Sharpe 1998 J Biol Chem

Sharpe MA, Cooper CE (1998) Interaction of peroxynitrite with mitochondrial cytochrome oxidase: Catalytic production of nitric oxide and irreversible inhibition of enzyme activity. J. Biol. Chem. 273: 30961-30972.

Sharpe MA, Cooper CE (1998) J. Biol. Chem.

Abstract: Purified mitochondrial cytochrome c oxidase catalyzes the conversion of peroxynitrite to nitric oxide (NO). This reaction is cyanide-sensitive, indicating that the binuclear heme a₃ /CuB center is the catalytic site. NO production causes a reversible inhibition of turnover, characterized by formation of the cytochrome a₃ nitrosyl complex. In addition, peroxynitrite causes irreversible inhibition of cytochrome oxidase, characterized by a decreased Vmax and a raised Km for oxygen. Under these conditions, the redox state of cytochrome a is elevated, indicating inhibition of electron transfer and/or oxygen reduction reactions subsequent to this center. The lipid bilayer is no barrier to these peroxynitrite effects, as NO production and irreversible enzyme inhibition were also observed in cytochrome oxidase proteoliposomes. Addition of 50 µM peroxynitrite to 10 µM fully oxidized enzyme induced spectral changes characteristic of the formation of ferryl cytochrome a₃ , partial reduction of cytochrome a, and irreversible damage to the Cu_A site. Higher concentrations of peroxynitrite (250 µM) cause heme degradation. In the fully reduced enzyme, peroxynitrite causes a red shift in the optical spectrum of both cytochromes a and a₃ , resulting in a symmetrical peak in the visible region. Therefore, peroxynitrite can both modify and degrade the metal centers of cytochrome oxidase

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Preparation: Oxidase; Biochemical Oxidation"Oxidase; Biochemical Oxidation" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property.  Enzyme: Complex IV; Cytochrome c Oxidase"Complex IV; Cytochrome c Oxidase" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property.  Regulation: Respiration; OXPHOS; ETS Capacity"Respiration; OXPHOS; ETS Capacity" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property. 

HRR: Oxygraph-2k