Stereoselectivity of naphthalene epoxidation by mouse, rat, and hamster pulmonary, hepatic, and renal microsomal enzymes.
Previous studies have demonstrated the formation of three glutathione conjugates during the hepatic and pulmonary microsomal metabolism of naphthalene in the presence of reduced glutathione and cytosolic enzymes containing the glutathione transferases. These glutathione conjugates now have been identified by negative ion fast atom bombardment mass spectrometry, by proton NMR spectroscopy, and by chemical synthesis from the (1S,2R)- and (1R, 2S)-naphthalene 1,2-oxide enantiomers as isomeric hydroxyglutathionyldihydronaphthalene derivatives. All three glutathione adducts yielded prominent mass spectral ions at m/z 450 (M-H)-, 432 (dehydration product), and 306 (glutathionyl moiety) which were consistent with the monoglutathionyl derivatives of hydroxydihydronaphthalene. Signals in the proton NMR spectra at 3.60 and 4.95 ppm (adduct 1) and 3.60 and 4.95 ppm (adduct 2) indicated that these conjugates were diastereomers of 1-hydroxy-2-glutathionyl-1,2-dihydronaphthalene. Corresponding signals for H1 and H2 at 4.22 and 4.45 ppm for adduct 3 showed that this isomer was generated from attack of glutathione at the 1 position of the naphthalene 1,2-oxide. Incubation of synthetic (1S, 2R)-naphthalene 1,2-oxide with glutathione in the presence of glutathione transferases resulted in the formation of adducts 1 and 3 in approximately equal proportions; under identical conditions, glutathione conjugate 2 was formed from (1R, 2S)-naphthalene 1,2-oxide. Incubation of naphthalene, glutathione, and glutathione transferases with pulmonary, hepatic, or renal microsomal preparations from mouse, rat, and hamster resulted in the formation of all three glutathione conjugates. Substantial differences in the rates of formation of the individual conjugates were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D004852:Epoxy Compounds / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008647:Mesocricetus; D051379:Mice; D008861:Microsomes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D009281:Naphthalenes / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013237:Stereoisomerism
D004852:Epoxy Compounds; D009281:Naphthalenes; C031721:naphthalene; D005978:Glutathione