The inhibition of mitochondrial cytochrome oxidase by the gases carbon monoxide, nitric oxide, hydrogen cyanide and hydrogen sulfide: chemical mechanism and physiological significance |
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Authors: | Chris E Cooper Guy C Brown |
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Institution: | (1) Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK;(2) Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK |
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Abstract: | The four gases, nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S) and hydrogen cyanide (HCN) all readily inhibit oxygen consumption by mitochondrial cytochrome oxidase. This inhibition
is responsible for much of their toxicity when they are applied externally to the body. However, recently these gases have
all been implicated, to greater or lesser extents, in normal cellular signalling events. In this review we analyse the chemistry
of this inhibition, comparing and contrasting mechanism and discussing physiological consequences. The inhibition by NO and
CO is dependent on oxygen concentration, but that of HCN and H2S is not. NO and H2S are readily metabolised by oxidative processes within cytochrome oxidase. In these cases the enzyme may act as a physiological
detoxifier of these gases. CO oxidation is much slower and unlikely to be as physiologically important. The evidence for normal
physiological levels of these gases interacting with cytochrome oxidase is equivocal, in part because there is little robust
data about their steady state concentrations. A reasonable case can be made for NO, and perhaps CO and H2S, inhibiting cytochrome oxidase in vivo, but endogenous levels of HCN seem unlikely to be high enough. |
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Keywords: | Cytochrome oxidase Mitochondria Inhibition Nitric oxide Carbon monoxide Hydrogen cyanide Hydrogen sulfide |
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