Mercury react with proteins

Silver-silver chloride electrodes have the advantage that they can be used at temperatures greater than 60 C. whereas calnmel electrodes cannot. On the other hand, mercury(ll) ions react with fewer sample components lhan do silver ions (which can react with proteins. for example) such reactions can lead to plugging of the junction between the electrode and the analyte solution. 

From his studies with ethacrynic acid, Cafruny concludes that ethacrynic acid does react with protein-bound sulfhydryl of renal cells. He further states that the data indicate that ethacrynic acid occupies the same "receptors and may share the same mechanism of action as the mercurials" and that ethacrynic acid "probably blocks reabsorption of soditjm in the same way as mercurials and in most respects is the "non-mercurial mercurial" diuretic it was designed to be". 

Neuberg and Popowsky, as also Abderhalden and Kempe, have introduced a few alterations in the procedure, such as evaporation in vacuo, and Levene and Rouiller suggested in 1906 that the tryptophane, on account of its proneness to decompose on evaporation of its solution with consequent loss, be estimated colorimetrically the mercury sulphate precipitate is decomposed, and the solution, freed from hydrogen sulphide, is titrated with bromine water in presence of amyl alcohol. Both cystine and tyrosine react with bromine water the latter can, however, be removed, but for the former a correction has to be made. Up to the present no values concerning the amount of tryptophane in various proteins have appeared, and it will be of interest to see if the values so obtained are very much higher than those obtained by crystallisation of the tryptophane. 

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. 

Confirmation of this possibility comes from the work of Steinberg and Sperling. From the completely reduced protein they have produced a derivative containing 1 mercury atom bridging each of the 4 pairs of sulfur atoms 188). The resulting molecule had two abnormal tyrosine residues and reacted with antiserum to RNase. In a more limited modification 1 mercury atom was introduced specifically at the 65-72 SS group 184). This derivative was fully active and nearly identical to RNase-A. 

A trial was made to take a look at the valence of iron in adrenodoxin (29) using 3 moles of p-chloromercuribenzoate (PCMB) per gram atom of iron (less than saturated level of PCMB), all of the iron could be extracted by 5% trichloroacetic acid solution as ferric iron, which produces a ferrous-o-phenanthroline complex only by the addition of ascorbate as reductant. In the absence of the mercurial, some 50% or more of the iron atoms in the protein can be removed in the ferrous state. This result indicates that the acid extraction causes intramolecular reduction of the protein-bound iron. As shown in Fig. 10, 5.7 M urea as a protein denaturant can slowly bleach the visible absorption under aerobic conditions. About 10% of the residual absorption remains at 414 mp after the reaction is completed. In the presence of both urea and o-phenanthroline, all of the iron present in adrenodoxin reacts with o-phenanthroline to produce the ferrous complex under aerobic conditions. Similar experiments under anaerobic conditions reveal that the... 

Chemical modification of soybean agglutinin by acetylation of its amino groups resulted in little loss of agglutinating activity, whereas the protein was quite sensitive to modification of its tyrosyl residues.547 Failure of the protein to react with 2-iodoacetamide or p-(chloro-mercuri)benzoate in 6 M urea confirmed that it was devoid of sulfhydryl groups. A metalloprotein containing151 Ca2+ and Mn2+, the soybean lectin is inactivated by Al3+, Fe3+, and Pb2+, whereas Mn2+, Ba2+, Mg2+, Ag+, Li+, and K+ are without effect.532... 

Thus, the toxicity of DMM is mediated by its dealkylation. Cleavage of the carbon-mercury bond generates MMM metabolites, which can form covalent bonds with cellular ligands with amphiphilic properties. The mercury center reacts with sulfur and sulfur-containing thiol groups of enzymes and thereby inhibits them. The metal center of DMM acts as a soft acid, and binds tightly to polarizable donor atoms in soft bases. Within cells, mercury may interact with a variety of proteins, particularly microsomal and mitochondrial enzymes. This can severely impair cell function. 

Mercury has a great affinity for sulfydryl moieties and, hence, binds and inactivates a variety of enzymes. Methylmercury also initiates lipid peroxidation, which can produce alterations in cell membranes. Mercury damages the microtubules in the brain by reacting with the protein tubilin. 

Mercury is a reactive element and its toxicity is probably due to interaction with proteins. Mercury has a particular affinity for sulphydryl groups in proteins and consequently is an inhibitor of various enzymes such as membrane ATPase, which are sulphydryl dependent. It can also react with amino, phosphoryl and carboxyl groups. Brain pyruvate metabolism is known to be inhibited by mercury, as are lactate dehydrogenase and fatty acid synthetase. The accumulation of mercury in lysosomes increases the activity of lysomal acid phosphatase which may be a cause of toxicity as lysosomal damage releases various hydrolytic enzymes into the cell, which can then cause cellular damage. Mercury accumulates in the kidney and is believed to cause uncoupling of oxidative phsophorylation in the mitochondria of the kidney cells. Thus, a number of mitochondrial enzymes are inhibited by Hg2+. These effects on the mitochondria will lead to a reduction of respiratory control in the renal cells and their functions such as solute reabsorption, will be compromised. 

Pollard KM, Lee DK, Casiano CA, Bluthner M, Johnston MM, Tan EM. The autoimmunity-inducing xenobiotic mercury interacts with the autoantigen fibrillarin and modifies its molecular and antigenic properties. J Immunol 1997 158 3521-3528. Kubicka-Muranyi M, Kremer J, Rottmann N, Lubben B, Albers R, Bloksma N, Luhrmann R, Gleichmann E. Murine systemic autoimmune disease induced by mercuric chloride T helper cells reacting to self proteins. Int Arch Allergy Immunol 1996 109 11-20. 

Of the many cysteines in LDH, it is unusual for the essential thiol to be the first to react with a covalent modifying reagent 132,133). In the dogfish enzyme the nonessential cysteine-266 reacts first with mercurials. In Pig H4 the essential thiol reacts with maleimide 198) in the native state. In other species and isozymes the protein has to be first dissociated 132) or denatured 199) before the essential thiol can be covalently labeled. 

Some metal ions, including iron, copper and zinc, are essential in low concentrations for cellular metabolism in bacteria, though at higher concentrations these ions may be toxic. However, other metals such as cadmium, mercury and lead do not play any physiological role and are in fact toxic towards cells. For example, mercury and lead react with sulfhydryl groups of proteins and therefore inhibit their functions. Cad-... 

However, one of the first matrices used for insolubilization of the aflBnant was cellulose that had been partially etherified with 3-hydroxy-phenoxy or 4-diazobenzyl groups (which react with diazotized protein or protein, respectively). Amino compounds may also be attached to the acid chlorides of carboxy polysaccharides.0-(3-Allyloxy-2-hydroxy-propyl)-cellulose and -Sephadex can be mercuriated and, in this form, used for isolation of thiolated antibodies and fractionation of mononucleotides according to their aflBnity for an organomercurial. Another mercurial, prepared by treatment of 0-(2-aminoethyl)Sephadex with IV-acetylhomocysteine thiolactone to give a thiol (49) which, on treatment with 2,5-bis[(acetoxymercuri) methyl]-1,4-dioxane, gives 50, can also be used in aflSnity chromatography of thiolated proteins. 

The thiol group of Cys is the most reactive side residue. The thiolate anion is a potent nucleophile and the thiol is a week acid with pKj = 8.37. Cys serves as the active site residues of many oxidoreductases. Cys residues form complexes of varying stability with a variety of metal ions. It reacts with organic mercurials stoichiometiically. Thiol residues of Cys cross link to form disulfide bonds (cystine) in proteins. Thiols and disulfides undergo rapid exchange and redox reactions. 

The most potent SH-reagents are the mercurials, which react with SH-groups according to the equation Protein-SH + Hg-X Protein-SHg-X-t-H (seeFig.l). 

Naganuma et al., 1980). Selenide has been found to react with methyl-mercury in vitro to form bis(methylmercuric)selenide (reaction 10), but either protein sulfhydryl groups or reduced glutathione was needed when other chemical forms of selenium were used (Iwata et al., 1981). The detection of selenide, although at very low levels, in the tissues of mice treated with selenium and methylmercury (Naganuma et al., 1980) is evidence that this reaction occurs in animals. Hence, there are several possible mechanisms of interaction of selenium with cadmium, mercury, and silver, and many physiological aspects of this interaction still to be elucidated. 

Nowadays mercuiy and its compounds are fully recognised highly toxic substances to humans as well as wildlife, with elemental and organic mercuiy (methyl mercury) considered as the most important concern from the toxicological point of view [26]. These mercuiy compounds have the capacity to penetrate through cell membranes and react with essential proteins, amino acids and nucleic acids within the cells and bound to haemoglobin [27]. Also,... 

In blood, dissolved mercury vapor enters the RBCs and oxidizes to the divalent ionic form (Hg " ). The catalase-H202 complex (compound I) is responsible for this oxidation (see below). Oxidized mercury readily reacts with SH groups of protein or glutathione. 

---