Heavy metals metallothioneins binding

Metallothioneins (MTs) are small proteins with an especial affinity for the binding of various heavy metals active in a wide range of reactions [95-97]. Besides their role in... 

Teigen SW, Andersen RA, Daae HL, Skaare JU. 1999. Heavy metal content in liver and kidneys of grey seals Halichoerus grypus) in various life stages correlated with metallothionein levels some metal-binding characteristics of this protein. Environ Toxicol Chem 18 2364-2369. 

Elevated metallothionein levels are not necessarily indicative of heavy-metal insult. Starcher et al. (1980) show that liver metallothionein levels in mice are elevated following acute stress or starvation, and that this effect is blocked by actinomycin D, a protein synthesis inhibitor. It is further emphasized that not all zinc-binding proteins are metallothioneins (Webb etal. 1985 ... 

When animals are fed experimental diets lacking copper or zinc, their copper or zinc status rapidly declines, suggesting that there is not a storage pool of these metals. Thus, while the small, cysteine-rich protein metallothionein (see below) can avidly bind zinc and copper, this may reflect its role in detoxification rather than as a specific storage form. This is reflected by the fact that metallothionein genes are typically expressed at a basal level, but their transcription is strongly induced by heavy metal load. 

Grill, E., Winnacker, E.-L. Zenk, M.H. (1987). Phytochelatins, a class of heavy metal binding peptides from plants are functionally analogous to metallothioneins. Proceedings of the National Academy of Sciences (USA) 84, 439-43. 

Metallothionein expression is mainly regulated at the transcriptional level and is induced by various heavy metals, such as zinc. There are seven short sequence motifs located in a region within 200 base pairs upstream of the transcription start site. These cis-acting DNA elements are responsible for heavy metal induction and are thus termed metal responsive elements (MREs) (Stuart et al., 1984). Several regulatory proteins have been cloned which interact with these MREs. One of these, MRE-binding transcription factor-1 (MTF-1), is essential for the transcriptional activation of metallothionein genes by heavy metals like zinc and cadmium (Radtke et al., 1993 Palmiter, 1994 Heuchel et al., 1994 Koiszumi et al., 1999). 

Metallothionein Small molecular weight protein family, rich in cysteine, that binds strongly to divalent heavy metals. The synthesis is under the control of essential metals like zinc and copper. Other metals such as cadmium, mercury and silver can induce its concentration in cells. Volume 1(14). 

A kind of hyposensitivity is that induced by repeated exposures to a toxic substance leading to tolerance and reduced toxicides from later exposures. Tolerance can be due to a less toxic substance reaching a receptor or to tissue building up a resistance to the effects of the toxic substance. An example of the former occurs with repeated doses of toxic heavy metal cadmium. Animals respond by generating larger quantities of polypeptide metallothionein, which is rich in -SH groups that bind with Cd2+ ion, making it less available to receptors. 

In response to the presence of detrimental Cd +, Hg +, Pb +, and other heavy metal ions, the human hver and kidneys synthesize more metallothionein, an unusual small protein in which approximately one-third of the 61 amino acid residues are cysteine see Metallothioneins). The frequency and juxtaposition of sulfhydryl groups provide strong binding sites for several heavy metal ions. Though not as profusely as metallothionein, many proteins contain sulfhydryl groups that may become metalated by toxic heavy metal ions such as Cd +, Hg +, and Pb +, and it is widely believed that this complex formation explains the toxicity of these metal ions. The exact proteins where the most consequential damage occurs remain uncertain. 

Peptides and proteins could be efficient metal binding ligands, because they have the functional groups for metal binding in their amino acid residues, and they can be produced at low cost by recombinant technologies. While many peptides and proteins are known to work as metal transport proteins in biological systems, metallothioneins (cysteine rich proteins with molecular weight of ca. 7 kDa) have attracted researchers attention for decades because they bind heavy metals in vivo [2]. The metallothioneins are considered to be involved in detoxication and metabolism of heavy metals. 

The metabolism of zinc is influenced by hormones, stress situations, lipopolysaccharides, toxins, oxygen radicals, lipid peroxidations, etc. This may lead to fluctuations in the zinc concentration, mainly due to the induction of metallothioneine (MT), which is a transport and intracellular depot protein. One third of this protein consists of cysteine, which binds zinc, copper, cadmium, cobalt and mercury. This protects the body from toxic heavy metal... 

The metal-binding proteins metallothionein and ceruloplasmin are recurring themes in the study of zinc and copper Metallothionein is a small protein with a protein binds zinc and copper ions, as well as nonnutritive heavy metals. The protein consists of about 60 amino acids, and has a molecular wreight of about 7000. One third of these amino acids (20 of them) are cysteine. The 20 sulfhydryl groups of these cysteine residues can bind a total of 7 bivalent metal ions, i.e., 7 zinc atoms or 7 copper atoms (l agi and Schaffer, 1988). 

Like pesticides, heavy metals are traditionally tested by enzyme inhibition or modulation of catalytic activity. Several metalloproteins behave as chelators for specific metals with no known catalytic reactions. Such heavy metal binding sites exist in metallothioneins and in various protein elements of bacterial heavy metal mechanisms and have been exploited for specific detection through affinity events. Nevertheless and as previously mentioned, bacterial resistance mechanisms can also be linked to catalytic pathways. For instance, c5rtochromes c3 and hydrogenases from sulfate and sulfur reducing bacteria [284,285] are well suited for bioremediation purposes because they can reduce various metals such as U(V) and Cr(VI) [286,287]. Cytochrome c3 has been reported to catalyse Cr(VI) and U(VI) reduction in Desulfovibrio vulgaris [288,289], suggesting... 

In plants, two kinds of metal-binding peptides or proteins are synthesized. Plant metallothioneins are inducible cysteine-rich entities very like those found in animals. Differential expression (induction) of metallothionein genes can be due to both variation of external heavy metal concentrations and the influence of various environmental factors. The principle role of plant metallothioneins seems to be in homeostasis rather than in metal detoxification. Plants are also known to have so-called phytochelatins, which are non-protein thiols specifically induced upon exposure to heavy metals. A close positive relationship between the concentrations of cadmium and phytochelatins in the plant shoot material has been observed and linked to the degree of growth inhibition (Keltjens and Van Beu-sichem, 1998). These observations make the use of phytochelatins promising for the assessment of heavy metal effect on plants. 

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. 

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