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Copper, Cu, Cu+, Cu2+, Cyprium

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Copper is considered as one of the essential trace element in the human body, animals and many plants. In the adult human body has between 75 and 150 mg of copper. More than half of the copper in the human body enters into the composition of muscle and bone. Its concentration is highest in the liver, brain, kidneys and heart.

Physiological role

Copper is an important component of many enzymes in the body and play an important role in cell energy production. Activity of these enzymes is highest in the heart, brain, liver and kidney.

In addition, enzymes that are responsible for connective tissue proteins formation (collagen and elastin) require copper. Copper is necessary for the development and maintenance of blood vessels, skin, bones and joints.

It helps in preserving cells of the nervous system. Also has a beneficial effect on osteoporosis (brittle bone disease due to lack of calcium).

Copper is involved in the release of iron from their depot, the creation of bone marrow and maturation of red blood cells.

Copper is an essential trace metal which plays a fundamental role in the biochemistry of the human nervous system. Copper is essential for the synthesis of phospholipids of cell membranes and thus maintain myelin that separates the nerve cell from the environment and regulates the levels of the neurotransmitters.

Copper is a component of the enzyme copper-zinc superoxide dismutase (Cu / Zn SOD), which serves as an antioxidant essential to preserve the body from damage caused by free radicals. Matching the copper and zinc is important for the normal functioning of the body.

Copper is very important in creating the immune response to infection. During the inflammatory process or infection, the mobilizations of the two compounds in their structure include ion copper superoxide dismutase and ceruloplasmin. Copper is also necessary for the maturation and function of T cells.

It also plays an important role in the contraction of the heart muscle, as well as in the healthy functioning of small blood vessels that control blood flow, nutrients and waste products. It affects the normal functioning of muscles and blood vessels involved in the lining of blood vessels.

Melanin (natural pigment located in the hair and skin) includes enzymes that contain copper. Enzyme histaminase that metabolizes the amino acid histamine, requires copper for its functioning. Copper is also involved in the metabolism of fat and cholesterol, as well as the normal functioning of insulin (which regulates the metabolism of sugar). Is involved in the synthesis of prostaglandins (substances that regulate many functions such as heart rate, blood pressure and wound healing).

Metabolism

For copper absorption from the gastrointestinal tract is required a specific mechanism because the copper ion (Cu2+) is practically insoluble. An unidentified low molecular weight substances from human saliva and gastric juice creates a complex with Cu2+, which is soluble in the pH of intestinal fluids. In the small intestine, copper is probably associated with the low molecular protein that binds metals, usually called metallothionein. Copper enters into the plasma where it binds to amino acids, especially histidine, and serum albumin. Copper is within an hour removed from the circulation by the liver.

Liver processes copper in two ways. The first is that copper is excreted via the bile in the gastrointestinal tract. The fact is that homeostasis of copper is maintained only this excretion in the bile. The more copper is excreted, the more is it in the feces. Normal urine has a trace quantity of copper.

Another way of copper metabolism in the liver is its implementation in ceruloplasmin, a glycoprotein which is synthesized only in the liver. Ceruloplasmin is a copper dependent protein. It contain about 95% of the total plasma copper. Ceruloplasmin is not a transport protein for Cu2+, because the copper in ceruloplasmin is not exchanged between the ions of copper and copper associated with other molecules. Ceruloplasmin contains 6-8 copper atoms, half of the cuprous (Cu+), and half of cupric (Cu2+) form.

Ceruloplasmin oxidizes Fe2+ to Fe3+ which is essential to the mechanism of absorption of iron from gastroinestinalnog tract. The other copper metalloproteins are cytochrome oxidase, tyrosinase, monoamine oxidase, superoxide dismutase and lysyl oxidase.

Food sources of copper

Its concentration is highest in the liver, kidney, heart, meat, shellfish, aronia, nuts and similar fruits, raisins, beans, peas, cereals, brewer's yeast, olive, sesame and chocolate.

Recommended daily allowance

Adults are recommended 2-3 mg per day (in the UK it is recommended to 1.2 mg).

Copper deficiency

Symptoms of deficiency: altered heart rate, hair loss, weakness.

Copper deficiency in infants affect slow growth, pale skin, anaemia, diarrhoea, lack of pigment in the hair and skin, bulging varicose veins.

Menkes disease (MNK, also called Menkes syndrome). The symptoms are stiff and brittle hair. This disorder is linked to the X chromosome, which leads to poor absorption of copper from the small intestine. In patients with this disease absorption and the transport of copper in the cells of the mucous membrane are normal. But the transport through the diaphragm of serous mucous cells, ie. third stage of transport is abnormal. When copper is added intravenously in children with the disease organism normally absorbed it. In this way, many severe symptoms of the disease (mental retardation, unstable body temperature, abnormal bone development and susceptibility to infections) may be prevented if you start treatment early enough.

In adults copper deficiency leads to anaemia, water retention in the body, weakening the walls of blood vessels, irritability, brittle bones, hair depigmentation, loss of quality.

People who consume a lot of dietary phytate, which binds copper in the intestine, then people who have impoverished diet, people with diarrhea for a long period of time and the people who bring large amounts of zinc, cadmium, fluoride and molybdenum are the highest risk for symptoms of copper deficiency.

Poor absorption of copper may occur in patients with rheumatoid arthritis.

Copper deficiency leads to reduced resistance to infection, since the activity of white blood cells and cellular immune response are reduced. The ratio of zinc and copper can also affect the efficiency of the immune response. Susceptibility to disease is likely to increase when there is a high intake of copper and low intake of zinc.

Overdose

Wilson's disease: Autosomal, recessive inborn defect of copper fitting into a new synthesized apoceruloplasmin wat is needed to be created ceruloplasmin. It is not known whether this is a genetic defect in the structural gene for ceruloplasmin or defect in the process of installing Cu2+ in ceruloplasmin. In addition, patients with this disease have a reduced ability of the liver to the biliary excretion of copper. Therefore, the body retains more copper. This particularly occurs in the liver, brain and kidneys. Since the patient's plasma ceruloplasmin doesn't contain Cu2+, the concentration of copper in serum is low. In these patients is therefore significantly increased copper excretion in the urine. These patients have no signs of abnormality in the absorption of iron, although we know that ceruloplasmin without copper cannot act as ferroxidase. Giving compounds that bind copper can reduce organ damage.

Copper toxicosis is rare, but can occur if the entries are more than 200 mg of copper per day. It can lead to nausea, vomiting, abdominal pain, diarrhea, muscle pain, abnormal mental status, headache and decreased immune response. The lethal dose of copper is about 3.5 gm. Unbalanced ratio of copper and zinc may be an important factor in copper poisoning.

In patients with ulcerative colitis the copper in the tissues can be increased and excess of it may aggravate the disease. High levels of copper can be causative of many heart diseases.

The symptoms of copper poisoning include blue and green diarrhoea, saliva, acute haemolysis and some renal function abnormalities.

Copper in medicine

Copper is used since ancient times for medicinal purposes, and is still used in many medicines to treat: After radiation treatment; Anaemia; Cardiovascular disorders; Cataracts; Cerebrovascular disorders; Diabetes; Diphtheria; Elasticity of the skin; Epilepsy; Fever; Hair; Headache; Infection; Inflammatory (aspirin, ibuprofen); Malignant tumours; Osteoarthritis; Osteoporosis; Reduction of pain; Rejuvenation of the body; Reumatidnog arthritis; Scarlet fever; Stress; Tuberculosis; Ulcers; Varicose veins; Wound healing

References

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Institute of Medicine (US) Panel on Micronutrients. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington (DC): National Academies Press (US); 2001. 7, Copper. [Web Reference]

Kornblatt A.P., Nicoletti V.G. and Travaglia A., 2016, “The neglected role of copper ions in wound healing,” Journal of Inorganic Biochemistry; 161(8): [Web Reference]

Malhotra V.K., 1998, “Biochemistry for Students. 10th Ed,” Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India. [Web Reference]

Soetan K.O., Olaiya C. O. and Oyewole O.E., 2010, “The importance of mineral elements for humans, domestic animals and plants-A review,” African Journal of Food Science; 4(5): 200-222. [Web Reference]

Wachnik A., 1988, “The physiological role of copper and the problems of copper nutritional deficiency,” Food/Nahrung; 32(8): 755-765. [Web Reference]

Waggoner D.J., Bartnikas T.B. and Gitlin J.D., 1999, “The role of copper in neurodegenerative disease,” Neurobiology of Disease; 6(4): 221-230. [Web Reference]

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