DT-diaphorase-catalyzed two-electron reduction of quinone epoxides

Free Radic Biol Med. 1987;3(3):181-8. doi: 10.1016/0891-5849(87)90003-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoquinones*
  • Chromatography, High Pressure Liquid
  • Electrons
  • Kinetics
  • Liver / enzymology
  • NADP
  • NADPH-Ferrihemoprotein Reductase / metabolism
  • Oxidation-Reduction
  • Oxygen Consumption
  • Quinone Reductases / metabolism*
  • Quinones / metabolism*
  • Rats

Substances

  • Benzoquinones
  • Quinones
  • 2,3-epoxy-1,4-benzoquinone
  • NADP
  • 2-hydroxy-1,4-benzoquinone
  • NADPH-Ferrihemoprotein Reductase
  • Quinone Reductases