Affiliations: Department of Laboratory Medicine, F 46, Karolinska
Institutet, Huddinge University Hospital, SE-141 86 Stockholm, Sweden | Department of Biosciences at Novum, Center for
Biotechnology, Karolinska Institutet, Stockholm, Sweden | Department of Medical Biochemistry and Biophysics,
Karolinska Institutet, Stockholm, Sweden
Note: [] Address for correspondence: Jerker Olsson, Department of
Laboratory Medicine, Div. of Pathology, Karolinska Institutet, Huddinge
University Hospital, SE-141 86 Stockholm, Sweden. Tel.: +46 8 585 87873; Fax:
+46 8 608 2444; E-mail: [email protected]
Abstract: Ubiquinol is a powerful antioxidant, which is oxidized in action and
needs to be replaced or regenerated to be capable of a sustained effort. This
article summarises current knowledge of extramitochondrial reduction of
ubiquinone by three flavoenzymes, i.e. lipoamide dehydrogenase, glutathione
reductase and thioredoxin reductase, belonging to the same pyridine
nucleotide-disulfide oxidoreductase family. These three enzymes are the most
efficient extramitochondrial ubiquinone reductases so far described. The
reduction of ubiquinone by lipoamide dehydrogenase and glutathione reductase is
potently stimulated by zinc and the highest rate of reduction is achieved at
acidic pH and the rates are equal with either NADPH or NADH as co-factors. The
most efficient ubiquinone reductases are mammalian cytosolic thioredoxin
reductases, which are selenoenzymes with a number of biological functions.
Reduction of ubiquinone by thioredoxin reductase is in contrast to the other
two enzymes investigated, inhibited by zinc and shows a sharp physiological pH
optimum at pH 7.5. Furthermore, the reaction is selenium dependent as revealed
from experiments using truncated and mutant forms of the enzyme and also in a
cellular context by selenium treatment of transfected thioredoxin reductase
overexpressing stable cell lines. The reduction of ubiquinone by the three
enzymes offers a multifunctional system for extramitochondrial regeneration of
an important antioxidant.
