Metallothionein development

Separation and detection methods Very refined chromatographic and electrophoretic separation techniques have been developed for metallothioneins. The detection is commonly based on the retention time and UV detection. Other researchers measured the element with e.g. ICP-MS to quantify the compotmd. Combination with electrospray MS-MS leads to the unequivocal identification of the species. 

Mammalian metallothioneins typically bind seven metal ions in cluster structures, with bridging sulfur groups, as seen in the x-ray structure of the Cd5Zn2MT complex (86). It is therefore difficult to develop a simple formation-constant description for the binding of metal ions to MT (87), considering that protonation-deprotonation equilibria of the free protein itself should also be taken into account. However, the usefulness of Table VIII as a guide to the affinity of metal ions for mercapto donor ligands is seen in that the ability of metal ions to... 

Richards, M.R 1989a. Recent developments in trace element metabolism and function role of metallothionein in copper and zinc metabolism. Jour. Nutr. 119 1062-1070. 

Palmiter, R.D., Brinster, R.L., Hammer, R.E., Trumbauer, M.E., Rosenfeld, M.G., Birnberg, N.C., Evans, R.M. (1982) Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes. Nature 300,... 

Metallothioneins from Neurospora crassa contain only 25 amino acid residues, but the primary structure is quite similar to the N-terminal part of the mammalian proteins.1454 These data indicate that the gene that codes for the Neurospora crassa metallothionein is evolutionary related to the gene of the vertebrate metallothioneins. Equine metallothionein exists in two major variants (metallothionein 1A and metallothionein 2A), which show remarkable similarities. Some allelic polymorphic variants also occur in man, horse and rabbit. Recent developments have been comprehensively reviewed.14678... 

M. P. Waalkes, P. L. Goering, Metallothionein and other cadmium-binding proteins recent developments, Chem. Res. Toxicol., 3 (1990), 281-288. 

Figure 7 The (a) and a (b) cadmium-thiolate domain structures in mammalian metallothionein. Yellow spheres represent Cys-sulfurs and Green spheres represent Cd(ll) atoms. Based on models developed in our laboratory, for example, Ref. 41...

Cadmium, like zinc, binds to a protein, metallothionein, in the body The presence of cadmium increases the production of this protein by many times (the body increases detoxication, when threatened, which may be a reason for the development of tolerance). Although the binding removes the cadmium and effectively detoxifies it, the cadmium-protein complex is deposited in the kidneys and cadmium is eventually released, whereupon it seriously damages the organ. 

Some causal relations among various urinary indices were identified using path analysis method. Cadmium-induced renal dysfunction develops in the following order Cd exposure —> increased p2-microglobulin and/or metallothionein —> increased excretion of amino-nitrogen and/or total protein —> increased excretion of glucose [76]. 

In Chinese Cd-exposed workers it was demonstrated that those with a high ability to induce metallothionein suffered less tubular damage than those with a low ability to induce metallothionein in peripheral blood lymphocytes [159]. Similar observations were reported from a population group in China environmentally exposed to cadmium [160]. These observations give support for an important role of metallothionein induction in humans and that such induction in peripheral blood lymphocytes can be used as a biomarker of individual sensitivity to development of renal damage. 

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-... 

A striking feature of the cellular effects of bismuth compounds in animals (and one shared only by lead) is the production of intranuclear inclusion bodies of up to 5 ixm in diameter (87), for example, in the tubular epithelial cells of the kidney. Electron probe microanalysis shows that these contain both Bi and S, and so could be a complex with a Cys-rich protein such as metallothionein. Bismuth is known to be a potent inducer of renal metallothionein synthesis, and pretreatment of animals with bismuth salts can prevent some of the toxic side effects induced by cisplatin (88). The role of metallothionein in the pharmacology of bismuth remains to be established, but the strong involvement of zinc, also an inducer of metallothionein synthesis, in the metabolism of skin cells, for example, may be related. Like several other elements of Group V, the development of the biological chemistiy of Bi is hampered by the lack of good physical properties, in particular of a well-behaved NMR isotope. 

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