Many toxic xenobiotics appear to be either strong electrophiles or capable of producing strong electrophiles in the body. The reaction of these electrophiles with critical body nucleophiles triggers the sequence of biochemical changes which ultimately produce tissue damage. Conjugation with glutathione represents the body's first line of defense against toxic electrophiles. The glutathione S-transferases are the enzymes which are responsible for catalyzing these reactions and hence play a key role in the protection of tissues against damage by electrophiles. The objective of the proposed studies is to examine in a systematic fashion the stereochemical aspects and mechanisms of some of the conjugation features of foreign compounds which enhance their ability to act as substrates for these enzymes. We will examine the stereochemical aspects of the conjugation of Beta-methyl styrene oxide isomers and the substitution reactions of l-substituted ethyl benzenes and 2-substituted octanes catalyzed by rat liver glutathione S-transferase isozymes. We will also examine the stereochemical aspects of the metabolism of l-chloroethyl benzene in vivo.
| Marchand, D H; Remmel, R P; Abdel-Monem, M M (1988) Biliary excretion of a glutathione conjugate of busulfan and 1,4-diiodobutane in the rat. Drug Metab Dispos 16:85-92 |
| Ridgewell, R E; Abdel-Monem, M M (1987) Stereochemical aspects of the glutathione S-transferase-catalyzed conjugations of alkyl halides. Drug Metab Dispos 15:82-90 |
| Remmel, R P; Amoh, K; Abdel-Monem, M M (1987) The disposition and pharmacokinetics of ketoconazole in the rat. Drug Metab Dispos 15:735-9 |
| Mishra, N C; Estensen, R D; Abdel-Monem, M M (1986) Isolation and purification of phorbol from croton oil by reversed-phase column chromatography. J Chromatogr 369:435-9 |
| Marchand, D H; Abdel-Monem, M M (1985) Glutathione S-transferases catalyzed conjugation of 1,4-disubstituted butanes with glutathione in vitro. Biochem Biophys Res Commun 128:360-7 |
