Copper is essential for human physiology
Copper serves as a co-founder of enzymes that are critically involved in breathing (cytochrome C oxidase), activation of neuroendocrine peptides (peptidyl-α-monoxigenase), pigmentation (tyrosinase), catecholamine synthesis and purification (dopamine, β-monooxigenase), radical defense (dysmonic superoxide [sod], sod1 and sod3) and many other cellular processes. In the blood, the ceruloplasmin, the main protein that transports copper, contains six atoms of molecule (holoceruplasmin), but it can be present as the protein without copper (apoceruloplasmin).
Normal consumption in diet and copper absorption, contributed mainly by legumes, potatoes, nuts and seeds, chocolate, beef, viscera and seafood, normally exceed metabolic demand and appropriate levels are controlled by regulating excretioncopper biliary. However, these homeostatic mechanisms are affected in Wilson’s disease.
Copper balance is normally maintained by a protein network, which includes transmembrane copper transporters, cytosolic copper carrier proteins, copper storage molecules (metallotolateins) and enzymes that require copper. In addition, proteins that do not bind directly to copper, but regulate the abundance or activity of copper union / transport proteins also contribute to the homeostasis of cell copper. This regulatory network includes adapter proteins, kinases, components of cell traffic machinery, as well as DNA and RNA binding proteins. The mechanisms that regulate copper homeostasis are specific to cells and cells of cell. However, the same core protein set regulates copper homeostasis in most cells.
Copper enters mainly cells through the Copper Transport of High Affinity 1 (CTR1). Copper chaperones, for example, Copper Chaperon for Superoxide Dismut. ATP7A and ATP7B transport copper to the trans-golgi network for subsequent incorporation in copper-dependent enzymes and cell membrane for copper excretion that is present in excess.
Liver hepatocytes are the site of two important physiological processes that involve copper: first, ATP7B provides copper for incorporation into apoceruloplasmine for functional ceruloplasmin synthesis;Second, ATP7B facilitates the biliary copper excretion process. The inactivation of ATP7A (the gene associated with the disease of cerebral copper deficiency, or Menkes disease) or ATP7B produces a marked copper unbalance, next to the inactivation of specific copper dependent enzymes, and is clinically manifested as Menkes or WD, respectively. In addition, Mednik syndrome (mental retardation, enteropathy, deafness, neuropathy, ichthiosis and keratodermia) is caused by mutations in the gene of an adapter protein that participates in the intracellular traffic of ATP7A and ATP7B .
Mitochondria use cell copper for breathing and are also key regulators of cell copper balance. It is not clear how copper is distributed between cytolic copper proteins and copper binding proteins in mitochondria. A model suggests that a gradient of protein-co-binding affinities and, presumably, the relative abundance of proteins regulates copper division between cytosolic proteins. Inhibitory mutations in SCO1 and SCO2 proteins, which facilitate the incorporation of copper into cytochrome C oxidase, result in mitochondrial dysfunction and cell homeostasis of altered copper. The knowledge of the homeostatic copper network in general continues to expand, and its connection with numerous cellular processes becomes increasingly evident.
Recently, new functions for copper have been discovered in normal physiological processes and in the disease of the disease. For example, it has become clear that copper imbalance is a factor that contributes to lipid homeostatic instability . Abnormal lipid metabolism associated with a copper overload or deficiency is commonly observed in disorders such as WD, NAFLD and Diabetes. In addition, important physiological processes, such as the assembly of quilomicrones, angiogenesis, the myelinization of neurons, the healing of the wounds and the immune response depend on the homeostasis of copper. The role of copper in cell proliferation and angiogenesis is finding its first applications in clinical practice such as the agent of copper protein (tetratiomolibdato), it is being evaluated in cancer patients.
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