Absorption of copper

Absorption of copper in adult women consuming a formula diet has been reported to average 57.7 + 17.7% (18). Our absorption figures for copper fall into this range. 

As with copper, zinc is an essential element for all plants and animals. It is necessary for the correct function of various enzyme systems. However, excessive intakes of zinc can have long-term effects as they can interfere with absorption of copper and iron in the diet, and may result in anaemia.39 JECFA has recommended a PTDI of 1 mg/kg bodyweight, equivalent to 60 mg/day for a 60 kg adult.38 In food, the major contributors to the diet are meat and its products, from which zinc is readily absorbed. Liver, with concentrations of around 62 mg/kg, contains the highest levels of any meat products, with other tissues having values of a half to a third of this figure. The second greatest source of zinc is cereals. Concentrations of zinc in whole cereal products are similar to those in meat. 

Mir Y, Houde D, Van Lier JE. Two-photon absorption of copper tetrasulfophthalocya-nine induces phototoxicity towards jurkat cells in vitro Photochem Photobiol Sci 2006 5 1024-30. 

Hendricks, G.M., Guo, M.R., Kindstedt, P. 2001. Solubility and relative absorption of copper, iron, and zinc in two milk-based liquid infant formulae. Int. J. Food Sci. Nutr. 52, 419-428. 

Ascorbic acid Is known to Increase the Intestinal absorption of non-heme Iron but to decrease the absorption of copper (29-35). 

The use of COCs in patients with Wilson s disease remains controversial. There are reports suggesting that COCs will increase plasma caeruloplasmin, leading to increased absorption of copper, and this could exacerbate the disease [21]. No data are available to evaluate this risk objectively. Patients should therefore use POCs [2],... 

ANTACIDS COPPER 4- plasma concentration of copper Most antacids will i absorption of copper If antacids are used in the long term, consider copper supplements of 1-2mg/day... 

Intestinal absorption of copper is mediated by coppertransporting P-type ATPase 7A (ATP7A) or Menkes disease protein. Mutations in the ATP7A gene lead to Menkes disease in humans that is characterized by congenital impairment in intestinal transport of copper see Metal-related Diseases of Genetic Origin) ... 

Zinc salts Inhibits intestinal absorption of copper by induction of intestinal cell metallothionein may also induce hepatic metallothionein 150-200 mg of elemental zinc orally in divided doses... 

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. 

Molybdate is known to induce copper deficiency, ft was found that the administration of molybdenum compounds, particularly with added sulfate, impaired copper metabolism in ruminants. Tetrathiomolybdate has been used to treat patients who were intolerant to D-penicillanune, trientine, and zinc. Tetrathiomolybdate seems to act both by blocking the intestinal absorption of copper and keeping it in a metabolically inert chelated form, which is not taken up by the liver. However, it induces only a modest cupriuresis. There are also known toxic effects of tetrathiomolybdate on the skeletal system of growing animals. Thus one should be extremely careful in administering this compound. It should be considered as an experimental drug. 

Treatment of Menkes patients have concentrated on restoring normal copper levels in the body by administering copper. Since the intestinal absorption of copper is very low in Menkes patients, copper must be administered parenteraUy. Copper has been administered in various forms including copper chloride, copper sulfate, copper EDTA, and copper-albumin. But none of these copper compounds is able to produce significant clinical improvement, especially in... 

Details of copper determination are also discussed by Menzies (M6) and Strasheim et al. (Sll). Elwell and Gidley (E2) examined the effect of many elements including silicon and found no interference on the absorption of copper. 

From 30 to 50% of dietary copper is absorbed by humans. As with zinc, the extent of Copper absorption changes with nutrient status. Studies with humans have revealed that a large proportion of dietary copper (56%) is absorbed by the gut with the consumption of diets low in copper (0.8 mg Cu/day). A low proportion (12%) of the dietary copper is absorbed with high-copper diets (8.0 mg Cu/day) (Tumiimd et a ., 1939). Absorption of copper was determined by feeding diets containing a stable isotope of copper, copper-65, and measuring the fecal losses. 

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 copper (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. ... 

Two genetic disorders of copper metabolism, Wilson s disease (see Section 62.2.3.3) and Menkes disease, are known. The latter involves impaired intestinal absorption of copper as well as probably subcellular metabolic defects which result in copper deficiency with respect to metal-loenzyme activity. The characteristic steely hair in Menkes disease results from free SH bonds in hair protein because of failure of lysyl oxidase to produce the disulfide links. Depigmentation of hair and skin, hypothermia, cerebral degeneration, central nervous system retardation, skeletal demineralization and arterial degeneration are all seen. Copper supplements may benefit hypothermia and increase pigmentation but the disease is not generally cured. 

In the diet and at the tissue level, ascorbic acid can interact with mineral nutrients. In the intestine, ascorbic acid enhances the absorption of dietary iron and selenium reduces the absorption of copper, nickel, and manganese but apparently has little effect on zinc or cobalt. Ascorbic acid fails to affect the intestinal absorption of two toxic minerals studied, cadmium and mercury. At the tissue level, iron overload enhances the oxidative catabolism of ascorbic acid. Thus, the level of dietary vitamin C can have important nutritional consequences through a wide range of inhibitory and enhancing interactions with mineral nutrients. 

The mechanism of this eflFect is not known. Hill and Starcher (49) postulated that reduction of copper from its divalent (cupric) state to its monovalent (cuprous) state accounted for the impaired absorption of copper in the presence of ascorbic acid they produced the same effect with another reducing agent, dimercaptopropanol (BAL). This explanation has been accepted by others (56), although the oxidation state of copper for maximum intestinal absorption has not been established. An intramucosal competition of ascorbic acid for sulfhydryl sites on metallo-thioneins was demonstrated (57). If this ligand has any regulatory role in copper uptake, this alternative mechanism of ascorbic acid-copper interaction could explain the mechanism. Experimental confirmation of an ascorbic-acid-induced inhibition of copper absorption in the human intestine has not been presented. 

Menkes disease A sex-linked inherited disorder, causing defective gastrointestinal absorption of copper and resulting in copper deficiency early in infancy. 

Petruzzelli, G., Guidi, G., and Sequi, P. (1975). The absorption of copper by roots in relation to chelating properties of soil organic matter. In Studies about Humus. Trans. Int. Symp. Humus et Planta VI., pp. 18-22. 

R. R. Grinstead, Selective Absorption of Copper, Nickel, Cobalt and Other Transition Metal Ions from Sulfuric Acid Solutions with the Chelating Ion Exchange Resin XFS4195, Hydrometallurgy, 12, pp. 387-400 (1984). 

The combination of manganese and vanadium or of nickel and vanadium administered to pregnant mice caused some alterations in behavioral development of the pups as compared to either element administered alone (Hoshishima et al. 1983). Oral administration of vanadium in rats interfered with copper metabolism, probably by inhibiting the intestinal absorption of copper (Witkowska et al. 

The absorption of copper from the bowel can be influenced by a number of inorganic substances. Anions, which have a tendency to form highly insoluble salts with copper under the conditions prevailing in bowel contents, tend to reduce the absorption of copper. Sulfide is the best known of these. Cupric sulfide is poorly absorbed by rats and pigs (B21, S23). Addition of sulfides to the diet markedly reduces copper absorption in animals (D5) and man (C5). Of the cations, molybdenum is known to influence copper retention in animals. It is suspected that molybdenum influences the membrane transport of copper in such a way that absorption is decreased and excretion increased (D6). For details of this problem the reader is referred to Underwood s monograph (U2) and a recent review by Mills (M25). Problems of this nature have not yet been encountered in man. Oral doses of potassium sulfide and certain ion-exchange resins are used to reduce the absorption of copper in certain pathological conditions in man (C5). 

Although certain factors influencing the absorption of copper from the intestine are recognized, we have no concept of the mechanism of absorption nor do we know the regulatory mechanisms which influence the rate of absorption. The suggestion of Scheinberg and Morell (S16) that ceruloplasmin may be involved in the regulation of copper absorption could not be substantiated. 

Hypocupremia and low serum ceruloplasmin levels were reported in celiac disease (A13, LI), and in tropical (B36) and nontropical sprue (Cl, S40). Oral administration of copper to the patients with tropical sprue resulted in a sustained rise of serum copper in only one of four patients (B36). Stemlieb and Janowitz (S40) have recently shown that in nontropical sprue the absorption of copper from the gut is impaired. 

In order to explain the presence of vastly increased copper stores in the tissues of patients with Wilson s disease, it was suggested that the absorption of copper from the gastrointestinal tract is increased. The finding of markedly positive copper balances in seven patients by two groups of investigators (C4, Z2) was used as an argument in favor of this contention. However, the validity of this argument is questionable, since decreased excretion via the bile can equally well explain the experimental data. Whether the patient with Wilson s disease absorbs copper in excess of the normal amounts is an imanswered question. 

By what mechanism the abnormal amounts of copper are deposited in the body is not known. Scheinberg and Gitlin (S15), finding very low serum ceruloplasmin levels in these patients, suggested that an inability of the patient to synthesize this protein is basically at fault. Absorption of copper... 

In Menkes syndrome intestinal absorption of copper is defective. How can affected infants be treated to avoid the symptoms of the disorder, which include seizures, retarded growth, and brittle hair ... 

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