Copper excretion

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). 

Wilson s disease is another autosomal recessive disease leading to cirrhosis. Protein abnormalities result in excessive copper deposition in body tissues. The faulty protein is responsible for facilitating copper excretion in the bile, so copper accumulates in hepatic tissue. High copper levels within hepatocytes are toxic, and fibrosis and cirrhosis may develop in untreated patients. Those with Wilson s disease usually present with symptoms of liver or neurologic disease while still in their teens. 

Increase in blood and urine Mo levels, increases in serum ceruloplasmin, increased xanthine oxidase activity (11) Increased uric acid, decreased copper excretion, high incidence of gout-like disease (11)... 

A word of comment on the high Cu64 content of the bile seems justifiable, since the exact chemical form of copper excreted in the bile has not been determined. The possibility that ceruloplasmin or some copper-containing metabolite of ceruloplasmin is normally excreted in the bile has not been carefully examined. The abnormal elevation of the serum ceruloplasmin level in acute biliary obstruction (7), and the abnormally low serum ceruloplasmin seen in some cases of advanced liver disease, particularly Wilson s disease (2, 3), are in keeping with the liver being the site of ceruloplasmin synthesis and excretion. 

Wilson s disease is a copper storage disorder that is apparently due to an inherited lesion in the copper excretion mechanism. One in 200-400 persons is a carrier of the disease. Diagnosis may be made by measuring serum ceruloplasmin levels. Whereas normal serum ceruloplasmin is 200-400 mg/L, in Wilson s disease patients it is well below 200 mg/L. Liver copper in these patients (determined by biopsy) is more than 250 /xg/g, whereas normal individuals show a value of only 20-45 /xg/g. Liver function deterioration is the most prominent symptom of Wilson s disease. Treatment includes chelation therapy with penicillamine. 

The disturbance of copper excretion, primarily due to a defect in the billiary excretion, is consistent with the biochemical findings in patients with Wilson disease. Urinary copper excretion is increased owing to total body overload of copper. Renal dysfunction includes albuminuria and renal rickets. Incorporation of copper in ceruloplasmin is impaired. Thus, there is a greater proportion of copper bound to albumin and amino acid complexes in the serum. But the overall copper concentration in serum is low. Ceruloplasmin is a multicopper oxidase see Copper Proteins Oxidases) that... 

Cupruria In pronounced liver cell decay, there is not only a rise in the copper value in serum, but more particularly in the amount of copper excretion in the urine. Cupruria of < 50 pg/day rules out the presence of Wilson s disease (differential diagnosis e.g. kidney disease). The penicillamine test has proved successful after administration of 600 mg penicillamine, copper excretion increases to > 300 pg/6 hr (> 600 pg/24 hr). However, it should be noted that this test may show similar positive results in cholestatic liver diseases. 

Confirmation The diagnosis is verified by laboratory parameters (determination of the serum values of copper and ceruloplasmin as well as of copper excretion in the urine, if necessary also by means of the penicillamine test) and by demonstration of the copper content of the liver, with simultaneous differentiation of existing liver damage. 

Davis, W., Chowrimootoo, G.F.E., Seymour, C.A. Defective biliary copper excretion in Wilson s disease the role of caeruloplasmin. Eur. J. Clin. Invest. 1996 26 893-901... 

In patients with Wilson s disease, penicillamine is rapidly attached to copper and, although higher doses are used, taste disturbances develop in a lower frequency, about 4% (SED-8, 536). It has been suggested that dysgeusia is related to deficiency of copper or zinc, but a strong connection between taste impairment and urinary copper excretion has not been demonstrated (118). Serum copper concentrations remained within normal limits and copper supplements were not effective in prevention (119). 

Iron compounds reduce the systemic availability of penicillamine to about 35% and copper excretion to about 28%, probably as a result of catalysis of the oxidation of penicillamine to its disulfide (2,398,400). Even the iron present in certain multivitamin formulations can be sufficient to cause interference, and when a patient who has regularly taken iron stops taking it, increased absorption of penicillamine and adverse effects can ensue (401,402). 

Biochemistry of Zinc and Copper Zinc in the -Cells of the Pancreas Absorption of Zinc and Copper Plasma Zinc and Copper Levels Metallothionein and Ceruloplasmin Zinc Excretion and Zinc Deficiency Copper Excretion and Copper Deficiency Genetic Diseases of Copper Metabolism Molybdenum, Sulfite, and Sulfate Molybdenum Molybdenum Biochemistry Sulfite Sulfate... 

Copper Excretion and Serum Ceruloplasmin in Liver Disease, Scand. J. Gastroenterol. (1977) 12 81-SS. 

MK 681 Syprine ) is an organic base, a CHELATING AGENT used orally in the treatment of Wilson s disease (to aid copper excretion). 

The chronic form of Wilson s disease is treated by oral chelating agents, such as penicillamine and trientine, that remove excess copper from tissue and increase urine copper excretion. Oral administration of zinc salts or ammonium molybdate, which block copper intestinal absorption, has also been successful. ... 

Treatment of active, symptomatic Wilson s disease is aimed at increasing urine copper excretion to eliminate excess copper from tissue. The primary therapy for Wilson s disease involves chelating agents such as o-penicillamine and trientine, which is now more widely used because of its lower rate of side effects. In patients with minimal symptoms or in asymptomatic family members, zinc is used to competitively inhibit copper absorption from the intestinal tract. Lifelong therapy with one of these types of treatment is required and is usually successful in limiting further damage. 

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