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.

Fibrates but not statins increase plasma selenium in dyslipidemic aged patients – The EVA study

“…Moreover, coenzyme Q10 depletion during statin therapy [29,30] might be associated with selenium deficiency. Indeed, it has been reported that the ubiquinol-10 is regenerated by selenoenzyme [31,32]. As regard fibrates, several hypothesis might explain the beneficial effect on plasma selenium concentrations.…”

Selenium and coenzyme Q10 interrelationship in cardiovascular diseases – A clinician's point of view

“…Selenium in the form of the selenoprotein TrxR1 , which contains a unique amino acid, the selenocysteine (SeC), in its active site, is needed for the cell to reduce coenzyme Q10 (ubiquinone) to the active form ubiquinol [54,55]. Also, the synthesis of the SeC-containing proteins requires a functional mevalonate pathway, where coenzyme Q10 is a product [32].…”

Direct and indirect antioxidant properties of inducers of cytoprotective proteins

“…Tocopherols then act as chain-breaking antioxidants inhibiting the propagation of lipid peroxidation [45]. At least three members of the cytoprotective phase 2 response, all of them FADdependent flavoproteins, participate in the regeneration of ubiquinols from their oxidized forms: NQO1 [46,47], thioredoxin reductase, and glutathione reductase [48]. In additions, NQO1 also plays a role in regenerating the reduced and active form of the antioxidant alpha-tocopherolhydroquinone [49,50].…”