THE INTERACTION OF SHORT-CHAIN COENZYME-Q ANALOGS WITH DIFFERENT REDOX STATES OF MYOGLOBIN

Two equivalent oxidation of metmyoglobin (Mb(III)) by hydrogen peroxid e (H2O2) yields an oxoferryl moiety (Mb(IV)) plus a protein radical wh ich presumably originates from the conversion of tyrosines to tyrosyl radicals (.Mb(IV)). In the absence of electron donors, Mb(III) oxidati on is followed by (i) heme degradation or (ii) tyrosyl radical-depende nt 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 p olyunsaturated fatty acids. In this study, water soluble short chain c oenzyme 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 fo und to reduce tyrosyl radicals generated by UV irradiation of tyrosine solutions. Accordingly, CoQ(1)H(2) and CoQ(2)H(2) effectively prevent ed tyrosyl radical-dependent reactions such as the dimerization of spe rm 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 o f arachidonic acid. Collectively, these studies suggest that the propo sed function of coenzyme Q as a naturally occurring antioxidant might well relate to its ability of reducing H2O2-activated myoglobin. Coenz yme Q should therefore mitigate cardiac or muscular dysfunctions that are caused by an abnormal generation of H2O2.