Sep 1, 1987

Inhibition of human cationic glutathione S-transferase by nonsubstrate ligands

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
T D Boyer, D A Vessey


Inhibition of a major hepatic form of human cationic glutathione S-transferase by bilirubin, biliverdin, indocyanine green and chenodeoxycholic acid was investigated as a function of pH (range = 6.5 to 9.1). Changes in pH had little effect on the extent of inhibition by indocyanine green. However, inhibition by bilirubin, biliverdin and chenodeoxycholic acid was found to be pH-dependent, with markedly less inhibition at the high values of pH. The reduced inhibition at the high values of pH could not be ascribed to a failure of the enzyme to bind the nonsubstrate ligand. Instead, the complete inhibition observed at pH 6.5 became partial (hyperbolic) inhibition at pH 9.1. This behavior can be ascribed to the binding of the nonsubstrate ligands at a site other than the active site, i.e., at high values of pH there is formation of an enzyme-substrate-inhibitor complex which still retains considerable catalytic activity. At physiologic values of pH (7.0), the human transferase was completely inhibited by saturating concentrations of the tested nonsubstrate ligands. This is in contrast to our previous studies performed with the rat transferases where, although inhibition also was affected by buffer pH, some forms of the enzyme retain...Continue Reading

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Mentioned in this Paper

Enzymes, antithrombotic
Chenodeoxycholic Acid
Bilirubin, (4E,15E)-Isomer
Serum Bilirubin Measurement
Metabolic Detoxication, Drug
Biliverdin IX alpha

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