Metallothioneins General

Metallothionein proteins are the most abundant intracellular, metal-binding proteins (Andrews, 2000). Four metallothionein isoforms have been identified in the mouse (MT-I-MT-IV) and are clustered within 50 kilobases of each other. In humans, there is one MTII gene and a cluster of MT I genes on chromosome 16 (Searl et al., 1984 West et al., 1990 Heuchel et al., 1995). The mammalian metallothioneins generally consist of 61 amino acids and 20 of these are cysteines (Heuchel et al., 1995). These cysteines are important for the binding of such bivalent metal ions, such as zinc, copper and cadmium. 

Buchet JP, Eauwerys R, Roels El, Bernard A, Bruaux P, Claeys F, DucofFre G, De Plaen P, Staessen J, Amery A, Eijnen P, Thijs L, Rondia D, Sator F, Saint-Remy A, Nick L. Renal effects of cadmium body burden of the general population. Eancet 1990 336 699-702. Nordberg GF, Goyer RA, Nordberg M. Comparative toxicity of cadmium metallothionein and cadmium chloride on mouse kidney. Arch Pathol 1975 99 192-197. 

It has been known for some time that Wilson s Disease in inherited as an autosomal recessive trait and that its prevalence in the general population amounts to one in 200,000 ( 82,89,90). The cause for the ceruloplasmin deficiency seems to be attributable to impairment of the lysosomal ability to excrete copper into bile, which is the major excretory route for copper (80,81). Bile pigments are known to be good copper chelators (91). In addition, a copper metallothionein with high binding capacity for copper has been identified in livers of subjects with Wilson s Disease (92) and in human fetal liver (93). 

In response to heavy metal exposure, certain plants and yeasts produce PCs, analogous to the sulfur-rich protein metallothionein made by vertebrates. PCs are sulfur-rich peptides of the general chemical makeup (y-Glu-Cys) -Gly where = 2 -11 (Fig. 7.7). PCs are... 

Several classes of molecules are involved in metal homeostasis. Metallothioneins (MTs) are a family of cysteine-rich metal-binding proteins that in mammals appear to function in Zn homeostasis and protect against heavy metal toxicity and oxidative stress60. Glutathione (GSH) is a sulfhydryl-rich tripeptide that is generally involved in the protection of cells against toxicants and in the metabolism of xenobiotics71. MTs and GSH are found in fish, and their expression and functions have been conveniently studied with piscine cell lines. 

Metallothionein is a metal-binding protein whose level generally increases in response to exposure to metals (Hennig 1986), although the demonstration that its level is also increased by exposure to hydrocarbon fuel oil even in the absence of metals illustrates the care that must continuously be exercised in interpreting data on enzyme levels (Steadman et al. 1991). 

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