Studies of the relationship between the catalytic activity and binding of non-substrate ligands by the glutathione S-transferases.
The dimeric enzyme glutathione S-transferase B is composed of two dissimilar subunits, referred to as Ya and Yc. Transferase B (YaYc) and two other transferases that are homodimers of the individual Ya and Yc subunits were purified from rat liver. Inhibition of these three enzymes by Indocyanine Green, biliverdin and several bile acids was investigated at different values of pH (range 6.0-8.0). Indocyanine Green, biliverdin and chenodeoxycholate were found to be effective inhibitors of transferases YaYc and YcYc at low (pH 6.0) but not high (pH 8.0) values of pH. Between these extremes of pH intermediate degrees of inhibition were observed. Cholate and taurochenodeoxycholate, however, were ineffective inhibitors of transferase YcYc at all values of pH. The observed differences in bile acids appeared to be due, in part, to differences in their state of ionization. In contrast with the above results, transferase YaYa was inhibited by at least 80% by the non-substrate ligands at all values of pH. These effects of pH on the three transferases could not be accounted for by pH-induced changes in the enzyme's affinity for the inhibitor. Thus those glutathione S-transferases that contain the Yc subunit are able to act simultaneously as both enzymes and binding proteins. In addition to enzyme structure, the state of ionization of the non-substrate ligands may also influence whether the transferases can perform both functions simultaneously.
D001647:Bile Acids and Salts / Q000494:pharmacology*; D001663:Bilirubin / Q000031:analogs & derivatives*; D001664:Biliverdine / Q000494:pharmacology*; D002352:Carrier Proteins; D002384:Catalysis; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D006863:Hydrogen-Ion Concentration; D007208:Indocyanine Green / Q000494:pharmacology*; D007700:Kinetics; D008024:Ligands; D013050:Spectrometry, Fluorescence
D001647:Bile Acids and Salts; D002352:Carrier Proteins; D008024:Ligands; D002635:Chenodeoxycholic Acid; D005982:Glutathione Transferase; D005978:Glutathione; D007208:Indocyanine Green; D001664:Biliverdine; D001663:Bilirubin