Enantioselectivity in glutathione conjugation of 1,2-epoxy-1,2,3,4-tetrahydronaphthalene by hepatic glutathione S-transferase.
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)-(+)- less than (1S,2R)-(-)-ETNs] as well as in affinity for GSH S-transferase [Km: (1S,2R)-(-)- less than (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,2R)-(-)-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.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D003600:Cytosol / Q000201:enzymology; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D009281:Naphthalenes / Q000378:metabolism*; D051381:Rats; D013237:Stereoisomerism; D013379:Substrate Specificity; D013764:Tetrahydronaphthalenes / Q000378:metabolism*
D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; C045789:1,2-epoxy-1,2,3,4-tetrahydronaphthalene; D005982:Glutathione Transferase; D005978:Glutathione