Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Sharpe 1998 J Biol Chem

From Bioblast
Publications in the MiPMap
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 273:30961-72.

» PMID: 9812992 Open Access

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 CuA 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

O2k-Network Lab: UK Colchester Cooper CE

Labels: MiParea: Respiration 

Stress:Oxidative stress;RONS 

Preparation: Oxidase;biochemical oxidation  Enzyme: Complex IV;cytochrome c oxidase  Regulation: ADP, Inhibitor, Substrate 

HRR: Oxygraph-2k