Control of cytochrome c oxidase activity by nitric oxide.
Over the past decade it was discovered that, over-and-above multiple regulatory functions, nitric oxide (NO) is responsible for the modulation of cell respiration by inhibiting cytochrome c oxidase (CcOX). As assessed at different integration levels (from the purified enzyme in detergent solution to intact cells), CcOX can react with NO following two alternative reaction pathways, both leading to an effective, fully reversible inhibition of respiration. A crucial finding is that the rate of electron flux through the respiratory chain controls the mechanism of inhibition by NO, leading to either a "nitrosyl" or a "nitrite" derivative. The two mechanisms can be discriminated on the basis of the differential photosensitivity of the inhibited state. Of relevance to cell pathophysiology, the pathway involving the nitrite derivative leads to oxidative degradation of NO, thereby protecting the cell from NO toxicity. The aim of this work is to review the information available on these two mechanisms of inhibition of respiration.
Brunori
Maurizio
M
Department of Biochemical Sciences and CNR Institute of Molecular Biology and Pathology, University of Rome La Sapienza, Piazzale Aldo Moro 5, I-00185 Rome, Italy. maurizio.brunori@uniroma1.it
Giuffrè
Alessandro
A
Forte
Elena
E
Mastronicola
Daniela
D
Barone
Maria Cecilia
MC
Sarti
Paolo
P
D001665:Binding Sites; D003300:Copper / Q000737:chemistry; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006418:Heme / Q000737:chemistry; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction
D009569:Nitric Oxide; D006418:Heme; D003300:Copper; D003576:Electron Transport Complex IV