Enantioselectivity in glutathione conjugation of 1,2-epoxy-1,2,3,4-tetrahydronaphthalene by hepatic glutathione S-transferase

Abstract

Enantiomers of 1,2-epoxy-1,2,3,4-tetrahydronaphthalene (ETN) were conjugated with glutathione (GSH) specifically at their benzylic oxiran carbons, with a marked difference in rate [(1R,2S)-(+)- < (1S,2R)-(−)-ETNs] as well as in affinity for GSH S-transferase [Km: (1S,2R)-(−)- < (1R,2S)-(+)-ETNs], in rat liver cytosol to yield two diastereomeric S-(2-hydroxy-1,2,3,4-tetrahydronaphth-1-yl)glutathiones which were separable by reverse partition hplc. Enzymatic GSH conjugation of racemic ETN occurred preferentially with the (1S,1R)-(−)-component as a result of its retarding effect on the conjugation of the (1R,2S)-(+)-counterpart, one half of which remained in enantiomerically pure form in the incubation medium when the (1S,2R)-(−)-component had been completely conjugated.