Mercury-containing metallothioneins

Adverse effects of mercury to fishes, in addition to those listed on reproduction and growth, have been documented at water concentrations of 0.88-5.0 xg/L enzyme disruption in brook trout (Salvelinus fontinalis) embryos immersed for 17 days in solutions containing 0.88 ig/L, as methylmercury decreased rate of intestinal transport of glucose, fructose, glycine, and tryptophan in the murrel (Channa punctatus) at 3.0 (xg Hg +/L for 30 days altered blood chemistry in striped bass (Morone saxatilis) at 5.0 xg Hg +/L in 60 days and decreased respiration in striped bass 30 days post-exposure after immersion for 30-120 days in 5.0 xg Hg +/L. In large-mouth bass, elevated liver metallothioneins are indicative of elevated muscle mercury concentrations, suggesting that mercury-induced metallothioneins may be useful biomarkers of mercury exposure. 

Kidney. Since the kidneys receive 20 to 25% of the cardiac output, they will be exposed to a relatively large amount of any systemically administered drug. The kidney also contains a protein, metallothionein, that has a high affinity for metals. This protein is responsible for the renal accumulation of cadmium, lead, and mercury. 

Elemental mercury is oxidized in vivo to inorganic mercury, a bio transformation that is probably catalyzed by catalase. It is selectively accumulated in the kidney and also by lysosomes. Inorganic mercury (Hg2+) will induce the synthesis of metallothionein. Mercury binds to cellular components such as enzymes in various organelles, especially to proteins containing sulfydryl groups. Thus, in the liver, cysteine and GSH will react with mercury to produce soluble products, which can be secreted into the bile or blood. 

Tolerance to heavy metals, specifically mercury and cadmium, has been associated with the induction of kidney metallothionein, a protein rich in sulfhydryl groups which protects by chelation (102). The synthetic antidote dimercaprol, introduced after World War I for arsenic-containing gases, works by a similar mechanism (103). 

For -t-2 cations such as zinc(II) and cadmium(ll) each metallothionein molecule contains up to seven metal atoms. X-ray studies indicate that the metal atoms are in approximately tetrahedral sites bound to the cysteine sulfur atoms. The soft mer-cury(II) ion has a higher affinity for sulfur and will displace cadmium from metallothionein. At first the mercury ions occupy tetrahedral sites but as the number increases, the geometries of the metal sites and protein change until about nine Hg(Il) atoms are bound in a linear (S—Hg—S) fashion.92 Up to twelve + 1 cations such as copper(l) and silver(I) can bind per molecule, indicating a coordination number lower than four, probably three (see Problem 12.34),... 

Heavy metals are well known for inducing the synthesis of a family of metalbinding proteins called metallothioneins (Frazier, 1986). These low-molecular-weight proteins (6000 Da) contain 25-30% cysteine, enabling them to sequester divalent metals such as cadmium, copper, mercury and zinc from the lb and... 

Inorganic mercury salts have a half-life in the body of about 40 days. Mercury binds to a wide range of enzyme systems and has a particular affinity for proteins containing sulphydryl (-SH) groups. As these are widespread, mercury may bind to microsomes and mitochondria, producing a non-specific cytotoxicity and cell death. In the kidney, mercuric mercury induces synthesis of metallothionein, a metal-binding protein, and is foimd localised in lyosomes. 

The first group of methods includes the electrochemical methods based on an oxidation or reduction processes of thiol groups included in the structure of MT. Many authors studied electrochemical behavior of metallothionein containing cadmium and/or zinc ions on the surface of a hanging mercury drop electrode (HMDE) by cyclic voltammetry (CV) [38, 39, 42]. 

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