Antagonism of nitric oxide toward the inhibition of cytochrome c oxidase by carbon monoxide and cyanide.

Chem Res Toxicol

Department of Environmental and Occupational Health, Graduate School of Public Health, The University of Pittsburgh, 130 DeSoto Street, Pittsburgh, Pennsylvania 15261, USA.

Published: November 2008

The principle mitochondrial target where the respiratory inhibitors CO, CN(-), and NO act in the execution of their acute toxic effects is complex IV of the electron-transport chain, cytochrome c oxidase. However, there is a paucity of studies in the literature regarding the concerted effects of such poisons. Accordingly, the combined inhibitory effects of CO + CN(-), NO + CN(-), and NO + CO on the activity of cytochrome c oxidase preparations are reported. Only in the case of CO + CN(-) do the effects of the two inhibitors seem to be additive as expected. NO appears to be antagonistic toward the effects of the other two inhibitors; that is, the effects of both CO an CN(-) on enzyme activity are ameliorated by NO when present. To further clarify these observations, the ligand substitutions of heme-bound CN(-) by NO in cytochrome c oxidase and hemoglobin have also been briefly investigated. These results suggest that displacement of CN(-) from the ferric hemoproteins by NO is rate-limited by heme reduction-and in the case of the enzyme, the presence of nonligand-binding electron-transfer centers facilitates the reaction. The findings are discussed in relation to the idea that NO does not behave as a classic reversible (by dissociation) inhibitor.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773210PMC
http://dx.doi.org/10.1021/tx800140yDOI Listing

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