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.
Xia
L
L
Department of Microbiology, Pathology and Immunology, Division of Pathology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
Björnstedt
M
M
Nordman
T
T
Eriksson
L C
LC
Olsson
J M
JM
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