Peroxynitrite-mediated oxidation of ferrous carbonylated myoglobin is limited by carbon monoxide dissociation

Peroxynitrite-mediated oxidation of ferrous nitrosylated myoglobin (Mb(II)–NO) involves the transient ferric nitrosylated species (Mb(III)–NO), followed by NO dissociation and formation of ferric myoglobin (Mb(III)). In contrast, peroxynitrite-mediated oxidation of ferrous oxygenated myoglobin (Mb(II)–O2) involves the transient ferrous deoxygenated and ferryl derivatives (Mb(II) and Mb(IV)O, respectively), followed by Mb(III) formation. Here, kinetics of peroxynitrite-mediated oxidation of ferrous carbonylated horse heart myoglobin (Mb(II)–CO) is reported. Values of the first-order rate constant for peroxynitrite-mediated oxidation of Mb(II)–CO (i.e., for Mb(III) formation) and of the first-order rate constant for CO dissociation from Mb(II)–CO (i.e., for Mb(II) formation) are h = (1.2 ± 0.2) × 10−2 s−1 and koff(CO) = (1.4 ± 0.2) × 10−2 s−1, respectively, at pH 7.2 and 20.0 °C. The coincidence of values of h and koff(CO) indicates that CO dissociation represents the rate limiting step of peroxynitrite-mediated oxidation of Mb(II)–CO.