{"id":"9f4c7993-e253-56e4-b36e-31f6ebd4e8c3","stable_key":"db0fc92e-b5ef-5667-a4c5-3ef257edbc9b:glutathione-acetaminophen-napqi","predicate":"forms_via_p450_oxidation","statement":"Cytochrome-P450-mediated acetaminophen oxidation produced NAPQI in the experimental oxidation system.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"a879ec18-19a2-5871-8f1d-ebb6429c27b4","mechanism_event_label":"The parent drug and its reactive metabolite are separate chemical entities.","subject":{"id":"a901be21-7915-543c-ac67-c39ef72b0d03","slug":"acetaminophen","display_name":"Paracetamol","entity_type_key":"drug"},"object":{"id":"43887d3e-e850-568f-9585-659c5561b3a7","slug":"napqi","display_name":"N-Acetyl-p-benzoquinone imine / NAPQI","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"a879ec18-19a2-5871-8f1d-ebb6429c27b4","stable_key":"db0fc92e-b5ef-5667-a4c5-3ef257edbc9b:glutathione-acetaminophen-napqi-event","event_type":"biochemical_relationship","label":"The parent drug and its reactive metabolite are separate chemical entities.","description":"Cytochrome-P450-mediated acetaminophen oxidation produced NAPQI in the experimental oxidation system.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a901be21-7915-543c-ac67-c39ef72b0d03","slug":"acetaminophen","display_name":"Paracetamol","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"43887d3e-e850-568f-9585-659c5561b3a7","slug":"napqi","display_name":"N-Acetyl-p-benzoquinone imine / NAPQI","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/glutathione-research/6424115.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08\", \"start_char\": 0, \"end_char\": 1307, \"text_sha256\": \"8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Enzyme oxidation and radiolabeled binding assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"NAPQI or acetaminophen with reductants","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Experimental chemistry; no new human dose threshold or treatment regimen is inferred.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Glutathione research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Mouse microsomes and cell-free cytochrome-P450 system","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The parent drug and its reactive metabolite are separate chemical entities.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[glutathione-p6424115] N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. (1984). https://pubmed.ncbi.nlm.nih.gov/6424115/ DOI: 10.1073/pnas.81.5.1327","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Acetaminophen reactive-metabolite handling","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"460a5312-4d01-5f7c-97ef-75fb9984f37b","evidence_kind":"source_excerpt","locator":"Lines 1048-1059","start_line":1048,"end_line":1059,"excerpt":"### glutathione-acetaminophen-napqi\nCytochrome-P450-mediated acetaminophen oxidation produced NAPQI in the experimental oxidation system.\nCondition category: normal\nnutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The parent drug and its reactive metabolite are separate chemical entities.\norganism: Mouse microsomes and cell-free cytochrome-P450 system\ntissue_or_cell_type: Acetaminophen reactive-metabolite handling\nexperimental_model: Enzyme oxidation and radiolabeled binding assays\nlimitations: Experimental chemistry; no new human dose threshold or treatment regimen is inferred.\nexposure: NAPQI or acetaminophen with reductants\nevidence_span: {\"source_cache\": \"artifacts/glutathione-research/6424115.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08\", \"start_char\": 0, \"end_char\": 1307, \"text_sha256\": \"8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08\"}\n[glutathione-p6424115] N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. (1984). https://pubmed.ncbi.nlm.nih.gov/6424115/ DOI: 10.1073/pnas.81.5.1327","model_system":"Enzyme oxidation and radiolabeled binding assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [glutathione-p6424115] N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. (1984). https://pubmed.ncbi.nlm.nih.gov/6424115/ DOI: 10.1073/pnas.81.5.1327","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"9b7417fd-059d-5683-b452-71d1e3cf82d0","stable_key":"import-db0fc92e-b5ef-5667-a4c5-3ef257edbc9b","title":"Glutathione: metabolism, signaling and nutrient connections (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"2a5740c4a7e770aafe883fea47909b18bf5e174f211749935130a50f9dea2753","revision_id":"a64016dd-4b72-5954-a72d-0e61de854073","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}