Metallothioneins metal complexes

LASER-FLASH KINETIC ANALYSIS METAL ION CATALYSIS METALLOTHIONEINS Metal-nucleotide complex,... 

MT have been subdivided into three classes, namely I, II, and III (Fowler et al. 1987), while Binz and Kagi (1999) allocated these compounds to several families. Subsequently, Richards and Beattie (1995), Richards et al. (1996, 1997) and Szpunar (2000) showed capillary zone electrophoresis to be a rapid and reliable method for analysis of this protein. By using a diverse combination of techniques, the metal complexes of metallothionein in rat liver and kidney were first characterized, with two major MT-isoforms (MT-1 and MT-2) being detected in liver, and one MT isoform in kidney (Polec et al. 2002). The order of afHn-ity of metal ions to MTs is Cd > Zn, Cu, Ag, Hg > Bi > Pb, though this may change depending on the tissue involved. MTs are considered to be low molecular-weight pro-... 

SzpuNAR J, Ribas B and Lobinski R (2002) Investigation of metal complexes with metallothionein in rat tissues by hyphenated techniques. J Inorg Biochem 88 197-206. 

An additional mechanism for transport of metal complexes is by endo-cytosis/exocytosis (for review see Ballatori 1991). Fluid-phase, adsorptive, and receptor-mediated endocytosis make a major contribution to the transport of metals that are bound to high molecular weight ligands, and in particular to ligands such as ferritin, transferrin, and other proteins that are selectively cleared by receptor-mediated endocytosis. Because these proteins also have some affinity for toxic metals, they may play an important role in their transport across cell membranes (Ballatori 1991). The mechanism by which metallothionein and its associated metals are removed from the circulation is not known, but the kidney appears to be the principal site of removal (Tanaka et al. 1975). When rats are injected intravenously with ° Cd-labeled metallothionein, the radioactivity is rapidly and nearly completely accumulated in the kidney (Tanaka et al. 1975). 

Transporting soft metal centres is important in protection against toxic metals such as and Hg. Complexation requires soft ligands, which are provided by Nature in the form of cysteine residues (Table 29.2) in thioneins. The metal complexes that thioneins form are called metallothioneins. Thioneins also bind Cu and but their active... 

Mounicou, S., Polec, K., Chassaigne, H., Potin-Gautier, M., and Lobinski, R. (2000) Characterization of metal complexes with metallothioneins by capillary zone electrophoresis (CZE) with ICP-MS and electrospray (ES)-MS detection. J. Anal. At. Spectrom., 15, 635 2. 

Robbins, A.H. and Stout, C.D. (1992) Metallothioneins Synthesis, Structure and Properhes of Metallothioneins, Phytochelatins, and Metal-Thiolate Complexes (eds M.l. ShDman, C.F. Shawlll and KT. Suzuki), VCH Publishers, Weinheim, pp. 31—54. 

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... 

It turns out that the six-membered Cu3( -8)3 rings are paradigmatic units. This type of ring system has been incorporated into current models of metallothioneins [low-molecular-weight proteins which are believed to play a key role in metal metabolism (cf. references in 136)]. The structural chemistry of the Ag complexes seems to be different. Monocyclic Ag(8 ) rings can be linked via bridging ligands as in [(86)Ag(88)Ag(86)] (133) or condensed as in [Ag2(86)2] " (28) (126). 

Thioneins are apoproteins that are exceptionally sulfur-rich (composed of greater 30 mol% cysteine). These proteins are found in high abundance in liver and kidney cytoplasm where they form metallothioneins (the holo-protein forms) upon complexation with metal ions. Thi-onein synthesis is induced by the presence of metals, especially zinc, copper, mercury, and cadmium. 

Also, different metallothioneins, a group of peptides and proteins, which play an important role in metabolism of metals in living organisms, have been studied [101, 102]. In the range of more anodic potentials, cycKc voltammograms recorded in the absence of metal ions were similar to those obtained for disulfide-containing proteins. The presence of metal ions in the solution shifted the voltammetric peaks, depending on the stability of the formed complex. 

Metal ions can serve as effector molecules as well as control the DNA-binding activity of regulatory proteins. An example is the regulation of the metallothionein gene in eucaryotes (Fig. 1.23). The metallothioneins are small, cysteine rich proteins which can specifically bind metal ions like Cu or Zn The complexation of metal ions functions to sequester the ions in a form that is not damaging to the cell. 

The gene for metallothionein is induced by metal ions. The goal of the regulation is to provide enough metallothionein for the complexation of metal ions and thus to maintain the concentration of free metal ions at a tolerable level for the cell. 

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