Study on Dihydrodiol Dehydrogenase (I) Molecular Forms of the Enzyme and the Presence of a Dihydrodiol Specific Enzyme in Bovine Liver Cytosol
It has been known that benzo(a)pyrene and benzo(a)anthracene, typical carcinogenic polycyclic aromatic hydrocarbons, are metabolized in microsome to the corresponding dihydrodiols via epoxides (Yang, et al., 1976; Thakker, et al., 1982) and then converted to the ultimate carcinogens (Buening, et al., 1978). Dihydrodiol dehydrogenase is an enzyme which catalyzes the dehydrogenation of the dihydrodiols of benzo(a)pyrene and benzo(a)anthracene in the presence of NADP+ and forms o-quinone (Vogel, et al., 1980; Smithgall, et al., 1988). The addition of this enzyme to the Ames test significantly reduced the mutagenicity of benzo(a)pyrene, suggesting that this enzyme might detoxify the trans-dihydrodiols which were formed in situ by oxidizing them to the less reactive o-quinones (Glatt, et al., 1979). In addition, similar experiments showed that the purified enzyme reduced the mutagenicity of other polycyclic aromatic hydrocarbons (Smithgall, et al., 1986). On the basis of these facts, Penning and coworkers suggested that dihydrodiol/ 3α -hydroxysteroid dehydrogenase might play an important role in the detoxification of these carcinogenic polycyclic aromatic hydrocarbons in rat liver (Smithgall, et al., 1988). Recently, many dihydrodiol dehydrogenases were purified from various animals and tissues, and these enzymes were identified as 3α -hydroxysteroid dehydrogenase, 17β -hydroxysteroid dehydrogenase and aldehyde reductase from their substrate specificities and inhibitor sensitivities (Smithgall, et al., 1988; Sawada, et al., 1988; Terada, et al., 1990).
KeywordsPolycyclic Aromatic Hydrocarbon Bovine Liver Hydroxysteroid Dehydrogenase Aldehyde Reductase Inhibitor Sensitivity
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- Bergmeyer,H.U.,Gawehn,K.,Grassl,M., 1974, Enzymes as biochemical reagent. in: “Methods of Enzymatic Analysis,” H.U.Bergmeyer ed., Verlag Chemie Weinheim Academic Press,Inc. New York and LondonGoogle Scholar
- Buening,M.K., Wislocki,P.G., Levin,W., Yagi,H., Thakker,D.R., Akagi,H., Koreeda,M.,Jerina,D.M.and Conney.A.H., 1978, Tumorigenicity of the optical enantiomers of the diasteromeric benzo(a)pyrene 7,8-diol-9,10-epoxides in newborn mice: Experimental activity of (+)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, Proc. Natl. Acad. Sci. USA, 75: 5358PubMedCrossRefGoogle Scholar
- Phillips,A.H. and Llandon,R.G.,1962, Hepatic triphosphopyridine nucleotide cytochrome c reductase : Isolation, characterization, and kinetic studies, J.Biol.Chem.,237: 2656Google Scholar
- Piatt,K.L.,Oesch,F.,1977,An improved synthesis of trans-5,6-dihydroxy-l,3-1,3-cyclohexidine(trans-1,2-dihydroxy-l,2-dihydrobenzene), Synthesis, 7: 449Google Scholar
- Terada,T., Shinagawa,K., Umemura,T., Nishinaka,T., Nanjo,H., Hosomi,S.,Google Scholar
- Mizoguchi,T. and Nishihara,T., Study on dihydrodiol dehydrogenase (II) Modulation of the enzyme activity by biological disulfides, Enzymology and molecular biology of carbonyl metabolism, in press.Google Scholar
- Thakker,D.R., Levin,W., Yagi,H., Tada,M.,Ryan,D.E.,Thomas,P.E.,Conney,A.H. and Jerina,D.W.,1982, Stereoselective metabolism of the (+)- and (-)-enantiomers of trans-3,4-dihydroxy-3,4-dihydrobenz(a)anthracene by rat liver microsomes and by a purified and reconstituted cytochrome P-450 system, J.Biol.Chem., 257: 5103PubMedGoogle Scholar
- Yang, S.K., McCourt, D.W., Roller, P.P. and Gelboin,H.V., 1976, Enzymic conversion of benzo(a)pyrene leading predominantly to the diolepoxide r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene through a single enantiomer of r-7,t-8-dihydroxy-7,8-dihydrobenzo(a)-pyrene, Proc. Natl. Acad. Sci. USA,73: 2594PubMedCrossRefGoogle Scholar