title: Ubichromanol: a prodrug to support mitochondrial ubiquinone functions?
abstract: Ubichromanol-9 (UCa9), with a side chain consisting of nine isoprene units) is a reductive cyclization product of ubiquinone-10 (UQ10). It acts as a radical scavenging antioxidant and is about half as effective as alpha-tocopherol. Already decades ago its one-electron oxidation product, the ubichromanoxyl radical had been identified. However, nothing was known so far about the two-electron oxidation product of this antioxidant and its bioactivity. This study proves that ubichromanol can be oxidized to a ubiquinone-like compound with a hydroxyl-substituted side chain (UQ10OH), a metabolite that is naturally present in bovine liver mitochondria. The bioactivity of this ubiquinone derivative in its reduced form as substrate for mitochondrial complex III (cytochrome bc1 complex) was slightly below that of native ubiquinol, but significantly higher than that of reduced alpha-tocopheryl quinone. Since ubiquinone-like molecules (UQ10OH, UQ10) were identified as oxidation products of UCa9 during lipid peroxidation, this ubiquinone derivative could provide a possibility to combine antioxidant properties of chromanols and bioenergetic benefits of UQ10.
authors.affiliation: Molecular Pharmacology and Toxicology Unit, Department of Natural Sciences, University of Veterinary Medicine Vienna, Vienna, Austria. Lars.Gille@vu-wien.ac.at
authors.forename: Lars
authors.initials: L
authors.lastname: Gille
authors.forename: Werner
authors.initials: W
authors.lastname: Stamberg
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Gregor
authors.forename: Walter
authors.initials: W
authors.lastname: Jäger
authors.forename: Gottfried
authors.initials: G
authors.lastname: Reznicek
authors.forename: Thomas
authors.initials: T
authors.lastname: Netscher
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosenau
authors.forename: Hans
authors.initials: H
authors.lastname: Nohl
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D002839:Chromans / Q000378:metabolism / Q000494:pharmacology*; D014450:Electron Transport Complex III / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007700:Kinetics; D008929:Mitochondria, Heart / Q000378:metabolism; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000975:Antioxidants; D002839:Chromans; D016166:Free Radical Scavengers; D011355:Prodrugs; C534776:ubichromanol-9; D014450:Electron Transport Complex III