Antioxidant-derived prooxidant formation from ubiquinol

Abstract

Ubiquinol (QH 2) is increasingly used as antioxidant for the treatment of a variety of diseases and the modulation of biological aging; however, the biological significance of secondary reaction products has been disregarded so far. Our studies on the antioxidant activity of ubiquinol in peroxidizing lipid membranes demonstrate the existence of ubisemiquinone (SQ ) as the first reaction product of ubiquinol. A fraction of SQ derived from the antioxidative activity of QH 2 was detected in the outer section of the membrane bordering the aqueous phase. This localization allows an access of protons and water from the aqueous phase to SQ a prerequisite earlier found to trigger autoxidation. Superoxide radicals emerging from this fraction of autoxidizing SQ form H 2O 2 by spontaneous dismutation. SQ not involved in autoxidation may react with H 2O 2. Transfer of the odd electron to H 2O 2 resulted in HO and HO − formation by homolytic cleavage. An analogous reaction was also possible with lipid hydroperoxides which accumulate in biological membranes during lipid peroxidation. The reaction products emerging from this reaction were alkoxyl radicals. Both HO and alkoxyl radicals are strong initiators and promoters of lipid peroxidation. Indirect evidence of the existence and prooxidative activities of these secondary reaction products came from comparative studies with vitamin E. While in the absence of other reactants, QH 2 and vitamin E were equally effective in scavenging lipid radicals; the radical protecting activity of QH 2 was found to be significantly lower as compared to vitamin E when these antioxidants operate in peroxidizing lipid membranes. This discrepancy reveals that the antioxidative activity of coenzyme Q is compulsorily linked to the formation of split products counteracting the membrane protective effect of this natural antioxidant.