Mercury, enzyme inhibition inactivation

Recently, a renewable potentiometric urease inhibition biosensor based on self-assembled gold nanoparticles has been developed by Yunhui et al. for the determination of mercury ions [43]. The advantages of self-assembled immobilization are low detection limit (0.05 iM), fast response, and relatively easy regeneration of the biosensors. The assembled gold nanoparticles and inactivated enzyme layers denatured by Hg2+ can be rinsed out via a saline solution with acid and alkali successively. 

Many of the enzymes in our body are also -SH-containing enzymes, and these will be inactivated if we ingest such compounds. As a result of mercury poisoning, many body functions will be inhibited. 

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... 

Glyceraldehyde-3-phosphate dehydrogenase, an enzyme in the glycolytic pathway (Chapter 8), is inactivated by alkylation with iodoacetate. Enzymes that use sulfhydryl groups to form covalent bonds with metal cofactors are often irreversibly inhibited by heavy metals (e.g., mercury and lead). The anemia in lead poisoning is caused in part because of lead binding to a sulfhydryl group of fer-rochelatase. Ferrochelatase catalyzes the insertion of Fe2+ into heme. 

Many pesticides are esters or amides that can be activated or inactivated by hydrolysis. The enzymes that catalyze the hydrolysis of pesticides that are esters or amides are esterases and amidases. These enzymes have the amino acid serine or cysteine in the active site. The catalytic process involves a transient acylation of the OH or SH group in serin or cystein. The organo-phosphorus and carbamate insecticides acylate OH groups irreversibly and thus inhibit a number of hydrolases, although many phosphorylated or carbamoylated esterases are deacylated very quickly, and so serve as hydrolytic enzymes for these compounds. An enzyme called arylesterase splits paraoxon into 4-nitrophenol and diethyl-phosphate. This enzyme has cysteine in the active site and is inhibited by mercury(ll) salts. Arylesterase is present in human plasma and is important to reduce the toxicity of paraoxon that nevertheless is very toxic. A paraoxon-splitting enzyme is also abundant in earthworms and probably contributes to paraoxon s low earthworm toxicity. Malathion has low mammalian toxicity because a carboxyl esterase that can use malathion as a substrate is abundant in the mammalian liver. It is not present in insects, and this is the reason for the favorable selectivity index of this pesticide. 

Noncompetitive inhibition occurs when the inhibition depends only on the concentration of the inhibitor. This is usually caused by adsorption of the inhibitor at a site other than the active site but one which is necessary for activation. In other words, an inactive derivative of the enzyme is formed. Examples are the reaction of the heavy metals mercury, silver, and lead with sulfhydryl groups (—SH) on the enzyme. The sulfhydryl group is tied up by the heavy metal (ESH + Ag" " —> ESAg + H" ), and this reaction is irreversible. This is why heavy metals are poisons they inactivate enzymes in the body. 

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