Copper in tissues

Wilson s disease is a pathological accumulation of copper in tissue which is later released into the bloodstream, leading to anaemia, and final accumulation of copper in liver and brain. It is the result of a mutation in the Wilson s disease gene in chromosome 13 which ordinarily codes for a cation transporting ATPase so that copper can be incorporated into ceruloplasmin prior to excretion. Also known as ferroxi-dase, in acknowledgement of its primary function as an oxidoreductase responsible for electron transfer, this enzyme contains iron and, more importantly, six copper atoms. It accounts for the transport of 90% of copper in the plasma so any impairment in its production or efficacy has a major impact on copper homeostasis. The greatly reduced concentration of ceruloplasmin in the blood of Wilson s disease sufferers correlates with their inability to metabolize copper effectively. It leads to chronic liver disease, for which the only real cure is a liver transplant,... 

The above methods have all been, or could easily be, adapted for the chemical determination of copper in tissues. 

Copper in Tissues and Biological Fluids 3.1. Copper Content... 

Kl. Kaiser, D. G., and Meinke, W. W., Rapid activation analysis of trace copper in tissue using 5.1-minute copper-66. Anal. Biochem. 6, 77-81 (1963). 

Interpretation of Wilson s disease on the basis of disrupted copper metabolism is far from complete. The accumulation of copper in tissues is generally considered responsible for the lesions of the liver (cirrhosis), renal tubules (amino aciduria), and basal ganglia (neurological disorder), but the special affinity of these various tissues for copper remains to be explained, as does the mechanism of copper toxicity in these organs. Penicillamine, a copper-chelating substance, has been administered for treatment of Wilson s disease with some degree of success. In fact, it has even been claimed that asymptomatic victims of Wilson s disease can be treated preventively [56]. 

The interpretation of results from studies with radiocopper in patients with Wilson s disease are all bedevilled with the possibility that the radiocopper has simply been diluted in a greatly expanded body pool of the metal. If this is the case the finding of a low concentration of labelled copper in tissue, urine or faeces is simply a measure of dilution [59, 115]. However, the distribution of radiocopper in both patients and control... 

What is the concentration of copper, in micrograms per gram FFDT, for a 11.23-mg FFDT tissue sample that yields an absorbance of 0.023 ... 

Substituting the sample s absorbance into the preceding equation gives the concentration of copper in solution as 0.351 ppm. The concentration in the tissue sample, therefore, is... 

The special interest is the determination of Fe, as the acceleration of sclerosed process is connected with the accumulation of Fe in this organ. Copper is accumulated in tissues at the genetic caused diseases (Wilson Disease, Hemochromatosis). This is the alteration in elemental ratios (e.g., Cu/Zn), that is the marker of pathological process. 

Metallothioneins are a group of small proteins (about 6.5 kDa), found in the cytosol of cells, particularly of liver, kidney, and intestine. They have a high content of cysteine and can bind copper, zinc, cadmium, and mercury. The SH groups of cysteine are involved in binding the metals. Acute intake (eg, by injection) of copper and of certain other metals increases the amount (induction) of these proteins in tissues, as does administration of certain hormones or cytokines. These proteins may function to store the above metals in a nontoxic form and are involved in their overall metaboHsm in the body. Sequestration of copper also diminishes the amount of this metal available to generate free radicals. 

Stevens, B. J. "Biological Applications of the Carbon Rod Atomizer In Atomic Absorption Spectroscopy. 2. Determination of Copper In Small Samples of Tissue". Clin. Chem. (1972), 18, 1379-1384. 

Adults require 1-2 mg of copper per day, and eliminate excess copper in bile and feces. Most plasma copper is present in ceruloplasmin. In Wilson s disease, the diminished availability of ceruloplasmin interferes with the function of enzymes that rely on ceruloplasmin as a copper donor (e.g. cytochrome oxidase, tyrosinase and superoxide dismutase). In addition, loss of copper-binding capacity in the serum leads to copper deposition in liver, brain and other organs, resulting in tissue damage. The mechanisms of toxicity are not fully understood, but may involve the formation of hydroxyl radicals via the Fenton reaction, which, in turn initiates a cascade of cellular cytotoxic events, including mitochondrial dysfunction, lipid peroxidation, disruption of calcium ion homeostasis, and cell death. 

In muscle of Weddell seals (Leptonychotes weddelli), copper is positively correlated with iron (Szefer et al. 1994). In general, concentrations of copper in all tissues of all marine vertebrates examined are positively correlated with concentrations of iron (Eisler 1984). 

Copper concentrations in field collections of plants and animals are usually elevated in areas treated with copper-containing herbicides, near smelters, and from heavily urbanized and industrialized areas (Stokes 1979 Eisler 1984 Winger et al. 1984 Read and Martin 1993 Swiergosz et al. 1993 Fishelson et al. 1994 Storm et al. 1994). The amount and distribution of copper in animal tissues varies with tissue, organism age, sex, and amount of copper in the diet (Cuill et al. 1970 NAS 1977 USEPA 1980 Fishelson etal. 1994). Additional and more detailed information on copper concentrations in field collections of plants and animals is found in Jenkins (1980) and Eisler (1979, 1981). 

Marine mammals usually contain less than 44 mg Cu/kg DW in all tissues except livers. Copper in livers seldom exceeds 116 mg/kg DW except in polar bears (146 mg/kg DW), and manatees, Trichechus manatus, (1200 mg/kg DW) from a copper-contaminated site (Table 3.3). Maximum copper concentrations in terrestrial mammals from all collection sites are usually less than 29 mg/kg DW in all tissues except kidneys (108 mg/kg DW) and livers (1078 mg/kg DW Table 3.3). 

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