6533b852fe1ef96bd12ab609

RESEARCH PRODUCT

Glutathione Transferase A1-1 Catalyzed Conjugation of Polycyclic Aromatic Hydrocarbon Diol-Epoxides with Glutathione

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Abstract The glutathione transferase A1-1 (GSTA1-1) isoenzyme catalyzes the formation of GSH-conjugates of the isomeric bay-region diol-epoxides (DEs) of trans-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydrochrysene (CDE) and trans-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrodibenz[a,h]anthracene (DBADE) as well as the isomeric fjord-region DEs trans-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene (BPhDE) and trans-9,10-dihydroxy-11,12-epoxy-9,10,11,12-tetrahydro-benzo[c]chrysene (BCDE) although with an approx. 20-fold variation in catalytic efficiency. With the anti-diastereomers and the syn-diastereomers of BPhDE and BCDE, GSTA1-1 demonstrated a significant preference for the enantiomers with R-configuration at the benzylic oxirane-carbons. However, with the syn-diastereomers of the bay-region DEs (CDE and DBADE) the enantiomers with S-configuration at the benzylic oxirane-carbons were preferentially conjugated. The more chemically reactive syn-diastereomers were in general better substrates for...