Thiol-groups mercury

Interaction with thiol groups Mercurials (q. v.) Membrane-bound enzymes... 

It is generally accepted that the basis of the biological activity of mercury compounds is their reaction with the thiol groups, but the biological action is rather more complicated. Frank (1955) showed that mercury compounds can influence the effect of enzymes which do not contain thiol groups. Mercury also reacts with the phosphoryl groups of the cell membranes (Bassow et a/., 1961) and with the amino and carboxyl groups of the enzymes (Lipscomb et al., 1968). Webb (1966) lists more than 40 enzymes inhibited by mercury compounds. 

Mercuric chloride, other mercury-containing antibacterials and silver will inhibit enzymes in the membrane, and for that matter in the cytoplasm, which contain thiol, -SH, groups. A similar achon is shown by 2-bromo-2-nitropropan-l,3-diol (bronopol) and iso-thiazolones. Under appropriate condihons the toxic action on cell thiol groups may be reversed by addition of an extrinsic thiol compound, for example cysteine or thioglycollic aeid (see also Chapters 12 and 23). 

We note in passing that DNA-refilicase has an essential thiol group which is labelled by mercurials. To our knowledge no studies of the effect of platinum on the replicase have been made and this is clearly an omission which should be rectified. In some proteins platinum derivatives would seem to go for the same sites as mercury(II) reagents — a not surprising result as their chemistry is similar. 

Examples of noncompetitive inhibitors are the heavy metals which act as poisons such as lead, mercury and silver ions. Mercury is attracted to -SH(thiol) groups in the active sites of enzymes... 

Der Terrossian, E. Pradel, L.-A. Kassab, R. Desvages, G. Separation of the two non-identical subunits of lombricine kinase from Lumbricus terrestris muscle by chromatography on sepharose-mercurial. Isolation of the tryptic peptide containing its essential thiol group. Eur. J. Biochem., 45, 243-251 (1974)... 

The role of GSH in cellular protection (see below) means that if depleted of GSH, the cell is more vulnerable to toxic compounds. However, GSH is compartmentalized, and this compartmentalization exerts an influence on the relationship between GSH depletion or oxidation and injury. The loss of reduced GSH from the cell leaves other thiol groups, such as those in critical proteins, vulnerable to attack with subsequent oxidation, cross-linking, and formation of mixed disulfides or covalent adducts. The sulfydryl groups of proteins seem to be the most susceptible nucleophilic targets for attack, as shown by studies with paracetamol (see chap. 7), and are often crucial to the function of enzymes. Consequently, modification of thiol groups of enzyme proteins, such as by mercury and other heavy metals, often leads to inhibition of the enzyme function. Such enzymes may have critical endogenous roles such as the regulation of ion concentrations, active transport, or mitochondrial metabolism. There is... 

Thiol groups have a high affinity for mercury ions including organic mercury derivatives, which are widely used in the determination of protein structures by X-ray crystallography (Section F). Titration of SH groups in proteins is often accomplished with... 

Toxic heavy metals, such as cadmium, lead, and mercury, are sulfur seekers that bind strongly with thiol groups, which is one of the ways in which they interact adversely with biomolecules, including some enzymes. Advantage has been taken of this tendency to use thiols in chelation therapy in heavy metal poisoning. Among the thiols tested for this purpose are meso-2,3-dimer-captosuccinic acid, diethyldimercapto succinate, a-mercapto-P-(2-furyl), and a-mercapto-P-(2-thienyl) acrylic acid.3 The structural formulas for the first two are... 

Mercury and its compounds were used for centuries as ingredients in antibacterial drugs, skin creams, and antiseptics. Mercury compounds are quite toxic, however. In the body, mercury combines with the thiol groups of critical enzymes, inactivating them. Mercury poisoning causes brain and kidney damage, often leading to death. 

Thimerosal (Merthiolate) has been used as a topical antiseptic for many years. Its antimicrobial effect is mostly due to the toxicity of the mercury atom that is bound and stabilized by the thiol group of ortho-mercaptobenzoic acid. The carboxylate salt of the acid is used to enhance solubility of this organomercurial compound. 

Mercurials, silver compounds Interaction with thiol groups... 

Mercury interferes with mitochondrial oxidation in the brain through mercaptide formation with thiol groups in pyruvate oxidase. Succinic dehydrogenase of the citric acid cycle is also inhibited. 

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