, Wright JA, Brown DR: Amyloidogenic metal-binding proteins: new investigative pathways. Biochem Soc Trans. 2008 Dec;36(Pt 6):1299-303.
[19021544 ]
2. Amyloid beta A4 protein
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1. Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with Also bind GPC1 in lipid rafts. Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain (By similarity). The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis. N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).
Copper binds the N-terminal region of amyloid precursor protein, promoting the generation of β-amyloid from the protein. This is believed to contribute to the development of the neurodegenerative disorders Parkinson's disease and Alzheimer's disease. (R524)UniProt ID: P05067
Gene: APP
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R524 — Davies P, Fontaine SN, Moualla D, Wang X, Wright JA, Brown DR: Amyloidogenic metal-binding proteins: new investigative pathways. Biochem Soc Trans. 2008 Dec;36(Pt 6):1299-303.
[19021544 ]
3. Glutathione reductase, mitochondrial
Maintains high levels of reduced glutathione in the cytosol.
Excess copper is sequestered within hepatocyte lysosomes, where it is complexed with metallothionein. Copper hepatotoxicity is believed to occur when the lysosomes become saturated and copper accumulates in the nucleus, causing nuclear damage. This damage is possibly a result of oxidative damage, including lipid peroxidation. Copper inhibits the sulfhydryl group enzymes such as glucose-6-phosphate 1-dehydrogenase, glutathione reductase, and paraoxonases, which protect the cell from free oxygen radicals. It also influences gene expression and is a co-factor for oxidative enzymes such as cytochrome C oxidase and lysyl oxidase. In addition, the oxidative stress induced by copper is thought to activate acid sphingomyelinase, which lead to the production of ceramide, an apoptotic signal, as well as cause hemolytic anemia. (R513, R523, R525, R526)UniProt ID: P00390
Gene: GSR
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R513 — Wikipedia. Copper. Last Updated 29 May 2009. [Link]
- R523 — Baxter PJ, Adams PH, & Aw TC (2000). Hunter's Diseases of Occupations. 9th ed. New York, NY: Oxford University Press Inc.
- R525 — Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23.
[17697726 ]
- R526 — US Environmental Protection Agency (2008). Drinking Water Health Advisory for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene. [Link]
4. Serum paraoxonase/arylesterase 1
Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic acid esters. Mediates an enzymatic protection of low density lipoproteins against oxidative modification and the consequent series of events leading to atheroma formation.
Excess copper is sequestered within hepatocyte lysosomes, where it is complexed with metallothionein. Copper hepatotoxicity is believed to occur when the lysosomes become saturated and copper accumulates in the nucleus, causing nuclear damage. This damage is possibly a result of oxidative damage, including lipid peroxidation. Copper inhibits the sulfhydryl group enzymes such as glucose-6-phosphate 1-dehydrogenase, glutathione reductase, and paraoxonases, which protect the cell from free oxygen radicals. It also influences gene expression and is a co-factor for oxidative enzymes such as cytochrome C oxidase and lysyl oxidase. In addition, the oxidative stress induced by copper is thought to activate acid sphingomyelinase, which lead to the production of ceramide, an apoptotic signal, as well as cause hemolytic anemia. (R513, R523, R525, R526)UniProt ID: P27169
Gene: PON1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R513 — Wikipedia. Copper. Last Updated 29 May 2009. [Link]
- R523 — Baxter PJ, Adams PH, & Aw TC (2000). Hunter's Diseases of Occupations. 9th ed. New York, NY: Oxford University Press Inc.
- R525 — Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23.
[17697726 ]
- R526 — US Environmental Protection Agency (2008). Drinking Water Health Advisory for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene. [Link]
5. Glucose-6-phosphate 1-dehydrogenase
Produces pentose sugars for nucleic acid synthesis and main producer of NADPH reducing power.
Excess copper is sequestered within hepatocyte lysosomes, where it is complexed with metallothionein. Copper hepatotoxicity is believed to occur when the lysosomes become saturated and copper accumulates in the nucleus, causing nuclear damage. This damage is possibly a result of oxidative damage, including lipid peroxidation. Copper inhibits the sulfhydryl group enzymes such as glucose-6-phosphate 1-dehydrogenase, glutathione reductase, and paraoxonases, which protect the cell from free oxygen radicals. It also influences gene expression and is a co-factor for oxidative enzymes such as cytochrome C oxidase and lysyl oxidase. In addition, the oxidative stress induced by copper is thought to activate acid sphingomyelinase, which lead to the production of ceramide, an apoptotic signal, as well as cause hemolytic anemia. (R513, R523, R525, R526)UniProt ID: P11413
Gene: G6PD
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R513 — Wikipedia. Copper. Last Updated 29 May 2009. [Link]
- R523 — Baxter PJ, Adams PH, & Aw TC (2000). Hunter's Diseases of Occupations. 9th ed. New York, NY: Oxford University Press Inc.
- R525 — Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23.
[17697726 ]
- R526 — US Environmental Protection Agency (2008). Drinking Water Health Advisory for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene. [Link]
6. Serum paraoxonase/lactonase 3
Has low activity towards the organophosphate paraxon and aromatic carboxylic acid esters. Rapidly hydrolyzes lactones such as statin prodrugs (e.g. lovastatin). Hydrolyzes aromatic lactones and 5- or 6-member ring lactones with aliphatic substituents but not simple lactones or those with polar substituents.
Excess copper is sequestered within hepatocyte lysosomes, where it is complexed with metallothionein. Copper hepatotoxicity is believed to occur when the lysosomes become saturated and copper accumulates in the nucleus, causing nuclear damage. This damage is possibly a result of oxidative damage, including lipid peroxidation. Copper inhibits the sulfhydryl group enzymes such as glucose-6-phosphate 1-dehydrogenase, glutathione reductase, and paraoxonases, which protect the cell from free oxygen radicals. It also influences gene expression and is a co-factor for oxidative enzymes such as cytochrome C oxidase and lysyl oxidase. In addition, the oxidative stress induced by copper is thought to activate acid sphingomyelinase, which lead to the production of ceramide, an apoptotic signal, as well as cause hemolytic anemia. (R513, R523, R525, R526)UniProt ID: Q15166
Gene: PON3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- R513 — Wikipedia. Copper. Last Updated 29 May 2009. [Link]
- R523 — Baxter PJ, Adams PH, & Aw TC (2000). Hunter's Diseases of Occupations. 9th ed. New York, NY: Oxford University Press Inc.
- R525 — Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23.
[17697726 ]
- R526 — US Environmental Protection Agency (2008). Drinking Water Health Advisory for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene. [Link]