Antioxidant-derived prooxidant formation from ubiquinol.
Ubiquinol (QH2) 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 QH2 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 H2O2 by spontaneous dismutation. SQ* not involved in autoxidation may react with H2O2. Transfer of the odd electron to H2O2 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, QH2 and vitamin E were equally effective in scavenging lipid radicals; the radical protecting activity of QH2 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.
Nohl
H
H
Institute of Pharmacology and Toxicology, Veterinary University of Vienna, Austria. Hans.Nohl@VU-WIEN.AC.AT
Gille
L
L
Kozlov
A V
AV
D000975:Antioxidants / Q000378:metabolism*; D016227:Benzoquinones / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005682:Gadolinium / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D008081:Liposomes / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism*; D010545:Peroxides / Q000378:metabolism; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism; D014466:Ultraviolet Rays; D014810:Vitamin E / Q000378:metabolism
D000975:Antioxidants; D016227:Benzoquinones; D016166:Free Radical Scavengers; D005609:Free Radicals; D008081:Liposomes; D016877:Oxidants; D010545:Peroxides; D013113:Spin Labels; D013481:Superoxides; D014451:Ubiquinone; D014810:Vitamin E; C025232:semiquinone radicals; D017665:Hydroxyl Radical; D005682:Gadolinium; D006861:Hydrogen Peroxide; C003741:ubiquinol