title: Regeneration of the antioxidant ubiquinol by lipoamide dehydrogenase, thioredoxin reductase and glutathione reductase.
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.
authors.affiliation: Department of Laboratory Medicine, F 46, Karolinska Institutet, Huddinge University Hospital, SE-141 86 Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Nordman
authors.forename: Ling
authors.initials: L
authors.lastname: Xia
authors.forename: Linda
authors.initials: L
authors.lastname: Björkhem-Bergman
authors.forename: Anastassios
authors.initials: A
authors.lastname: Damdimopoulos
authors.forename: Ivan
authors.initials: I
authors.lastname: Nalvarte
authors.forename: Elias S J
authors.initials: ES
authors.lastname: Arnér
authors.forename: Giannis
authors.initials: G
authors.lastname: Spyrou
authors.forename: Lennart C
authors.initials: LC
authors.lastname: Eriksson
authors.forename: Mikael
authors.initials: M
authors.lastname: Björnstedt
authors.forename: Jerker M
authors.initials: JM
authors.lastname: Olsson
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D008058:Dihydrolipoamide Dehydrogenase / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D008058:Dihydrolipoamide Dehydrogenase; D005980:Glutathione Reductase; D013880:Thioredoxin-Disulfide Reductase; C003741:ubiquinol