title: 3-Hydroxyacetaminophen: a microsomal metabolite of acetaminophen. Evidence against an epoxide as the reactive metabolite of acetaminophen.
abstract: 3-Hydroxyacetaminophen has been isolated and identified as a microsomal metabolite of acetaminophen. Analysis of the metabolite by gas chromatography-mass spectrometry revealed that the metabolite had a molecular ion and fragmentation pattern identical to that of authentic 3-hydroxyacetaminophen. Glutathione and ascorbic acid blocked covalent binding of reactive metabolite(s) to protein but did not block the formation of 3-hydroxyacetaminophen. Moreover, epoxide hydrolase did not block covalent binding of the reactive metabolite(s) to protein. Thus, the reactive metabolite apparently is not an epoxide substrate of the hydrolase, nor are 3-hydroxyacetaminophen and the reactive metabolite(s) formed from a common intermediate.
mesh_terms: D000082:Acetaminophen / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D006224:Cricetinae; D004851:Epoxide Hydrolases / Q000494:pharmacology; D004852:Epoxy Compounds / Q000378:metabolism*; D004988:Ethers, Cyclic / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D005978:Glutathione / Q000494:pharmacology; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D010100:Oxygen
chemical_list: D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D000082:Acetaminophen; D004851:Epoxide Hydrolases; D005978:Glutathione; C027361:3-hydroxyacetaminophen; D001205:Ascorbic Acid; D010100:Oxygen