title: Stereochemical aspects of the glutathione S-transferase-catalyzed conjugations of alkyl halides.
abstract: (R,S)-2-iodooctane and (R,S)-2-bromooctane were found to be substrates for the glutathione S-transferases from rat liver. The conjugation reactions of the enantiomeric 2-halooctanes and glutathione were found to proceed with inversion of configuration at the chiral carbon of the substrate. Selective titration of the free cysteine residues of the glutathione S-transferases provided no observable effect on the stereochemical course of these conjugation reactions. No evidence for substrate stereoselectivity was observed. The diastereomeric S-(2-octyl)glutathiones were produced in approximately equal amounts from racemic 2-halooctane substrates. With S-(+)-2-iodooctane as the electrophilic substrate, a biphasic double reciprocal plot of glutathione concentration vs. initial velocity of product formation was observed suggesting complex kinetics. The S-2-octylglutathione diastereomers were found to be potent inhibitors of the glutathione S-transferase-catalyzed conjugation of 1-chloro-2,4-dinitrobenzene. These results provide support for a single displacement mechanism for the conjugation of 2-halooctanes and glutathione catalyzed by the glutathione S-transferases with product inhibition at low glutathione concentrations.
mesh_terms: D000818:Animals; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000201:enzymology; D005982:Glutathione Transferase / Q000378:metabolism*; D006846:Hydrocarbons, Halogenated / Q000378:metabolism*; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D006846:Hydrocarbons, Halogenated; D007527:Isoenzymes; D005982:Glutathione Transferase