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A list of all pages that have property "Has abstract" with value "Nitric oxide (NO) inhibits mitochondrial respiration by decreasing the apparent affinity of cytochrome c oxidase (CIV) for oxygen. Using iNOS-transfected HEK 293 cells to achieve regulated intracellular NO production, we determined NO and O<sub>2</sub> concentrations and mitochondrial O<sub>2</sub> consumption by high-resolution respirometry over a range of O<sub>2</sub> concentrations down to nanomolar. Inhibition of respiration by NO was reversible, and complete NO removal recovered cell respiration above its routine reference values. Respiration was observed even at high NO concentrations, and the dependence of IC<sub>50</sub> on [O<sub>2</sub>] exhibits a characteristic but puzzling parabolic shape; both these features imply that CIV is protected from complete inactivation by NO and are likely to be physiologically relevant. We present a kinetic model of CIV inhibition by NO that efficiently predicts experimentally determined respiration at physiological O<sub>2</sub> and NO concentrations and under hypoxia, and accurately predicts the respiratory responses under hyperoxia. The model invokes competitive and uncompetitive inhibition by binding of NO to the reduced and oxidized forms of CIV, respectively, and suggests that dissociation of NO from reduced CIV may involve its O<sub>2</sub> dependent oxidation. It also explains the non-linear dependence of IC<sub>50</sub> on O<sub>2</sub> concentration, and the hyperbolic increase of ''c''<sub>50</sub> as a function of NO concentration.". Since there have been only a few results, also nearby values are displayed.

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    • Aguirre 2010 Biochim Biophys Acta  + (Nitric oxide (NO) inhibits mitochondrial rNitric oxide (NO) inhibits mitochondrial respiration by decreasing the apparent affinity of cytochrome c oxidase (CIV) for oxygen. Using iNOS-transfected HEK 293 cells to achieve regulated intracellular NO production, we determined NO and O<sub>2</sub> concentrations and mitochondrial O<sub>2</sub> consumption by high-resolution respirometry over a range of O<sub>2</sub> concentrations down to nanomolar. Inhibition of respiration by NO was reversible, and complete NO removal recovered cell respiration above its routine reference values. Respiration was observed even at high NO concentrations, and the dependence of IC<sub>50</sub> on [O<sub>2</sub>] exhibits a characteristic but puzzling parabolic shape; both these features imply that CIV is protected from complete inactivation by NO and are likely to be physiologically relevant. We present a kinetic model of CIV inhibition by NO that efficiently predicts experimentally determined respiration at physiological O<sub>2</sub> and NO concentrations and under hypoxia, and accurately predicts the respiratory responses under hyperoxia. The model invokes competitive and uncompetitive inhibition by binding of NO to the reduced and oxidized forms of CIV, respectively, and suggests that dissociation of NO from reduced CIV may involve its O<sub>2</sub> dependent oxidation. It also explains the non-linear dependence of IC<sub>50</sub> on O<sub>2</sub> concentration, and the hyperbolic increase of ''c''<sub>50</sub> as a function of NO concentration.sub>50</sub> on O<sub>2</sub> concentration, and the hyperbolic increase of ''c''<sub>50</sub> as a function of NO concentration.)