Ubichromanol: a prodrug to support mitochondrial ubiquinone functions?
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.
Gille
Lars
L
Molecular Pharmacology and Toxicology Unit, Department of Natural Sciences, University of Veterinary Medicine Vienna, Vienna, Austria. Lars.Gille@vu-wien.ac.at
Stamberg
Werner
W
Gregor
Wolfgang
W
Jäger
Walter
W
Reznicek
Gottfried
G
Netscher
Thomas
T
Rosenau
Thomas
T
Nohl
Hans
H
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
D000975:Antioxidants; D002839:Chromans; D016166:Free Radical Scavengers; D011355:Prodrugs; C534776:ubichromanol-9; D014450:Electron Transport Complex III