Peroxidative interaction of myoglobin and myosin

Met-myoglobin [Fe(III)] was found to induce myosin cross-linking in the presence of H2O2 [Bhoite-Solomon, V. & Shaklai, N. (1992) Biochem. Int. 26, 181-189]. To assess the relevance of these findings to cellular pathology, peroxidation of myosin was performed with physiological divalent iron [Fe(II)] myoglobins in the oxy and deoxy forms. Both myoglobin forms were capable of mediating cross-linking of myosin. Deoxymyoglobin reactivity was similar to that of met-myoglobin, but the reactivity of oxymyoglobin was retarded compared to deoxymyoglobin. Cross-linking of myosin occurred under a low flow rate of H2O2 (3 microM/min) and in the presence of excess oxymyoglobin over H2O2, known to diminish the steady state of the myoglobin active heme [ferryl, Fe(IV)]state. The adenosinetriphosphatase activity of myosin was reduced to about half due to cross-linking. Addition of myoglobin/H2O2 to high myosin concentrations (> = 20 microM) turned the solutions into gels, a phenomenon explained by the further formation of intermolecular super cross-links of soluble myosin. Thus, at cellular ionic strength in which myosin is insoluble, cross-linking of myosin could still be triggered by myoglobin and H2O2. Based on these data, it is suggested that myoglobin-induced cross-linking of myosin and the consequent loss of adenosinetriphosphatase activity may be involved in muscle malfunction under hypoxia when cellular peroxidants increase and the deoxymyoglobin form prevails.