Plasma metallothionein levels

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). 

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). 

Reports concerning metallothionein in plasma and urine of Cd-exposed persons are limited [47-49]. This is at least in part due to the fact that the accurate measurement of Cd and metallothionein levels in plasma appears to be difficult [50]. The concentration of metallothionein in urine and blood has to be measured using the Onosaka saturation method, radio-immunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). The detection limits in human serum and urine for metallothionein by RIA is 1 pg [50]. For ELISA the detection limits are higher. Normal values range between 0.01-1 ng/ml for serum and between 1-10 ng/ml for urine. Metallothionein concentrations in Cd-exposed workers are reported to vary between 2-11 ng/ml in plasma and 2-155 ng/ml in urine [47]. 

High levels of zinc stimulate the synthesis of metallothionein in the small intestines. The elevated levels of metallothionein then serve as a depot for the binding of high levels of zinc consumed in subsequent meals. The induced protein has been shown to limit the amount of zinc entering the bloodstream with consumption of a high-zinc diet (Menard ef o/., 1981). High doses of copper can induce metallothionein synthesis to the same extent as can zinc. At levels near those found in the diet, zinc is a potent inducer while copper is only a weak inducer. Normally, hepatic metaiiothionein contains mainly zinc, whereas kidney metallothionein contains copper and, when present in the diet, cadmium. The copper entering the liver may be stored in hepatic metallothionein and released into the plasma in ceruloplasmin or secreted in the bile later. 

Auto-antibodies against metallothionein can be determined in plasma by enzyme-linked immunosorbent assay. It was shown in an occupationally Cd-exposed group in China, that persons with elevated levels of antibodies against metallothionein in plasma displayed a greater sensitivity to developing renal tubular dysfunction - odds ratio 4.2 (95% Cl 1.2-14.5) [161]. In a group of Chinese type-2 diabetics with uri-... 

Biochemistry of Zinc and Copper Zinc in the -Cells of the Pancreas Absorption of Zinc and Copper Plasma Zinc and Copper Levels Metallothionein and Ceruloplasmin Zinc Excretion and Zinc Deficiency Copper Excretion and Copper Deficiency Genetic Diseases of Copper Metabolism Molybdenum, Sulfite, and Sulfate Molybdenum Molybdenum Biochemistry Sulfite Sulfate... 

If one had to state an overall role of copper in the body, one might say oxygen metabolism. One major factor shared by both zinc and copper is that both metal ions occur bound to metallothionein. The function of metallothionein is not firmly established. Copper is bound to another protein, ceruloplasmin, which occurs in the cell and plasma. The function of this protein is not clear either. Zinc absorption, as iron absorption, is impaired by high levels of phytic acid. Copper absorption is not inhibited by phytic acid. The major route of excretion of both metal ions is fecal, rather than urinary. 

Absorbed zinc is predominantly transported by plasma albumin, although a2-macroglo-bulin and possibly transferrin are also involved. Hypoalbuminemia influences therefore not only the zinc levels in plasma and serum, but also zinc absorption. There exists an exchange of zinc between its intracellular pools (high molecular-weight zincbinding proteins and metallothionein) and different organ systems as a major part of homeostasis besides absorption and excretion (Silverman and Rivlin 1982, Henkin and Aamodt 1983, Solomons and Cousins... 

Blood. It is likely that Cd is bound for at least 70% to the red blood cells. Therefore, plasma or serum levels are considered to be so low as to be indeterminable. Beside this, due to hemolysis internal contamination may appear. Binding in erythrocytes may be partly to hemoglobin, but also binding to higher as well as lower molecular mass proteins (metallothionein) has been reported [7]. Binding in plasma may be to albumin, to metallothionein, and to SH groups of other proteins. 

CDU Is bound principally to metallothionein, regardless of whether the cadmium originates from metallothionein in plasma or from the cadmium pool accumulated in the renal tubules. Therefore, measurement of metallothionein in urine may provide information similar to CDU, while avoiding the contamination problems that may occur during collection and handling urine for cadmium analysis (Nordberg and Nordberg 1988). However, a commercial method for the determination of metallothionein at the sensitivity levels required under the final cadmium rule is not currently available therefore, analysis of CDU is recommended. 

Prange et al. analyzed the isoforms of metallothioneins in human brain cytosol with capillary electrophoresis (CE) coupled to ICP-SFMS (inductively coupled plasma-sector field mass spectrometry). In the study, three metal-lothionein isoforms were separated by CE, and the enriched isotopes of Cu, Zn, Cd, and were mixed as a specific-unspecific spiking solution finally, the Cu, Zn, Cd, and S in metallothioneins were quantified with IDA. They found that the levels of MT-3 and MT-1 were lower in the brain samples from the patients with Alzheimer s disease in comparison with the controls (see Figure 4.8). The results indicated that quantification of metalloproteins gave additional information on its relationship with Alzheimer s disease. ... 

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