REGIOSPECIFIC REDUCTION OF POLYCYCLIC AROMATIC QUINONES BY RABBIT LIVER DIHYDRODIOL DEHYDROGENASES

Dihydrodiol dehydrogenase (DDH) isoenzymes were purified from rabbit l iver (Klein et al., Eur. J. Biochem., 205 (1992) 1155), and the major forms CF-1, CF-5 and CM-2 were tested for their substrate specificity with dihydrodiol and quinone metabolites of polycyclic aromatic hydroc arbons. CF-5, which was shown to correspond to aldehyde reductase in r abbit liver, was found to efficiently oxidize aromatic dihydrodiol met abolites (phenanthrene-1,2-dihydrodiol, benz[a]anthracene-3,4-dihydrod iol) while CF-1, corresponding to carbonyl reductase, and CM-2 were mu ch less active. All three enzyme forms were found to reduce polycyclic K-region o-quinones of benz[a]anthracene, chrysene and benzo[a]pyrene . CF-1 was the least active, and CM-2 was the most active form with re action velocities of > 10 mumol/min - mg protein. Among a range of syn thetic quinones tested, benz[a]anthracene-8,9-quinone and benzo[a]pyre ne 9,10-quinone were also good substrates for the three enzymes, as we ll as p-benzoquinone and naphthalene-1,4-quinone. The reduction of pol ycyclic o-quinones, but not of p-benzoquinone, by enzyme CM-2 was acco mpanied by the oxidation of large amounts of NADPH and the consumption of molecular oxygen which is indicative of a redox-cycling process. T hus, the formation of catechol metabolites from dihydrodiols and o-qui nones may be catalyzed by the same enzymes in rabbit liver, and the re action rate of the enzymatic reduction is strongly dependent on the st ructural type of the polycyclic quinone.