Stereoselective conjugation of a uricosuric diuretic with glutathione by glutathione transferase 3-3.
1. The activity of glutathione (GSH) transferases in rat liver cytosol was inhibited by the (-) enantiomer of a uricosuric diuretic (6,7-dichloro-5[N,N-dimethylsulphamoyl]-2,3-dihydrobenzofuran-2-ca rboxylic acid, DBCA) in a concentration-dependent manner. Although the DBCA (+) enantiomer inhibited the activity of liver cytosol GSH transferases, it was less effective. 2. Among four purified GSH transferase isozymes obtained from rat liver cytosol, isozyme 3-3 showed stereoselective interactions with the enantiomers of DBCA. This isozyme most actively and preferentially catalysed the transfer of GSH to DBCA (-) enantiomer.
Kariya
K
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe-Gakuin University, Japan.
Okumura
H
H
Lee
E
E
Hirata
M
M
D000818:Animals; D003600:Cytosol / Q000201:enzymology; D004232:Diuretics / Q000378:metabolism* / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013449:Sulfonamides / Q000378:metabolism* / Q000494:pharmacology
D004232:Diuretics; D007527:Isoenzymes; D013449:Sulfonamides; C052960:S 8666; D005982:Glutathione Transferase; D005978:Glutathione