Absorption copper

Copper is associated with two important life-threatening diseases in man, the pathologies of both being due to defective intracellular copper transport. Menke s disease is characterized by progressive cerebral degeneration, essentially due to insufficient copper absorption, and Wilson s disease is due to excessive copper accumulation in liver, accompanied by liver disease and haemolytic crises. 

In mammals, cadmium inhibits copper absorption across the intestinal mucosa (Aaseth and Norseth 1986). Intercorrelations of copper with cadmium and zinc in livers of polar bears (Ursus maritimus) are probably mediated by metallothioneins, which may contain all three metals (Braune etal. 1991). In rats, copper protects against nephrotoxicity induced by cadmium, provided that copper is administered 24 h prior to cadmium insult. Specifically, rats given 12.5 mg Cu/kg BW by way of subcutaneous injection 24 h before receiving 0.4 mg Cd/kg BW — when compared to a group receiving Cd alone — did not have excessive calcium in urine and renal cortex or excessive protein in urine. Thus, 2.8 mg Cu/kg BW protects against 0.25 mg Cd/kg BW (Liu et al. 1992). 

In mammals, copper absorption across the intestinal mucosa is inhibited by concomitant high oral intake of zinc (Aaseth and Norseth 1986). In livers from Weddell seals, copper is positively correlated with zinc (Szefer et al. 1994). The addition of zinc to swine diets protects against copper toxicosis caused by eating diets containing 250 mg Cu/kg ration (USEPA 1980). 

The relation between copper toxicosis, copper absorption rates, and copper retention (Stokes 1979 ATSDR 1990)... 

Handy, R. D., Musonda, M. M., Phillips, C. and Falla, S. J. (2000). Mechanisms of gastro-intestinal copper absorption in the African Walking Catfish copper dose-effects and a novel anion-dependent pathway in the intestine, J. Exp. Biol.,... 

Therapy may be monitored with a 24-hour urinary copper analysis periodically (ie, every 6 to 12 months). Urine must be collected in copper-free glassware. Because a low copper diet should keep copper absorption down to less than 1 mg/day, the patient probably will be in the desired state of negative copper balance if 0.5 to 1 mg of copper is present in a 24-hour collection of urine. 

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. 

Copper absorption is depressed by ascorbic acid, dietary phytuies. cadmium, mercury, silver, and zinc. It appears that metals impede copper absorption through competition lor meml-hinding sites. Dietary copper, molybdenum, amt sulfur arc closely interrelated in optimum copper und molybdenum nutrition of ruminants. Increase pasture molybdenum content and low-pasture copper result in a condition known as "peat scours. ... 

For the most part, adequate copper is received in diet and widespread human deficiencies do not occur, but deficiencies may arise because of antagonists. The metals Cd, Hg, Ag and Zn interfere with copper metabolism, probably by competing for copper-binding sites in proteins. Ascorbic acid depresses intestinal absorption of copper56 (in contrast to iron). Some proteins in the diet adversely affect utilization of copper. The sulfide ion is a well known inhibitor of copper absorption, since it forms copper(II) sulfide which is insoluble.56... 

COPPER CONCENTRATION (ppm) Fig. 3. Calibration curves for different copper absorption lines. 

In a recent study we compared zinc absorption from different protein sources. Five young women were fed diets containing 70% animal protein for 21 days and 70% vegetable protein for another 21 days. The results of the study are shown in Table VI. There was no significant difference in zinc absorption between the two diets. Copper absorption was determined in this study also and did differ significantly between the two diets. 

We have used stable Isotopes in several other zinc absorption studies. Sample analysis Is In progress from a study In which Zn was used to determine the effects of phtate and cellulose on zinc absorption In man. Studies were also conducted to determine zinc absorption from vegetarian diets, the effect of vitamin B-6 status on zinc absorption, and the effect of level of dietary zinc on zinc and copper absorption. 

Subsequent studies have given some insight into the cellular mechanisms of the copper zinc interaction. Evans al. (29) found the 1000 1 Zn/Cu ration inhibited 64Cu uptake only in zinc-deficient rats, and that its effect was not on uptake from the lumen, but rather on transfer to the body. Parenteral injection of copper prior to luminal dosing with 65Zn also reduced net copper absorption (32) (Fig 3) but again, this was due to reduced transfer of copper across and out of the mucosal cell. Also, in the study of Van Campen (31) of the effect of excess copper on zinc absorption, indications of a predominant Influence within the mucosal cell were developed. 

Three human metabolic studies have examined the effect of dietary zinc Intake on apparent copper absorption. Greger et al. (37) studied 11 adolescent girls, ranging in age from 12.5 to... 

Competitive mineral-mineral interactions involving chemically similar elements are widespread in nature. Interactions between zinc and iron, and zinc and tin reduce zinc absorption in humans, and pose potential nutritional consequences. Dietary zinc levels may also be of Importance in human copper absorption. Natural foods, alone or in combination, tend to have a balance among minerals, but in the formulation of proprietary vitamin-mineral supplements or Infant foods, there is the potential for creating nutrltionally-signlflcant Imbalances. Little is known about the role of other food components in conditioning these interactions. This question should be a priority for future research. 

Copper absorption appears to occur through both a rapid, low-capacity system, and a slower, high-capacity system, which may be similar to the two processes seen with calcium absorption. Inactivating mutations in the gene encoding an intracellular copper ATPase have been shown to be responsible for the failure of intestinal copper absorption in Menkes disease. 

Interactions Overabundance of one trace element can interfere with the metabolic use of another element available at normal levels. For example, addition of large amounts of zinc to a diet interferes with (antagonizes) intestinal copper absorption, resulting in copper deficiency from a diet with adequate copper content. Copper deficiency can provoke iron deficiency and anaemia. Molybdenum deficiency in animals can be induced by co-administration of large amounts of the similar element tungsten. Iron deficiency can also increase retention of cadmium and lead, and selenium has been proposed to protect against cadmium and mercury toxicity. 

Treatment While damage cannot be cured, disease progression can be slowed down by lifelong chelation therapy. These chelating agents (including d-penicillamine or trientine hydrochloride) can help remove copper from tissue, and zinc supplements may help slow copper absorption, but patients also need to follow a diet low in copper. In extreme conditions where patients do not respond to treatment, liver transplantation may be an option. 

The best known of these is the interference of copper absorption caused by zinc due to the induction of intestinal metallothionem this binds to copper and prevents its entry into the bloodstream. The intestinal cells eventually slough, carrying the copper with them. The prolonged intake of zinc necessitates copper supplements except in patients with Wilson s disease. 

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