Stereoselectivity of rat liver glutathione transferase isoenzymes for alpha-bromoisovaleric acid and alpha-bromoisovalerylurea enantiomers.
The stereoselectivity of purified rat GSH transferases towards alpha-bromoisovaleric acid (BI) and its amide derivative alpha-bromoisovalerylurea (BIU) was investigated. GSH transferase 2-2 was the only enzyme to catalyse the conjugation of BI and was selective for the (S)-enantiomer. The conjugation of (R)- and (S)-BIU was catalysed by the isoenzymes 2-2, 3-3 and 4-4. Transferase 1-1 was less active, and no catalytic activity was observed with transferase 7-7. Isoenzymes 1-1 and 2-2 of the Alpha multigene family preferentially catalysed the conjugation of the (S)-enantiomer of BIU (and BI), whereas isoenzymes 3-3 and 4-4 of the Mu multigene family preferred (R)-BIU. The opposite stereoselectivity of conjugation of BI and BIU previously observed in isolated rat hepatocytes and the summation of activities of enzymes known to be present in hepatocytes on the basis of present data are in accord.
Division of Toxicology, Sylvius Laboratories, University of Leiden, The Netherlands.
J M
JM
Te Koppele
B
B
Coles
B
B
Ketterer
G J
GJ
Mulder
D000818:Animals; D001968:Bromisovalum / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005982:Glutathione Transferase / Q000378:metabolism*; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D046911:Macromolecular Substances; D008954:Models, Biological; D008968:Molecular Conformation; D010421:Pentanoic Acids / Q000378:metabolism*; D051381:Rats; D013237:Stereoisomerism; D013379:Substrate Specificity; D014508:Urea / Q000031:analogs & derivatives*; D014631:Valerates / Q000378:metabolism*
D007527:Isoenzymes; D046911:Macromolecular Substances; D010421:Pentanoic Acids; D014631:Valerates; D001968:Bromisovalum; C057043:2-bromoisovaleric acid; D014508:Urea; D005982:Glutathione Transferase