Copper liver content

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. 

Maximum concentrations of copper in elasmobranchs and teleosts from all collection sites range from 7 to 15 mg/kg DW in eyeballs, intestines, muscle, scales, vertebrae, heart, and gonads and from 16 to 48 mg/kg DW in gills, kidneys, skin, and spleens. They reach 53 mg/kg DW in whole animals, 155 mg/kg DW in stomach contents, 208 mg/kg DW in feces, and 245 mg/kg DW in livers (Table 3.3). 

Liver, gall bladder, kidney Shorebirds Chile November 1981-March 1982 near abandoned copper mine liver vs. stomach contents 11-15 DW 137... 

Initial inhibition of sodium uptake and whole body sodium content that were normal by day 28. Abnormal liver enzyme activity. Liver copper increased from 23 mg/kg FW at start to 113 mg/kg FW at day 28... 

Bakka, A. and M. Webb. 1981. Metabolism of zinc and copper in the neonate changes in the concentrations and contents of thionein-bound Zn and Cu with age in the livers of the newborn of various mammalian species. Biochem. Pharmacol. 30 721-725. 

Cows and calves fed low-zinc diets of 25 mg Zn/kg ration showed a decrease in plasma zinc from 1.02 mg/L at start to 0.66 mg/L at day 90 cows fed 65 mg Zn/kg diet had a significantly elevated (1.5 mg Zn/L) plasma zinc level and increased blood urea and plasma proteins (Ram-achandra and Prasad 1989). Biomarkers used to identify zinc deficiency in bovines include zinc concentrations in plasma, unsaturated zinc-binding capacity, ratio of copper to zinc in plasma, and zinc concentrations in other blood factors indirect biomarkers include enzyme activities, red cell uptake, and metallothionein content in plasma and liver (Binnerts 1989). 

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. 

Copper is an essential trace element absorbed in the gut and transported to the liver bound to albumin. It is found in a variety of enzymes, including superoxide dismutase. In the bloodstream Cu is present mostly in ceruloplasmin. Tissues with a relatively high content of Cu are liver, heart, and brain. The RDA for Cu in normal, healthy adults is 0.9 mg day-1, but newborns usually have liver levels higher than those of adults. The concentration of Cu in mature milk ranges between 0.2 and 0.3 mg l-1 in colostrum it is higher (0.4-0.6 mg l-1), but decreases along the lactation period (see the Chapter 13 by de la Flor St Remy et al.). 

The second step in zinc absorption involves the intracellular interaction of zinc with various compounds which may enhance or impede absorptive processes. In 1969, Starcher noted that radioactive copper, given orally, associated with a low molecular weight protein (25). Subsequently, this mucosal protein was isolated and characterized by Richards and Cousins, who classified it as a metallothionein (26), and who further showed that it was induced in response to zinc administration (5). The appearance of this metallothionein, with properties similar to those described for both rat (27) and human (28) liver metallothionein, appears to be related to changes in both dietary zinc status and plasma zinc levels (5). The synthesis of mucosal metallothionein has been shown to be under transcriptional control (29,30). Menard al. reported that dietary zinc administration resulted in enhancement of metallothionein mRNA transcription and its subsequent translation, to yield nascent metallothionein polypeptides(31). The intestinal metallothionein appearance was correlated to both an increase in mucosal zinc content primarily associated with the protein and with a decrease in serum zinc levels. In addition. Smith e al., using the isolated, vascularly perfused intestinal system, reported an inverse relationship between the synthesis of metallothionein and zinc transfer to the portal system, confirming earlier studies (32). 

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