The inhibition of cytochrome c oxidase by nitric oxide using S-nitrosoglutathione.
The effect of the free radical nitric oxide (NO) on the activity of isolated cytochrome sigma oxidase was investigated by using ferrocytochrome sigma as an electron donor, and the system SNOG/DTT, which produces a steady-state NO concentration similar to that expected to be found in vivo. The initial electron entry into the heme a/Cu a center and the initial rate of the electron transfer between the two hemes were not affected by the presence of NO. Under our conditions, the rate of inhibition of cytochrome c oxidase was found to be dependent both on the SNOG (NO concentration) and on the ferrocytochrome c concentration (electron entry rate). The data confirm that NO binds exclusively at the binuclear center, and that the NO binding in these conditions requires the presence of an intermediate populated only in turnover. Accordingly, we found that the rate of inhibition is directly related to the electron entry rate. In addition, a residual activity seems to be present in cytochrome c oxidase in the presence of nitric oxide, suggesting that NO can act as an electron acceptor to cytochrome c oxidase in the presence of oxygen.
Torres
J
J
Department of Biological and Chemical Sciences, University of Essex, United Kingdom.
Davies
N
N
Darley-Usmar
V M
VM
Wilson
M T
MT
D003574:Cytochrome c Group / Q000737:chemistry / Q000378:metabolism; D004229:Dithiothreitol / Q000737:chemistry / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D007700:Kinetics; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D026422:S-Nitrosoglutathione; D013057:Spectrum Analysis / Q000379:methods
D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D005609:Free Radicals; D009603:Nitroso Compounds; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D003576:Electron Transport Complex IV; D005978:Glutathione; D004229:Dithiothreitol