Reduction of ubiquinone by lipoamide dehydrogenase. An antioxidant regenerating pathway.
Lipoamide dehydrogenase belongs to a family of pyridine nucleotide disulfide oxidoreductases and is ubiquitous in aerobic organisms. This enzyme also reduces ubiquinone (the only endogenously synthesized lipid-soluble antioxidant) to ubiquinol, the form in which it functions as an antioxidant. The reduction of ubiquinone was linear with time and exhibited turnover numbers of 5 and 1.2 min(-1) in the presence and absence of zinc, respectively. The reaction was stimulated by zinc and cadmium but not by the other divalent ions tested. The zinc/cadmium-dependent stimulation of the reaction increased rapidly and linearly up to a concentration of 0.1 mM and was even further increased at 0.5 mM. At pH 6, the activity was three times higher than at physiological pH. Alteration of the NADPH : NADP(+) ratio revealed that the reaction is inhibited by higher concentrations of the oxidized cofactors. FAD reduced ubiquinone in a dose-dependent manner at a considerably lower rate, suggesting that the reduction of ubiquinone by lipoamide dehydrogenase involves the FAD moiety of the enzyme.
Department of Microbiology, Pathology and Immunology, Division of Pathology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
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L
Xia
M
M
Björnstedt
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T
Nordman
L C
LC
Eriksson
J M
JM
Olsson
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism*; D002104:Cadmium / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003067:Coenzymes / Q000378:metabolism*; D008058:Dihydrolipoamide Dehydrogenase / Q000378:metabolism*; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D006321:Heart; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D015227:Lipid Peroxidation; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D013552:Swine; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism
D000975:Antioxidants; D002413:Cations, Divalent; D003067:Coenzymes; D002104:Cadmium; D009243:NAD; D014451:Ubiquinone; D005182:Flavin-Adenine Dinucleotide; D009249:NADP; D008058:Dihydrolipoamide Dehydrogenase; C025204:Ubiquinone Q2; D015032:Zinc; C003741:ubiquinol