Thiol, mercury binding

Gore and Greenwood (296) have reported that the NADP-GDH of Neurospora is inhibited by p-mercuribenzoate and that this inhibition is prevented by inclusion of coenzyme in the reaction mixture. In their experiments, prior treatment with the mercurial precluded binding of reduced coenzyme. However, Blumenthal and Smith (65) have shown that all thiol groups of the native enzyme are reactive with iodoacetate and that this treatment is without effect on catalytic activity, thus excluding any possible direct role for thiol groups in the activity of this enzyme. 

Silver sulfadiazene is a characterized silver complex used as an antibacterial in the treatment of burns. The polymeric aggregation of the material renders it almost insoluble in water but allows for slow release of the active silver ion. Mercury salts, probably acting by non-specific thiol binding, have been known to be bacteriostatic for many years and were of undoubted chemotherapeutic utility in earlier centuries. 

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... 

Shumilla JA, Wetterhahn KE, and Barchowsky A. 1998. Inhibition of NF-kB binding to DNA by chromium, cadmium, mercury, zinc, and arsenite in vitro Evidence of a thiol mechanism. Arch Biochem Biophys 349(2) 356-362. 

The nephrotoxic potential of mercury is related to its accumulation in the proximal tubule region and the intracellular binding to several functional groups, especially thiols, which results in inactivation of different enzymes and inhibition of protein synthesis... 

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. 

---