Peroxidative Interaction of Myoglobin and Myosin

Abstract

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 μM/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 μM) 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. Copyright © 1995, Wiley Blackwell. All rights reserved