TY - JOUR T1 - Stereochemical aspects of the glutathione S-transferase-catalyzed conjugations of alkyl halides. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 82 LP - 90 VL - 15 IS - 1 AU - R E Ridgewell AU - M M Abdel-Monem Y1 - 1987/01/01 UR - http://dmd.aspetjournals.org/content/15/1/82.abstract N2 - (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. ER -