Affiliations: Molecular Pharmacology and Toxicology Unit, Department
of Natural Sciences, University of Veterinary Medicine Vienna, Vienna,
Austria | Department of Clinical Pharmacy and Diagnostics,
University of Vienna, Vienna, Austria | Department of Pharmacognosy, University of Vienna,
Vienna, Austria | Research and Development, DSM Nutritional Products,
Basel, Switzerland | Department of Chemistry, University of Natural
Resources and Applied Life Sciences, Vienna, Austria
Note: [] Address for correspondence: Dr. Lars Gille, Molecular
Pharmacology and Toxicology Unit, Department of Natural Sciences, University of
Veterinary Medicine Vienna, Veterinärplatz 1, A-1210 Vienna, Austria.
Tel.: +43 1 25077 4407; Fax: +43 1 25077 4490; E-mail:
Lars.Gille@vu-wien.ac.at
Abstract: Ubichromanol-9 (UCa_{9}), with a side chain
consisting of nine isoprene units) is a reductive cyclization product of
ubiquinone-10 (UQ_{10}). It acts as a radical scavenging
antioxidant and is about half as effective as α-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 (UQ_{10}OH), 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 bc_{1}
complex) was slightly below that of native ubiquinol, but significantly higher
than that of reduced α-tocopheryl quinone. Since ubiquinone-like
molecules (UQ_{10}OH, UQ_{10}) were
identified as oxidation products of UCa_{9} during lipid
peroxidation, this ubiquinone derivative could provide a possibility to combine
antioxidant properties of chromanols and bioenergetic benefits of
UQ_{10}.
