Hydrogen peroxide plays a key role in the oxidation reaction of myoglobin by molecular oxygen. A computer simulation

Abstract

The stability properties of the iron(II)-dioxygen bond in myoglobin and hemoglobin are of particular importance, because both proteins are oxidized easily to the ferric met-form, which cannot be oxygenated and is therefore physiologically inactive. In this paper, we have formulated all the possible pathways leading to the oxidation of myoglobin to metmyoglobin with each required rate constant in 0.1 M buffer (pH 7.0) at 25 degrees C, and have set up six rate equations for the elementary processes going on in a simultaneous way. By using the Runge-Kutta method to solve these differential equations, the concentration progress curves were then displayed for all the reactive species involved. In this complex reaction, the primary event was the autoxidation of MbO2 to metMb with generation of the superoxide anion, this anion being converted immediately and almost completely into H2O2 by the spontaneous dismutation. Under air-saturated conditions (PO2 = 150 Torr), the H2O2 produced was decomposed mostly by the metMb resulting from the autoxidation of MbO2. At lower pressures of O2, however, H2O2 can act as the most potent oxidant of the deoxyMb, which increases with decreasing O2 pressures, so that there appeared a well defined maximum rate in the formation of metMb at approximately 5 Torr of oxygen. Such examinations with the aid of a computer provide us, for the first time, with a full picture of the oxidation reaction of myoglobin as a function of oxygen pressures. These results also seem to be of primary importance from a point of view of clinical biochemistry of the oxygen supply, as well as of pathophysiology of ischemia, in red muscles such as cardiac and skeletal muscle tissues.

Kinetic and mechanistic studies of the reactions of nitrogen monoxide and nitrite with ferryl myoglobin

“…The second-order rate constants (k 3 ), obtained from the linear plots of the observed pseudo-first-order rate constants versus nitrite concentration (data not shown), are highly pH dependent (Table 3). At pH 6.1 we obtained k 3 =(3.7 [46,47,48]. This instability did not cause any problems for the determination of the rate constant of the reaction with NO´because this latter reaction proceeds at a significantly faster rate.…”

“…As the reaction of MbFe IV =O with nitrite is very slow and the MbFe IV =O solutions are not indefinitely stable [46,47,48], it proved impossible to determine the yield of the nitrite-mediated reduction of MbFe IV =O. Indeed, the reaction of one equivalent of nitrite with MbFe IV =O is slower than the autoreduction of MbFe IV =O to metMb.…”

Reactions of Sperm Whale Myoglobin with Hydrogen Peroxide

“…The reason for this increased stability is the ϳ4-fold greater rate of autoreduction of the H64Q/L29F ferryl intermediate (k 2 ), which enhances the removal of HOOH by the peroxidative cycle. Although the H64Q/L29F double mutant has a similar initial rate of autoxidation, the mutant metmyoglobin formed is a 4-fold better catalyst for removing the resultant HOOH, which ordinarily would accelerate the oxidation process as described previously (43). Thus, the H64Q/L29F combination produces a myoglobin that is significantly more resistant to HOOH damage without altering significantly its oxygen binding properties and initial rate of autoreduction.…”

The Globin-based Free Radical of Ferryl Hemoglobin Is Detected in Normal Human Blood

“…Hydrogen peroxide can also react directly with deoxyhemoglobin (10,54), resulting in the ferryl form (reaction 6), which either comproportionates with oxyhemoglobin (10) (reaction 7) or undergoes reduction to metHb via a first order reaction (reaction 8) (21,58). The autoreduction of the free radicals, which causes radical decay after H 2 O 2 is exhausted (Fig.…”