Nitric oxide, cytochrome c oxidase and myoglobin: Competition and reaction pathways

It is relevant to cell physiology that nitric oxide (NO) reacts with both cytochrome oxidase (CcOX) and oxygenated myoglobin (MbO2). In this respect, it has been proposed [Pearce, L.L., et al. (2002) J. Biol. Chem. 277, 13556–13562] that (i) CcOX in turnover out-competes MbO2 for NO, and (ii) NO bound to reduced CcOX is “metabolized” in the active site to nitrite by reacting with O2. In contrast, rapid kinetics experiments reported in this study show that (i) upon mixing NO with MbO2 and CcOX in turnover, MbO2 out-competes the oxidase for NO and (ii) after mixing nitrosylated CcOX with O2 in the presence of MbO2, NO (and not nitrite) dissociates from the enzyme causing myoglobin oxidation.