Excretion of copper

About 50% of copper in food is absorbed, usually under equitibrium conditions, and stored in the tiver and muscles. Excretion is mainly via the bile, and only a few percent of the absorbed amount is found in urine. The excretion of copper from the human body is influenced by molybdenum. A low molybdenum concentration in the diet causes a low excretion of copper, and a high intake results in a considerable increase in copper excretion (68). This copper—molybdenum relationship appears to correlate with copper deficiency symptoms in cattle. It has been suggested that, at the pH of the intestine, copper and molybdate ions react to form biologically unavailable copper molybdate (69). 

The cause of Wilson disease was also revealed in 1993, when it was reported that a variety of mutations in a gene encoding a copper-binding P-type ATPase were responsible. The gene is estimated to encode a protein of 1411 amino acids, which is highly homologous to the product of the gene affected in Menkes disease. In a manner not yet fully explained, a nonfunctional ATPase causes defective excretion of copper into the bile, a reduction of incorporation of copper into... 

Retention of radiocopper injected into humans is high only 10% is excreted within 72 h in urine and feces, and 50% in four weeks (Aaseth and Norseth 1986). Most (72%) of the unabsorbed copper is excreted in the feces primarily by way of the biliary duct, the salivary glands, or the intestinal mucosa a minor portion is excreted by way of sweat and menses (Schroeder et al. 1966 USEPA 1980 ATSDR 1990). In mammals, copper is excreted mainly via the bile in association with glutathione or unidentified high-molecular-weight molecules. However, the transport mechanisms of copper from liver cells into bile are essentially unknown (Aaseth and Norseth 1986). In rats, biliary excretion of copper is increased by increased flow of bile, increased body temperature, or administration of adrenal steroids (Sugawara et al. 1994). 

In mammals, phenobarbital and phenytoin increase serum ceruloplasmin concentrations (Aaseth and Norseth 1986). Chronic copper poisoning in sheep is exacerbated when diets contain heliotrope plants (Heliotropium sp., Echium spp., Senecio sp.). Aggravated effects of the heliotrope plants include reduced survival and a twofold to threefold increase in liver and kidney copper concentrations when compared to control animals fed copper without heliotropes (Howell et al. 1991). Rats given acutely toxic doses of 2,3,7,8-tetrachlorodibenzo-para-dioxin had elevated concentrations of copper in liver and kidney because of impaired biliary excretion of copper (Elsenhans et al. 1991). Morphine increases copper concentrations in the central nervous system of rats, and dithiocarbam-ates inhibit biliary excretion (Aaseth and Norseth 1986). In human patients, urinary excretion of copper is increased after treatment with D-penicillamine, calcium disodium EDTA, or calcium trisodium diethylenetriamine penta acetic acid (Flora 1991). 

Sugawara, N., D. Li, M. Katakura, and C. Sugawara. 1994. Biliary excretion of copper in Fischer rats treated with copper salt and in Long-Evans Cinnamon (LEC) rats with an inherently abnormal copper metabolism. Biol. Trace Elem. Res. 46 125-134. 

Yu, S., C.E. West, and A.C. Beynen. 1994. Increasing intakes of iron reduce status, absorption and biliary excretion of copper in rats. Brit. Jour. Nutr. 71 887-895. 

Increasing dietary Mo resulted in decreasing copper retention due to increasing excretion of copper in feces up to 1.45 g Mo/kg BW absorbed and retained with no obvious adverse... 

Mechanism of Action A heavy metal antagonist that chelates copper, iron, mercury, lead to form complexes, promoting excretion of copper. Combines with cystine-forming complex, thus reducing concentration of cystine to below levels for formation of cystine stones. Exact mechanism for rheumatoid arthritis is unknown. May decrease cell-mediated immune response. May inhibit collagen formation. Therapeutic Effect Promotes excretion of copper, prevents renal calculi, dissolves existing stones, acts as anti-inflammatory drug. 

For patients who are unable to tolerate penicillamine, trientine, another chelating agent, may be used in a daily dose of 1-1.5 g. Trientine appears to have few adverse effects other than mild anemia due to iron deficiency in a few patients. Zinc acetate administered orally increases the fecal excretion of copper and is sometimes used for maintenance therapy. The dose is 50 mg three times a day. Zinc sulfate (200 mg/d orally) has also been used to decrease copper absorption. Zinc blocks copper absorption from the gastrointestinal tract by induction of intestinal cell metallothionein. Its main advantage is its low toxicity compared with that of other anticopper agents, although it may cause gastric irritation when introduced. 

The same investigators subsequently reported increased urinary excretion of copper and iron, as well as zinc, in patients receiving TPN (2). They also detected sugar-amine compounds in the TPN solutions and in the patients urine and plasma. 

Copper is an essential element to most life forms. In humans it is the third most abundant trace element only iron and zinc are present in higher quantity. Utilization of copper usually involves a protein active site which catalyzes a critical oxidation reaction, e.g., cytochrome oxidase, amine oxidases, superoxide dismutase, ferroxidases, dopamine-/ -hydrox-ylase, and tyrosinase. Accordingly, animals exhibit unique homeostatic mechanisms for the absorption, distribution, utilization, and excretion of copper (J). Moreover, at least two potentially lethal inherited diseases of copper metabolism are known Wilson s Disease and Menkes s Kinky Hair Syndrome (I). 

Biliary excretion of copper and iron is important. Major losses of iron can be caused by internal bleeding. Thus women during their menstrual periods will be in negative iron balance unless proper nutrition is observed. Blood loss via the gastrointestinal tract, as in ulcers or some forms of cancer, leads quickly to loss of utilizable or stored iron. ... 

D-Penicillamine Reduction and chelation of copper. Urinary excretion of copper by mobilizing copper from organs 1 - 2 g orally in divided doses... 

Trientine (triethylenetetramine) was used in 1982 to treat Wilson disease as an alternative to D-peiticillamtne. It is also a chelator of copper and increases urinary excretion of copper. There is less experience with the use of trientine compared to D-penicillamine. Its toxicity is relatively unexplored. The initial effect of this treatment is large cupriuresis but its rate diminishes more rapidly than with D-penicillamine. However, it should be pointed out that this treatment is effective especially in situations for which D-penicillamine must be... 

Zinc was known to produce copper deficiency in experimental animals. The first report of zinc treatment for Wilson disease was published in 1979. Zinc causes induction of metallothionein in the intestinal cells, which binds copper with high affinity and holds it with high affinity until the intestinal cells are sloughed off. Thus, zinc inhibits absorption of copper from the intestine and increases the fecal excretion of copper. Zinc also blocks the reabsorption of endogenously secreted copper from sahva and gastric juice. A major advantage of zinc treatment is its low toxicity. 

The main route of excretion of copper from the body is via the feces. Urine contains extremely small amounts of copper (4-30 ig/day in man) (B33). Sweat contains only negligible quantities (M26). There is very little copper in saliva, and it is recirculated. Insignificant amounts are lost by menstruation (L6). 

Evidence is accumulating to suggest that, in addition to the defect in the synthesis of ceruloplasmin, another mechanism whereby copper is discharged from the liver is also disturbed, namely, excretion of copper via the bile. There is only indirect evidence for this, consisting mainly of two observations ... 

Following intravenous administration of Cu% patients with Wilson s disease excrete much less of the Cu in the stools than normal individuals (see Section 4.3). Since a high percentage of fecal Cu is excreted into the gastrointestinal tract via the bile, this also suggests that the biliary excretion of copper is impaired in Wilson s disease. 

Ingestion, absorption, distribution, utilization and excretion of copper complexes 442... 

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