Binding of paracetamol metabolites to mouse liver glutathione S-transferases.
In mouse liver homogenate with an intact microsomal metabolism covalent binding of [14C]-paracetamol amounted to 1 nmol/mg protein. 65% of the total radioactivity were bound to soluble protein and 35% to microsomes. In the soluble fraction the major radioactivity peak co-chromatographed with glutathione S-transferase activity on Sephacryl S-300. Two different minor labelled fractions with apparent molecular weights of 130 000 and 25 000 daltons were also found. In a second experiment in a reconstituted system of microsomes and supernatant, 86% of the radio-activity was bound to supernatant and 14% by of microsomes. Following ion exchange chromatography of the supernatant on DEAE-Sepharose, the two major radioactivity-containing fractions coincided with GSH-S-transferase activities, but not with selenium-dependent or non-selenium-dependent glutathione peroxidase. The data show that irreversible binding of paracetamol metabolites in mouse liver occurs preferentially to GSH-S-transferases.
D000082:Acetaminophen / Q000378:metabolism*; D000818:Animals; D005982:Glutathione Transferase / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding
D000082:Acetaminophen; D005982:Glutathione Transferase