Gastrointestinal tract copper

Relatively high levels of copper in pig diets can improve nutritional performance due to the antimicrobial effects in the gastrointestinal tract. However, if land is fertilized with dung from pigs and subsequently grazed by sheep, the sheep may suffer copper toxicity because of their increased susceptibility to copper compared with pigs. Similarly, pig diets would be unacceptable for sheep because of the high levels of copper therein. 

We will discuss in more detail in Chapter 8 how intracellular copper levels are maintained at extremely low levels by a series of copper chaperone proteins, which sequester newly assimilated copper within the cytoplasm of cells and deliver it in a targeted manner to be incorporated into specific copper-containing proteins. While copper uptake across the gastrointestinal tract is poorly understood—most probably utilising the divalent cation transporter... 

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 trace elements iron, copper, zinc, and manganese, however, are excreted via the feces. Not only do the insoluble and unabsorbed dietary metals pass through the gastrointestinal tract, but also continual sloughing off of intestinal cells removes significant amounts of metal from the organism. 

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. ... 

The genetic syndrome referred to as Menkes kinky hair has been studied by Williams et al. (73). No changes were observed following oral copper supplementation in plasma copper concentration or ceruloplasmin concentration in these patients. However, when copper was given intravenously, a rise in ceruloplasmin was seen. The results indicate that in Menkes syndrome, there is a defect in copper-binding protein which leads to excessive losses of copper from the gastrointestinal tract. 

Copper and Ceruloplasmin in the Adults. The human body contains approximately 100-150 mg Cu, most of which is located in the liver. An intake of approximately 5 mg/day is suflBcient to maintain copper balance. Less than half of this copper is absorbed but most of it is excreted through the bile (120). Absorption from the gastrointestinal tract depends on several factors, the most important of which is probably the acidity of the intestinal content. A small portion is excreted in the urine. 

Iron entering the bloodstream from the gastrointestinal tract is thought to be present as Fe , and must be oxidized to Fe before binding to transferrin, which then delivers iron to many different types of cell. The non-enzymic route for oxidation of Fe in serum appears to be too slow for the formation of iron(III) transferrin. As noted in Section 62.1.8.5.1, the copper protein ceruloplasmin has ferroxidase activity, being responsible for the oxidation of Fe" to Fe . It is well known that deficiency of copper influences iron metabolism in animals, in accord with this role for ceruloplasmin. 

Although copper is an essential element, it is much more toxic to cells than such nonessential elements as nickel and cadmium. Acute poisoning from ingestion of excessive amounts of copper salts, most frequently copper sulfate, results in nonspecific toxic-symptoms, a metallic taste, nausea, and vomiting (with vomitus possibly a blue-green color). The gastrointestinal tract can be damaged by ulceration. 

Menkes disease is an X-linked inherited disorder in which dietary copper is absorbed from the gastrointestinal tract but cannot be transported to the vascular space because of the genetic absence of an intracellular ATPase. Hence, copper... 

Copper uptake across the gastrointestinal tract is poorly understood — most probably utihsing the divalent cation transporter DMTl. At the cellular level, Cu is imported across the plasma membrane of mammalian cells as Cu, by members of the CTR family. The CTR family of proteins have been found in yeast and plants, as we saw, but also in humans and other mammals. They contain several methionine-rich motifs at their N-terminus, and conserved cysteine and histidine residues at their C-terminus. Unusually, CTR proteins can mediate the uptake of platinum anticancer drugs into mammalian cells (see Chapter 22). 

The molecular defect in Menkens syndrome, like that in Wilson s disease, resides in a P-type ATPase. The gene for the enzyme is located on the X chromosome. Wilson s disease is characterized by defective biliary excretion in Menkes syndrome, the defect is a failure to transport copper to the fetus during development as well as failure to absorb copper from the gastrointestinal tract after birth. 

Circulated on the basis of Ihe arithmetic mean copper content of the Tarious parts of tiiie gastrointestinal tract. 

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