Metal ion inhibition

Silver and mercury salts have a long history of use as antibacterial agents.241-243 The use of mercurochrome ((40), Figure 18) as a topical disinfectant is now discouraged. Silver sulfadiazene (38) finds use for treatment of severe burns the polymeric material slowly releases the antibacterial Ag+ ion. Silver nitrate is still used in many countries to prevent ophthalmic disease in newborn children.244 The mechanism of action of Ag and Hg is through slow release of the active metal ion—inhibition of thiol function in bacterial cell walls gives a rationale for the specificity of bacteriocidal action. 

Divalent metal ions inhibit the hydrolysis of N-(2-pyridyl)phthalamic acid (60) and N-(2-phenanthrolyl)phthalaxnic acid (61). In the case of (61) the substrate hydrolyzes by a pathway involving intramolecular general acid catalysis, and this pathway is inhibited by metal ions. Deprotonated amide complexes may also be involved leading to catalytically inactive complexes. 

Ferritin has also been compared with iron-dextran by the EXAFS technique.1108 The apoferritin controls the deposition of the core. Reconstitution of ferritin under a range of conditions always gives the same structure, which is not the case in the absence.of apoferritin. There are metal-binding sites on the protein shell. There is evidence for the binding of iron to apoferritin, probably by carboxyl groups, but there is little detailed information on these sites.1098 On the other hand, other metal ions inhibit the formation of ferritin and may do this by binding at or close to the iron sites. Of most significance appear to be results on Tb3+, Zn2+ and V02+,... 

Zabinski, R.F., and Toney, M.D. 2001. Metal ion inhibition of nonenzymatic pyridoxal phosphate catalyzed decarboxylation and transamination. J.Am. Chem. Soc. 123 193-198. 

Enolase catalyzes the trans dehydration of 2-phosphoglycerate to yield phosphoenolpyruvate and water only a small free energy change ( 1 kcal/mol) is associated with the reaction. The process is entropically driven and is readily reversible. This dimeric protein requires a divalent cation for activity and is rather promiscuous in that any one of about nine different cations can activate the enzyme (86). Depending upon the cation studied, the apoenzyme has either one or two metal binding sites per subunit. Metal ions such as Mg + and Mn + have one site per monomer, whereas Co " and Zn + will bind at two sites. In the presence of substrate there are two sites per subunit for all of the metal ions and, depending upon the pH, a third site is also induced. As the pH decreases, the third site is lost but not sites I and II. This third site is an inhibitory site, as the loss of this site parallels the loss of metal ion inhibition (87). The nature of this inhibition is not clear but may be due to the binding of the substrate at the phos-... 

Transition metal ions inhibit alcohol oxidation by reacting with hydroxyperoxy radicals (see Sect. 2.6), viz. 

Van Etten, R.L. Waymack, P.P. Rehkop, D.M. Transition metal ion inhibition of enzyme-catalyzed phosphate ester displacement reactions. J. Amer. Chem. Soc.. 1964, 96. 6782-6785. 

The lack of mutagenicity by metal compounds in bacterial assays may be due to a number of factors (Rossman et al. 1984, 1987). Some metal ions may be excluded from bacterial cells. In that case, no toxicity is seen, even at very high concentrations (Rossman et al. 1984). Essential bacterial enzymes may be more sensitive than their mammalian counterparts to metal ion inhibition, resulting in toxicity which masks the mutagenicity. In some... 

Thermo-oxidation of PET is catalysed by the metal ions (Zn, Mn etc.) used as catalysts in transesterification of dimethyl terephthalate. Compounds which form complexes with these metal ions inhibit their catalytic action in general and improve the stability of PET towards oxidation. These compounds are mainly esters of phosphoric acid, e.g. triphenyl phosphate (see Table 1). 

Vanadate is a strong inhibitor of BAP with a K, of 2—3 pM (13). Phenol enhances vanadate inhibition in the hydrolysis of PNPP, presumably by forming a phenyl vanadate ester [K- = 0.2 pM) which has a greater affinity for the enzyme than the vanadate alone. Note that phenol by itself is a weak competitive inhibitor with a /Cj of 180 mM. For other metal ions, inhibition decreases in the order of tungstate (WO ", Kj = 6 pM) > arsenate (AsO ", = 3—20 pM) > molybdate... 

Enzyme inhibition sensors are of interest in the environmental context, the most used being those involving acetylcholinesterase inhibited by pesticides e.g. these can involve rather complex architectures, and characterisation of such systems by EIS is becoming more widespread. Complex sensor architectures have been used for endocrine disrupters, with similar characterisation by electrochemical impedance. Recently, EIS was used for the first time to characterise the response of glucose biosensors in the presence of heavy metal ion inhibition. ... 

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