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

Biochimica Et Biophysica Acta
Chris E CooperPeter Nicholls

Abstract

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 ...Continue Reading

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Citations

Dec 25, 2009·Inorganic Chemistry·Jun WangKenneth D Karlin
Dec 23, 2008·Journal of the American Chemical Society·Jun WangKenneth D Karlin
Sep 11, 2009·Antioxidants & Redox Signaling·Giorgio Lenaz, Maria Luisa Genova
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Feb 11, 2010·Biochimica Et Biophysica Acta·Enara AguirreSusana Cadenas
Jun 19, 2009·The Biochemical Journal·Maria G MasonChris E Cooper
Jul 16, 2009·Nitric Oxide : Biology and Chemistry·Catherine N Hall, John Garthwaite
Jul 28, 2020·PLoS Computational Biology·William Davis HaseldenPatrick J Drew
May 1, 2018·Frontiers in Physiology·Alfonsina GattusoSandra Imbrogno
Mar 14, 2009·The Journal of Experimental Biology·Mikkel MisfeldtHans Gesser

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