The interaction of short chain coenzyme Q analogs with different redox states of myoglobin

Two equivalent oxidation of metmyoglobin (Mb(III)) by hydrogen peroxide (H2O2) yields an oxoferryl moiety (Mb(IV)) plus a protein radical which presumably originates from the conversion of tyrosines to tyrosyl radicals (.Mb(IV)). In the absence of electron donors, Mb(III) oxidation is followed by (i) heme degradation or (ii) tyrosyl radical-dependent reactions, such as irreversible dimerization or covalent binding of the heme group to the apoprotein. Moreover, the oxidizing equivalents of H2O2-activated Mb(III) promote the peroxidative decomposition of polyunsaturated fatty acids. In this study, water soluble short chain coenzyme Q analogs (CoQ(1)H(2) and CoQ(2)H(2)) were found to reduce the oxoferryl moiety, preventing heme degradation and regenerating Mb(III) and, more slowly, Mb(II)O(2). CoQ(1)H(2) and CoQ(2)H(2) were also found to reduce tyrosyl radicals generated by UV irradiation of tyrosine solutions. Accordingly, CoQ(1)H(2) and CoQ(2)H(2) effectively prevented tyrosyl radical-dependent reactions such as the dimerization of sperm whale myoglobin and heme-apoprotein covalent binding in horse heart myoglobin. By competing for the oxidizing equivalents of hypervalent myoglobin, CoQ(1)H(2) and CoQ(2)H(2) also prevented the peroxidation of arachidonic acid. Collectively, these studies suggest that the proposed function of coenzyme Q as a naturally occurring antioxidant might well relate to its ability of reducing H2O2-activated myoglobin. Coenzyme Q should therefore mitigate cardiac or muscular dysfunctions that are caused by an abnormal generation of H2O2.