ANTIOXIDANT-DERIVED PROOXIDANT FORMATION FROM UBIQUINOL

Ubiquinol (QH(2)) is increasingly used as antioxidant for the treatmen t of a variety of diseases and the modulation of biological aging; how ever, the biological significance of secondary reaction products has b een disregarded so far. Our studies on the antioxidant activity of ubi quinol in peroxidizing lipid membranes demonstrate the existence of ub isemiquinone (SQ(.)) as the first reaction product of ubiquinol. A fra ction of SQ(.) derived from the antioxidative activity of QH(2) was de tected in the outer section of the membrane bordering the aqueous phas e. This localization allows an access of protons and water from the aq ueous phase to SQ(.) a prerequisite earlier found to trigger autoxidat ion. Superoxide radicals emerging from this fraction of autoxidizing S Q(.) form H2O2 by spontaneous dismutation. SQ(.) not involved in autox idation may react with H2O2. Transfer of the odd electron to H2O2 resu lted in HO. and HO- formation by homolytic cleavage. An analogous reac tion was also possible with lipid hydroperoxides which accumulate in b iological membranes during lipid peroxidation. The reaction products e merging from this reaction were alkoxyl radicals. Both HO. and alkoxyl radicals are strong initiators and promoters of lipid peroxidation. I ndirect evidence of the existence and prooxidative activities of these secondary reaction products came from comparative studies with vitami n E. While in the absence of other reactants, QH(2) and vitamin E were equally effective in scavenging lipid radicals; the radical protectin g activity of QH(2) was found to be significantly lower as compared to vitamin E when these antioxidants operate in peroxidizing lipid membr anes. This discrepancy reveals that the antioxidative activity of coen zyme Q is compulsorily linked to the formation of split products count eracting the membrane protective effect of this natural antioxidant. ( C) 1998 Elsevier Science Inc.