title: DT-diaphorase-catalyzed two-electron reduction of quinone epoxides.
abstract: DT-diaphorase catalyzes the two-electron reduction of the unsubstituted quinone epoxide, 2,3-epoxy-p-benzoquinone, at expense of NAD(P)H with formation of 2-OH-p-benzohydroquinone as the reaction product. The further conversion reactions of 2-OH-p-benzohydroquinone are influenced by the presence of O2 in the medium. Under aerobic conditions, 2-OH-p-benzohydroquinone undergoes autoxidation--probably with formation of 2-OH-semiquinone intermediates--to 2-OH-p-benzoquinone. The latter product is rapidly reduced by DT-diaphorase and, thus, its accumulation can be only observed upon exhaustion of NADPH. Under anaerobic conditions, 2-OH-p-benzohydroquinone does not undergo autoxidation and its accumulation is stoichiometrically (1:1) related to the amount of NADPH oxidized and epoxide substrate reduced. DT-diaphorase also catalyzes the reduction of the disubstituted quinone epoxide, 2,3-dimethyl-2,3-epoxy-1,4-naphthoquinone. Neither the aliphatic epoxide, trans-stilbene oxide, nor the aromatic epoxide, 4,5-epoxy-benzo[a]pyrene are substrates for DT-diaphorase. The reduction of 2,3-epoxy-p-benzoquinone is also catalyzed by the one-electron transfer enzyme, NADPH-cytochrome P450 reductase at a rate similar to that found with DT-diaphorase. However, this reaction differs from that catalyzed by DT-diaphorase in the distribution of molecular products as well as in the relative contribution of nonenzymatic reactions, i.e. semiquinone disproportionation and autoxidation.
mesh_terms: D000818:Animals; D016227:Benzoquinones; D002851:Chromatography, High Pressure Liquid; D004583:Electrons; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D009249:NADP; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D011808:Quinone Reductases / Q000378:metabolism*; D011809:Quinones / Q000378:metabolism*; D051381:Rats
chemical_list: D016227:Benzoquinones; D011809:Quinones; C054094:2,3-epoxy-1,4-benzoquinone; D009249:NADP; C054093:2-hydroxy-1,4-benzoquinone; D009251:NADPH-Ferrihemoprotein Reductase; D011808:Quinone Reductases