Paradoxical effects of methylmercury on the kinetics of cytochrome c oxidase.
A stoichiometric amount of methylmercuric chloride substantially inhibits cytochrome c oxidase function under steady-state turnover conditions, where the enzyme is using its substrates, cytochrome c and oxygen, rapidly and continuously. Under these conditions, a reduction in activity of approximately 40% is observed. This is in accord with the results of Mann and Auer [Mann, A.J., & Auer, H.E. (1980) J. Biol. Chem. 255, 454-458], who used mercuric chloride and ethylmercuric chloride. Paradoxically, we found that addition of methylmercuric chloride can increase the activity of cytochrome c oxidase during its initial substrate utilization. This rate enhancement, measured under conditions where the enzyme cycles only a few times, is maximal for the resting state of the enzyme. "Pulsed" cytochrome c oxidase (i.e., enzyme that has been recently reduced and reoxidized) is considerably activated with respect to the resting enzyme, showing faster turnover rates (Antonini, 1977; Brunori et al., 1979). No significant rate enhancement upon treatment with methylmercuric chloride is seen in initial substrate utilization if the enzyme is pulsed immediately before the assay. The apparently contradictory effects of methylmercuric chloride on the resting and pulsed states of the oxidase under low turnover conditions may be reconciled by a model in which mercurial binding greatly stabilizes the enzyme in a state resembling that of the pulsed enzyme. A decrease in conformational flexibility may be the basis of the mercurial-induced diminution in activity of the enzyme during steady-state turnover conditions.
D000818:Animals; D002417:Cattle; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D008767:Methylmercury Compounds / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000201:enzymology
D008767:Methylmercury Compounds; D003576:Electron Transport Complex IV; C004925:methylmercuric chloride