title: Stereospecific glutathione conjugation of (R)- and (S)-2-bromoisovalerylurea in freshly isolated rat kidney proximal tubular cells.
abstract: The glutathione conjugation of 2-bromoisovalerylurea (BIU) was studied in isolated proximal tubular kidney cells of the rat. Racemic (R,S)-BIU was incubated with the cell suspension, and the incubation medium was analysed for the diastereomeric glutathione (GSH) conjugates, cysteine conjugates and mercapturates that can be formed from (R)- and (S)-BIU. Only the mercapturate formed from (R)-BIU was found, as well as its cysteine precursor. No GSH conjugates were detected. These results indicate that these cells conjugate only the (R)-BIU enantiomer, and that the GSH conjugate is immediately further metabolized to its cysteine conjugate and mercapturate.
authors.affiliation: Division of Toxicology, University of Leiden, Sylvius Laboratories, The Netherlands.
authors.forename: M M
authors.initials: MM
authors.lastname: Viver
authors.forename: J F
authors.initials: JF
authors.lastname: Nagelkerke
authors.forename: G J
authors.initials: GJ
authors.lastname: Mulder
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D001968:Bromisovalum / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D008968:Molecular Conformation; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
chemical_list: D001968:Bromisovalum; D005978:Glutathione; D003545:Cysteine; D000111:Acetylcysteine