Inhibition of human glutathione S-transferases by bile acids

Glutathione S-transferase (GST) isoenzymes isolated from various human tissues are differentially inhibited by bile acids. Trihydroxy bile acid (lithocholate) was found to be more inhibitory to all the human GST isoenzymes tested in this study, as compared to the monohydroxy (cholate) and dihydroxy (chenodeoxycholate) bile acids. Among the three major classes of GST, mu class isoenzymes are generally inhibited to a greater extent than the alpha and pi class isoenzymes. The results of this study also indicate that differential inhibition of GST by various bile acids may be used to distinguish closely related GST isoenzymes within the mu class of GST isoenzyme. Likewise, the pi class or the anionic isoenzymes of human kidney, placenta, and erythrocytes can be distinguished using bile acid inhibition studies. These studies also provide further support for tissue-specific expression of GST isoenzymes in humans.