Glutathione S-sulfonate, a sulfur dioxide metabolite, as a competitive inhibitor of glutathione S-transferase, and its reduction by glutathione reductase.
Glutathione S-sulfonate (GSSO3H) is a reaction product of glutathione disulfide (GSSG) and sulfite, the hydrated form of sulfur dioxide. In the present study, GSSO3H was found to be a potent competitive inhibitor of the glutathione S-transferases (GST) in the rat liver (Ki = 14 microM) and lung (Ki = 9 microM), and in human lung tumor-derived A549 cells (Ki = 4 microM). GSSO3H was also reduced by a cytosolic enzyme in the rat liver (Km = 313 microM) and lung (Km = 200 microM), and human lung A549 cells (Km = 400 microM). These results suggest that SO2 may affect the detoxification of xenobiotic compounds by inhibiting, via formation of GSSO3H, the enzymatic conjugation of glutathione (GSH) and reactive electrophiles. Although GSSO3H can be enzymatically degraded, the high substrate Km value suggests that this compound may not be readily reduced at low concentrations.
D000818:Animals; D005978:Glutathione / Q000031:analogs & derivatives* / Q000032:analysis / Q000633:toxicity; D005980:Glutathione Reductase / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013458:Sulfur Dioxide / Q000378:metabolism*
D013458:Sulfur Dioxide; C040136:glutathione sulfonate; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione