Copper (T3D0128)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (20)XML
Targets (20)
Record Information
Version2.0
Creation Date2009-03-06 18:58:08 UTC
Update Date2014-12-24 20:21:10 UTC
Accession NumberT3D0128
Identification
Common NameCopper
ClassSmall Molecule
DescriptionCopper is an essential nutrient to all higher plants and animals. Physiologically, it exists as an ion in the body. In animals, it is found primarily in the bloodstream, as a cofactor in various enzymes, and in copper-based pigments. In the body, copper shifts between the cuprous (Cu1+) and cupric (Cu2+) forms, though the majority of the body's copper is in the Cu2+ form. The ability of copper to easily accept and donate electrons explains its important role in oxidation-reduction (redox) reactions and in scavenging free radicals. Copper is a critical functional component of a number of essential enzymes known as cuproenzymes. For instance, the copper-dependent enzyme, cytochrome c oxidase, plays a critical role in cellular energy production. By catalyzing the reduction of molecular oxygen (O2) to water (H2O), cytochrome c oxidase generates an electrical gradient used by the mitochondria to create the vital energy-storing molecule, ATP. Another cuproenzyme, lysyl oxidase, is required for the cross-linking of collagen and elastin, which are essential for the formation of strong and flexible connective tissue. Another cuproeznyme, Monoamine oxidase (MAO), plays a role in the metabolism of the neurotransmitters norepinephrine, epinephrine, and dopamine. MAO also functions in the degradation of the neurotransmitter serotonin, which is the basis for the use of MAO inhibitors as antidepressants. One of the most important cuproenzymes is Superoxide dismutase (SOD). SOD functions as an antioxidant by catalyzing the conversion of superoxide radicals (free radicals or ROS) to hydrogen peroxide, which can subsequently be reduced to water by other antioxidant enzymes. Two forms of SOD contain copper: 1) copper/zinc SOD is found within most cells of the body, including red blood cells, and 2) extracellular SOD is a copper-containing enzyme found at high levels in the lungs and low levels in blood plasma. In sufficient amounts, copper can be poisonous or even fatal to organisms. Copper is normally bound to cuproenzymes (such as SOD, MOA) and is thus only toxic when unsequestered and unmediated. It is believed that zinc and copper compete for absorption in the digestive tract so that a diet that is excessive in one of these minerals may result in a deficiency in the other. An imbalance of zinc and copper status might be involved in human hypertension.
Compound Type
  • Copper Compound
  • Food Toxin
  • Household Toxin
  • Industrial/Workplace Toxin
  • Inorganic Compound
  • Metabolite
  • Metal
  • Natural Compound
  • Pollutant
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Copper ion
Copper(2+)
Copper(2+) ion
Copper(II)
Copper(II) cation
Copper(II) ion
Cu(2+)
Cu2+
Chemical FormulaCu
Average Molecular Mass63.545 g/mol
Monoisotopic Mass62.929 g/mol
CAS Registry Number7440-50-8
IUPAC Namecopper(2+) ion
Traditional Namecopper(2+) ion
SMILES[Cu++]
InChI IdentifierInChI=1S/Cu/q+2
InChI KeyInChIKey=JPVYNHNXODAKFH-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of inorganic compounds known as homogeneous transition metal compounds. These are inorganic compounds containing only metal atoms,with the largest atom being a transition metal atom.
KingdomInorganic compounds
Super ClassHomogeneous metal compounds
ClassHomogeneous transition metal compounds
Sub ClassNot Available
Direct ParentHomogeneous transition metal compounds
Alternative ParentsNot Available
Substituents
  • Homogeneous transition metal
Molecular FrameworkNot Available
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Brain
  • Erythrocyte
  • Hair
  • Intestine
  • Kidney
  • Liver
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceReddish metallic solid.
Experimental Properties
PropertyValue
Melting Point1083°C
Boiling Point2595°C (4703°F)
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
logP0.16ChemAxon
pKa (Strongest Acidic)3.09ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity0 m³·mol⁻¹ChemAxon
Polarizability1.78 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-9000000000-59c652eccc13cc365f652016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-9000000000-59c652eccc13cc365f652016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03di-9000000000-59c652eccc13cc365f652016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-9000000000-9acd78ab9faeb89677a72016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03di-9000000000-9acd78ab9faeb89677a72016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-03di-9000000000-9acd78ab9faeb89677a72016-08-03View Spectrum
Toxicity Profile
Route of ExposureOral (27) ; inhalation (27) ; dermal (27)
Mechanism of ToxicityExcess 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. (27, 25, 1, 30)
MetabolismCopper 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. (27, 29)
Toxicity ValuesLD50: 3500 ug/kg (Intraperitoneal, Mouse) (24)
Lethal Dose10 to 20 grams for an adult human. (23)
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesCopper 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. (27, 28)
Minimum Risk LevelAcute Oral: 0.01 mg/kg/day (26) Intermediate Oral: 0.01 mg/kg/day (26)
Health EffectsCopper toxicity, also called copperiedus, refers to the consequences of an excess of copper in the body. Copperiedus can occur from eating acid foods cooked in uncoated copper cookware, or from exposure to excess copper in drinking water or other environmental sources. Very-high doses of copper can damage liver and kidneys, and can even cause death. Copper may induce allergic responses in sensitive individuals. (28, 29)
SymptomsBreathing high levels of copper can cause irritation of the nose and throat. Acute symptoms of copper poisoning by ingestion include vomiting, hematemesis (vomiting of blood), hypotension (low blood pressure), melena (black "tarry" feces), coma, jaundice (yellowish pigmentation of the skin), and gastrointestinal distress. Individuals with glucose-6-phosphate deficiency may be at increased risk of hematologic effects of copper. Hemolytic anemia resulting from the treatment of burns with copper compounds is infrequent. Chronic (long-term) effects of copper exposure can damage the liver and kidneys.
TreatmentIn cases of suspected copper poisoning, penicillamine is the drug of choice, and dimercaprol, a heavy metal chelating agent, is often administered. Vinegar is not recommended, as it assists in solubilizing insoluble copper salts.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB00657
PubChem Compound ID23978
ChEMBL IDNot Available
ChemSpider ID25221
KEGG IDC00070
UniProt IDNot Available
OMIM ID121270147450215600309400602268603085603088603735603864607238610101
ChEBI ID30052
BioCyc IDCUCL2
CTD IDD003300
Stitch IDCopper
PDB IDCU
ACToR ID6411
Wikipedia LinkCopper
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23. [17697726 ]
  2. Bardsley PA, Howard P, DeBacker W, Vermeire P, Mairesse M, Ledent C, Radermecker M, Bury T, Ansquer J: Two years treatment with almitrine bismesylate in patients with hypoxic chronic obstructive airways disease. Eur Respir J. 1991 Mar;4(3):308-10. [1907566 ]
  3. Koury JC, de Olilveria AV Jr, Portella ES, de Olilveria CF, Lopes GC, Donangelo CM: Zinc and copper biochemical indices of antioxidant status in elite athletes of different modalities. Int J Sport Nutr Exerc Metab. 2004 Jun;14(3):358-72. [15256695 ]
  4. Hoogenraad TU: Paradigm shift in treatment of Wilson's disease: zinc therapy now treatment of choice. Brain Dev. 2006 Apr;28(3):141-6. Epub 2006 Feb 7. [16466879 ]
  5. Kedzierska E: [Concentrations of selected bioelements and toxic metals and their influence on health status of children and youth residing in Szczecin]. Ann Acad Med Stetin. 2003;49:131-43. [15552844 ]
  6. Dib N, Valsesia E, Malinge MC, Mauras Y, Misrahi M, Cales P: Late onset of Wilson's disease in a family with genetic haemochromatosis. Eur J Gastroenterol Hepatol. 2006 Jan;18(1):43-7. [16357618 ]
  7. Kodama H, Sato E, Gu YH, Shiga K, Fujisawa C, Kozuma T: Effect of copper and diethyldithiocarbamate combination therapy on the macular mouse, an animal model of Menkes disease. J Inherit Metab Dis. 2005;28(6):971-8. [16435190 ]
  8. Cengiz B, Soylemez F, Ozturk E, Cavdar AO: Serum zinc, selenium, copper, and lead levels in women with second-trimester induced abortion resulting from neural tube defects: a preliminary study. Biol Trace Elem Res. 2004 Mar;97(3):225-35. [14997023 ]
  9. Langner C, Denk H: Wilson disease. Virchows Arch. 2004 Aug;445(2):111-8. Epub 2004 Jun 17. [15205951 ]
  10. Kitzberger R, Madl C, Ferenci P: Wilson disease. Metab Brain Dis. 2005 Dec;20(4):295-302. [16382340 ]
  11. Chen D, Cui QC, Yang H, Dou QP: Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity. Cancer Res. 2006 Nov 1;66(21):10425-33. [17079463 ]
  12. Briviba K, Schnabele K, Rechkemmer G, Bub A: Supplementation of a diet low in carotenoids with tomato or carrot juice does not affect lipid peroxidation in plasma and feces of healthy men. J Nutr. 2004 May;134(5):1081-3. [15113949 ]
  13. Pizent A, Jurasovic J, Telisman S: Serum calcium, zinc, and copper in relation to biomarkers of lead and cadmium in men. J Trace Elem Med Biol. 2003;17(3):199-205. [14968933 ]
  14. Squitti R, Barbati G, Rossi L, Ventriglia M, Dal Forno G, Cesaretti S, Moffa F, Caridi I, Cassetta E, Pasqualetti P, Calabrese L, Lupoi D, Rossini PM: Excess of nonceruloplasmin serum copper in AD correlates with MMSE, CSF [beta]-amyloid, and h-tau. Neurology. 2006 Jul 11;67(1):76-82. [16832081 ]
  15. Odland JO, Nieboer E, Romanova N, Thomassen Y: Elements in placenta and pregnancy outcome in arctic and subarctic areas. Int J Circumpolar Health. 2004 May;63(2):169-87. [15253483 ]
  16. Venelinov TI, Davies IM, Beattie JH: Dialysis-Chelex method for determination of exchangeable copper in human plasma. Anal Bioanal Chem. 2004 Jul;379(5-6):777-80. Epub 2004 Feb 26. [14991216 ]
  17. Attri S, Sharma N, Jahagirdar S, Thapa BR, Prasad R: Erythrocyte metabolism and antioxidant status of patients with Wilson disease with hemolytic anemia. Pediatr Res. 2006 Apr;59(4 Pt 1):593-7. [16549536 ]
  18. Jablonska-Kaszewska I, Dabrowska E, Drobinska Jurowiecka A, Falkiewicz B: Treatment of Wilson's disease. Med Sci Monit. 2003 Aug;9 Suppl 3:5-8. [15156602 ]
  19. Daniel KG, Harbach RH, Guida WC, Dou QP: Copper storage diseases: Menkes, Wilsons, and cancer. Front Biosci. 2004 Sep 1;9:2652-62. [15358588 ]
  20. Aoki T: [Genetic disorders of copper transport--diagnosis and new treatment for the patients of Wilson's disease]. No To Hattatsu. 2005 Mar;37(2):99-109. [15773321 ]
  21. Meng Y, Miyoshi I, Hirabayashi M, Su M, Mototani Y, Okamura T, Terada K, Ueda M, Enomoto K, Sugiyama T, Kasai N: Restoration of copper metabolism and rescue of hepatic abnormalities in LEC rats, an animal model of Wilson disease, by expression of human ATP7B gene. Biochim Biophys Acta. 2004 Nov 5;1690(3):208-19. [15511628 ]
  22. Gorter RW, Butorac M, Cobian EP: Examination of the cutaneous absorption of copper after the use of copper-containing ointments. Am J Ther. 2004 Nov-Dec;11(6):453-8. [15543084 ]
  23. Baselt RC (2000). Disposition of Toxic Drugs and Chemicals in Man, 5th ed. Foster City, CA: Chemical Toxicology Institute.
  24. National Institute for Occupational Safety and Health (2002). RTECS: Registry of Toxic Effects of Chemical Substances.
  25. Baxter PJ, Adams PH, & Aw TC (2000). Hunter's Diseases of Occupations. 9th ed. New York, NY: Oxford University Press Inc.
  26. ATSDR - Agency for Toxic Substances and Disease Registry (2001). Minimal Risk Levels (MRLs) for Hazardous Substances. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  27. Wikipedia. Copper. Last Updated 29 May 2009. [Link]
  28. ATSDR - Agency for Toxic Substances and Disease Registry (2004). Toxicological profile for copper. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  29. International Programme on Chemical Safety (IPCS) INCHEM (1998). Environmental Health Criteria for Copper. [Link]
  30. US Environmental Protection Agency (2008). Drinking Water Health Advisory for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

Target Details
1. Major prion protein
General Function:
Tubulin binding
Specific Function:
Its primary physiological function is unclear. Has cytoprotective activity against internal or environmental stresses. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro) (PubMed:12732622, PubMed:19936054, PubMed:20564047). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity).
Gene Name:
PRNP
Uniprot ID:
P04156
Molecular Weight:
27661.21 Da
References
  1. Wells MA, Jackson GS, Jones S, Hosszu LL, Craven CJ, Clarke AR, Collinge J, Waltho JP: A reassessment of copper(II) binding in the full-length prion protein. Biochem J. 2006 Nov 1;399(3):435-44. [16824036 ]
  2. Merle U, Stremmel W, Gessner R: Influence of homozygosity for methionine at codon 129 of the human prion gene on the onset of neurological and hepatic symptoms in Wilson disease. Arch Neurol. 2006 Jul;63(7):982-5. [16831968 ]
  3. Shiraishi N, Utsunomiya H, Nishikimi M: Combination of NADPH and copper ions generates proteinase K-resistant aggregates from recombinant prion protein. J Biol Chem. 2006 Nov 17;281(46):34880-7. Epub 2006 Sep 21. [16990274 ]
  4. Shearer J, Soh P: Ni K-edge XAS suggests that coordination of Ni(II) to the unstructured amyloidogenic region of the human prion protein produces a Ni(2) bis-mu-hydroxo dimer. J Inorg Biochem. 2007 Feb;101(2):370-3. Epub 2006 Oct 20. [17126907 ]
  5. Shearer J, Soh P: The copper(II) adduct of the unstructured region of the amyloidogenic fragment derived from the human prion protein is redox-active at physiological pH. Inorg Chem. 2007 Feb 5;46(3):710-9. [17257012 ]
  6. Valensin G, Molteni E, Valensin D, Taraszkiewicz M, Kozlowski H: Molecular dynamics study of the Cu2+ binding-induced "structuring" of the N-terminal domain of human prion protein. J Phys Chem B. 2009 Mar 19;113(11):3277-9. doi: 10.1021/jp901030a. [19236027 ]
  7. Pushie MJ, Vogel HJ: A potential mechanism for Cu2+ reduction, beta-cleavage, and beta-sheet initiation within the N-terminal domain of the prion protein: insights from density functional theory and molecular dynamics calculations. J Toxicol Environ Health A. 2009;72(17-18):1040-59. doi: 10.1080/15287390903084389. [19697239 ]
Target Details
2. Metallothionein-3
General Function:
Zinc ion binding
Specific Function:
Binds heavy metals. Contains three zinc and three copper atoms per polypeptide chain and only a negligible amount of cadmium. Inhibits survival and neurite formation of cortical neurons in vitro.
Gene Name:
MT3
Uniprot ID:
P25713
Molecular Weight:
6926.855 Da
References
  1. Roschitzki B, Vasak M: A distinct Cu(4)-thiolate cluster of human metallothionein-3 is located in the N-terminal domain. J Biol Inorg Chem. 2002 Jun;7(6):611-6. Epub 2002 Feb 7. [12072966 ]
  2. Roschitzki B, Vasak M: Redox labile site in a Zn4 cluster of Cu4,Zn4-metallothionein-3. Biochemistry. 2003 Aug 19;42(32):9822-8. [12911326 ]
  3. Zheng WJ, Wu F, Zhuang HQ, Lu C, Yang F, Ma WL, Hua ZC: Expression of human metallothionein III and its metalloabsorption capability in Escherichia coli. Prep Biochem Biotechnol. 2004 Aug;34(3):265-78. [15461142 ]
  4. Toriumi S, Saito T, Hosokawa T, Takahashi Y, Numata T, Kurasaki M: Metal binding ability of metallothionein-3 expressed in Escherichia coli. Basic Clin Pharmacol Toxicol. 2005 Apr;96(4):295-301. [15755312 ]
  5. Kameo S, Nakai K, Kurokawa N, Kanehisa T, Naganuma A, Satoh H: Metal components analysis of metallothionein-III in the brain sections of metallothionein-I and metallothionein-II null mice exposed to mercury vapor with HPLC/ICP-MS. Anal Bioanal Chem. 2005 Apr;381(8):1514-9. Epub 2005 Mar 22. [15782327 ]
Target Details
3. Glucose-6-phosphate 1-dehydrogenase
General Function:
Protein homodimerization activity
Specific Function:
Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis. The main function of this enzyme is to provide reducing power (NADPH) and pentose phosphates for fatty acid and nucleic acid synthesis.
Gene Name:
G6PD
Uniprot ID:
P11413
Molecular Weight:
59256.31 Da
References
  1. Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23. [17697726 ]
  2. Baxter PJ, Adams PH, & Aw TC (2000). Hunter's Diseases of Occupations. 9th ed. New York, NY: Oxford University Press Inc.
  3. Wikipedia. Copper. Last Updated 29 May 2009. [Link]
  4. US Environmental Protection Agency (2008). Drinking Water Health Advisory for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene. [Link]
Target Details
4. Glutathione reductase, mitochondrial
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
References
  1. Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23. [17697726 ]
  2. Baxter PJ, Adams PH, & Aw TC (2000). Hunter's Diseases of Occupations. 9th ed. New York, NY: Oxford University Press Inc.
  3. Wikipedia. Copper. Last Updated 29 May 2009. [Link]
  4. US Environmental Protection Agency (2008). Drinking Water Health Advisory for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene. [Link]
Target Details
5. Serum paraoxonase/arylesterase 1
General Function:
Protein homodimerization activity
Specific Function:
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.
Gene Name:
PON1
Uniprot ID:
P27169
Molecular Weight:
39730.99 Da
References
  1. Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23. [17697726 ]
  2. Baxter PJ, Adams PH, & Aw TC (2000). Hunter's Diseases of Occupations. 9th ed. New York, NY: Oxford University Press Inc.
  3. Wikipedia. Copper. Last Updated 29 May 2009. [Link]
  4. US Environmental Protection Agency (2008). Drinking Water Health Advisory for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene. [Link]
Target Details
6. Serum paraoxonase/lactonase 3
General Function:
Protein homodimerization activity
Specific Function:
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.
Gene Name:
PON3
Uniprot ID:
Q15166
Molecular Weight:
39607.185 Da
References
  1. Brewer GJ: A brand new mechanism for copper toxicity. J Hepatol. 2007 Oct;47(4):621-2. Epub 2007 Jul 23. [17697726 ]
  2. Baxter PJ, Adams PH, & Aw TC (2000). Hunter's Diseases of Occupations. 9th ed. New York, NY: Oxford University Press Inc.
  3. Wikipedia. Copper. Last Updated 29 May 2009. [Link]
  4. US Environmental Protection Agency (2008). Drinking Water Health Advisory for 2,4-Dinitrotoluene and 2,6-Dinitrotoluene. [Link]
Target Details
7. Amyloid beta A4 protein
General Function:
Transition metal ion binding
Specific Function:
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).
Gene Name:
APP
Uniprot ID:
P05067
Molecular Weight:
86942.715 Da
References
  1. 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. doi: 10.1042/BST0361299. [19021544 ]
  2. Adlard PA, Bush AI: Metals and Alzheimer's disease. J Alzheimers Dis. 2006 Nov;10(2-3):145-63. [17119284 ]
  3. Kong GK, Adams JJ, Harris HH, Boas JF, Curtain CC, Galatis D, Masters CL, Barnham KJ, McKinstry WJ, Cappai R, Parker MW: Structural studies of the Alzheimer's amyloid precursor protein copper-binding domain reveal how it binds copper ions. J Mol Biol. 2007 Mar 16;367(1):148-61. Epub 2006 Dec 21. [17239395 ]
Target Details
8. Copper-transporting ATPase 2
General Function:
Copper-exporting atpase activity
Specific Function:
Involved in the export of copper out of the cells, such as the efflux of hepatic copper into the bile.
Gene Name:
ATP7B
Uniprot ID:
P35670
Molecular Weight:
157261.34 Da
References
  1. Bunce J, Achila D, Hetrick E, Lesley L, Huffman DL: Copper transfer studies between the N-terminal copper binding domains one and four of human Wilson protein. Biochim Biophys Acta. 2006 Jun;1760(6):907-12. Epub 2006 Mar 3. [16632204 ]
  2. Cater MA, La Fontaine S, Mercer JF: Copper binding to the N-terminal metal-binding sites or the CPC motif is not essential for copper-induced trafficking of the human Wilson protein (ATP7B). Biochem J. 2007 Jan 1;401(1):143-53. [16939419 ]
  3. Niemiec MS, Weise CF, Wittung-Stafshede P: In vitro thermodynamic dissection of human copper transfer from chaperone to target protein. PLoS One. 2012;7(5):e36102. doi: 10.1371/journal.pone.0036102. Epub 2012 May 4. [22574136 ]
Target Details
9. Copper chaperone for superoxide dismutase
General Function:
Zinc ion binding
Specific Function:
Delivers copper to copper zinc superoxide dismutase (SOD1).
Gene Name:
CCS
Uniprot ID:
O14618
Molecular Weight:
29040.445 Da
References
  1. Stasser JP, Eisses JF, Barry AN, Kaplan JH, Blackburn NJ: Cysteine-to-serine mutants of the human copper chaperone for superoxide dismutase reveal a copper cluster at a domain III dimer interface. Biochemistry. 2005 Mar 8;44(9):3143-52. [15736924 ]
  2. Wright GS, Hasnain SS, Grossmann JG: The structural plasticity of the human copper chaperone for SOD1: insights from combined size-exclusion chromatographic and solution X-ray scattering studies. Biochem J. 2011 Oct 1;439(1):39-44. doi: 10.1042/BJ20110948. [21722094 ]
Target Details
10. Copper transport protein ATOX1
General Function:
Metallochaperone activity
Specific Function:
Binds and deliver cytosolic copper to the copper ATPase proteins. May be important in cellular antioxidant defense.
Gene Name:
ATOX1
Uniprot ID:
O00244
Molecular Weight:
7401.575 Da
References
  1. Banci L, Bertini I, Cantini F, DellaMalva N, Herrmann T, Rosato A, Wuthrich K: Solution structure and intermolecular interactions of the third metal-binding domain of ATP7A, the Menkes disease protein. J Biol Chem. 2006 Sep 29;281(39):29141-7. Epub 2006 Jul 26. [16873374 ]
  2. Niemiec MS, Weise CF, Wittung-Stafshede P: In vitro thermodynamic dissection of human copper transfer from chaperone to target protein. PLoS One. 2012;7(5):e36102. doi: 10.1371/journal.pone.0036102. Epub 2012 May 4. [22574136 ]
Target Details
11. Alpha-synuclein
General Function:
Not Available
Specific Function:
Not Available
Gene Name:
SNCA
Uniprot ID:
P37840
Molecular Weight:
14460.155 Da
References
  1. 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. doi: 10.1042/BST0361299. [19021544 ]
Target Details
12. Beta-2 adrenergic receptor
General Function:
Protein homodimerization activity
Specific Function:
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine.
Gene Name:
ADRB2
Uniprot ID:
P07550
Molecular Weight:
46458.32 Da
References
  1. Elling CE, Frimurer TM, Gerlach LO, Jorgensen R, Holst B, Schwartz TW: Metal ion site engineering indicates a global toggle switch model for seven-transmembrane receptor activation. J Biol Chem. 2006 Jun 23;281(25):17337-46. Epub 2006 Mar 27. [16567806 ]
Target Details
13. Ceruloplasmin
General Function:
Ferroxidase activity
Specific Function:
Ceruloplasmin is a blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron transport across the cell membrane. Provides Cu(2+) ions for the ascorbate-mediated deaminase degradation of the heparan sulfate chains of GPC1. May also play a role in fetal lung development or pulmonary antioxidant defense (By similarity).
Gene Name:
CP
Uniprot ID:
P00450
Molecular Weight:
122204.45 Da
References
  1. Bento I, Peixoto C, Zaitsev VN, Lindley PF: Ceruloplasmin revisited: structural and functional roles of various metal cation-binding sites. Acta Crystallogr D Biol Crystallogr. 2007 Feb;63(Pt 2):240-8. Epub 2007 Jan 16. [17242517 ]
Target Details
14. Copper-transporting ATPase 1
General Function:
Superoxide dismutase copper chaperone activity
Specific Function:
May supply copper to copper-requiring proteins within the secretory pathway, when localized in the trans-Golgi network. Under conditions of elevated extracellular copper, it relocalized to the plasma membrane where it functions in the efflux of copper from cells.
Gene Name:
ATP7A
Uniprot ID:
Q04656
Molecular Weight:
163372.275 Da
References
  1. Banci L, Bertini I, Cantini F, DellaMalva N, Herrmann T, Rosato A, Wuthrich K: Solution structure and intermolecular interactions of the third metal-binding domain of ATP7A, the Menkes disease protein. J Biol Chem. 2006 Sep 29;281(39):29141-7. Epub 2006 Jul 26. [16873374 ]
Target Details
15. Endonuclease 8-like 1
General Function:
Not Available
Specific Function:
Not Available
Gene Name:
NEIL1
Uniprot ID:
Q96FI4
Molecular Weight:
43683.625 Da
References
  1. Hegde ML, Hegde PM, Holthauzen LM, Hazra TK, Rao KS, Mitra S: Specific Inhibition of NEIL-initiated repair of oxidized base damage in human genome by copper and iron: potential etiological linkage to neurodegenerative diseases. J Biol Chem. 2010 Sep 10;285(37):28812-25. doi: 10.1074/jbc.M110.126664. Epub 2010 Jul 9. [20622253 ]
Target Details
16. Endonuclease 8-like 2
General Function:
Zinc ion binding
Specific Function:
Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Has DNA glycosylase activity towards 5-hydroxyuracil and other oxidized derivatives of cytosine with a preference for mismatched double-stranded DNA (DNA bubbles). Has low or no DNA glycosylase activity towards thymine glycol, 2-hydroxyadenine, hypoxanthine and 8-oxoguanine. Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates.
Gene Name:
NEIL2
Uniprot ID:
Q969S2
Molecular Weight:
36826.285 Da
References
  1. Hegde ML, Hegde PM, Holthauzen LM, Hazra TK, Rao KS, Mitra S: Specific Inhibition of NEIL-initiated repair of oxidized base damage in human genome by copper and iron: potential etiological linkage to neurodegenerative diseases. J Biol Chem. 2010 Sep 10;285(37):28812-25. doi: 10.1074/jbc.M110.126664. Epub 2010 Jul 9. [20622253 ]
Target Details
17. Fas-binding factor 1
General Function:
Not Available
Specific Function:
Keratin-binding protein required for epithelial cell polarization. Involved in apical junction complex (AJC) assembly via its interaction with PARD3. Required for ciliogenesis.
Gene Name:
FBF1
Uniprot ID:
Q8TES7
Molecular Weight:
125445.19 Da
References
  1. Mothes E, Faller P: Evidence that the principal CoII-binding site in human serum albumin is not at the N-terminus: implication on the albumin cobalt binding test for detecting myocardial ischemia. Biochemistry. 2007 Feb 27;46(8):2267-74. Epub 2007 Feb 3. [17274600 ]
Target Details
18. Hephaestin-like protein 1
General Function:
Ferroxidase activity
Specific Function:
May function as a ferroxidase and may be involved in copper transport and homeostasis.
Gene Name:
HEPHL1
Uniprot ID:
Q6MZM0
Molecular Weight:
131601.67 Da
References
  1. Chen H, Attieh ZK, Syed BA, Kuo YM, Stevens V, Fuqua BK, Andersen HS, Naylor CE, Evans RW, Gambling L, Danzeisen R, Bacouri-Haidar M, Usta J, Vulpe CD, McArdle HJ: Identification of zyklopen, a new member of the vertebrate multicopper ferroxidase family, and characterization in rodents and human cells. J Nutr. 2010 Oct;140(10):1728-35. doi: 10.3945/jn.109.117531. Epub 2010 Aug 4. [20685892 ]
Target Details
19. Protein SCO1 homolog, mitochondrial
General Function:
Copper ion binding
Specific Function:
Thought to play a role in cellular copper homeostasis, mitochondrial redox signaling or insertion of copper into the active site of COX.
Gene Name:
SCO1
Uniprot ID:
O75880
Molecular Weight:
33813.69 Da
References
  1. Banci L, Bertini I, Ciofi-Baffoni S, Leontari I, Martinelli M, Palumaa P, Sillard R, Wang S: Human Sco1 functional studies and pathological implications of the P174L mutant. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):15-20. Epub 2006 Dec 20. [17182746 ]
Target Details
20. Superoxide dismutase [Cu-Zn]
General Function:
Zinc ion binding
Specific Function:
Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
Gene Name:
SOD1
Uniprot ID:
P00441
Molecular Weight:
15935.685 Da
References
  1. Lapenna D, Ciofani G, Pierdomenico SD, Giamberardino MA, Cuccurullo F: Copper, zinc superoxide dismutase plus hydrogen peroxide: a catalytic system for human lipoprotein oxidation. FEBS Lett. 2005 Jan 3;579(1):245-50. [15620721 ]