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A dynamic model of nitric oxide inhibition of mitochondrial cytochrome c oxidase

Cooper, Chris E and Mason, Maria G and Nicholls, Peter (2008) 'A dynamic model of nitric oxide inhibition of mitochondrial cytochrome c oxidase.' Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1777 (7-8). pp. 867-876. ISSN 0005-2728

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Nitric oxide can inhibit mitochondrial cytochrome oxidase in both oxygen competitive and uncompetitive modes. A previous model described these interactions assuming equilibrium binding to the reduced and oxidised enzyme respectively (Mason, et al. Proc. Natl. Acad. Sci. U S A 103 (2006) 708-713). Here we demonstrate that the equilibrium assumption is inappropriate as it requires unfeasibly high association constants for NO to the oxidised enzyme. Instead we develop a model which explicitly includes NO binding and its enzyme-bound conversion to nitrite. Removal of the nitrite complex requires electron transfer to the binuclear centre from haem a. This revised model fits the inhibition constants at any value of substrate concentration (ferrocytochrome c or oxygen). It predicts that the inhibited steady state should be a mixture of the reduced haem nitrosyl complex and the oxidized-nitrite complex. Unlike the previous model, binding to the oxidase is always proportional to the degree of inhibition of oxygen consumption. The model is consistent with data and models from a recent paper suggesting that the primary effect of NO binding to the oxidised enzyme is to convert NO to nitrite, rather than to inhibit enzyme activity (Antunes et al. Antioxid. Redox Signal. 9 (2007) 1569-1579). © 2008 Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: nitrite; enzyme kinetics; nitric oxide; mitochondria; inhibition; cytochrome oxidase
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 16 Sep 2011 09:01
Last Modified: 15 Jan 2022 00:21

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