Definition
A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.
Description
Copper 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.
Top Gene Interactions
Related Pathways
Copper Health Effects
General Information
- 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. (L277, L279)
- 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. (L277, L278)
- Health Effects: Copper 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. (L278, L279)
- Symptoms:
Breathing 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.
- Treatment:
In 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.
- Route of Exposure:
Oral (L277) ; inhalation (L277) ; dermal (L277)
Toxicity
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: 3500 ug/kg (Intraperitoneal, Mouse) (T26)
- Lethal Dose: 10 to 20 grams for an adult human. (T17)
- Minimum Risk Level: Acute Oral: 0.01 mg/kg/day (L134) Intermediate Oral: 0.01 mg/kg/day (L134)
Mechanism of Action
| Target Name | Mechanism of Action | References |
|---|---|---|
|
Superoxide dismutase [Cu-Zn] Major prion protein Beta-2 adrenergic receptor Copper-transporting ATPase 1 Metallothionein-3 Fas-binding factor 1 Ceruloplasmin Copper transport protein ATOX1 Copper-transporting ATPase 2 Copper chaperone for superoxide dismutase Hephaestin-like protein 1 Endonuclease 8-like 1 Endonuclease 8-like 2 Protein SCO1 homolog, mitochondrial |
20622253 12911326 16873374 15736924 17242517 12072966 15782327 17126907 16567806 22574136 19697239 20685892 15755312 16632204 16990274 17182746 15461142 19236027 15620721 16831968 17257012 21722094 16824036 17274600 16939419 |
|
| Amyloid beta A4 protein | 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. (A173) |
17239395 17119284 19021544 |
| Alpha-synuclein | 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. (A173) |
19021544 |
|
Glutathione reductase, mitochondrial Serum paraoxonase/arylesterase 1 Glucose-6-phosphate 1-dehydrogenase Serum paraoxonase/lactonase 3 |
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. (L277, T49, A174, L280) |
17697726 2008 2000 |