{"id":"79a612e2-a90c-5752-8fe6-7a491e965714","stable_key":"7de430a5-1a36-5231-b931-35cc01d8f3bf:apap-one-electron-reduction","predicate":"reduces","statement":"Reduction of prostaglandin H synthase compound II to native enzyme by phenol proceeded with a second-order rate constant of 5.3 x 10(5) per molar per second and by hydroquinone at 2.1 x 10(6), rapid scan spectra also showed reduction of compound I to compound II by both so that reduction of both compounds is a one-electron process, and the results suggest the tyrosyl radical detected in the presence of oxidizing agents is formed by intramolecular electron transfer from the tyrosyl residue to the porphyrin pi-cation radical and tends to disappear in the presence of sufficient reducing substrate.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"d347ebd8-19d8-5507-9079-c8a750f36d71","mechanism_event_label":"A phenol hands the enzyme one electron at a time, and enough of it makes the radical the enzyme needs disappear.","subject":{"id":"db2a1421-bdbf-5d98-9292-0b308f88cdfc","slug":"reducing-cosubstrate","display_name":"A reducing cosubstrate of the peroxidase","entity_type_key":"cellular_process"},"object":{"id":"e43c3122-fa3d-5d7e-9714-9707230d414c","slug":"pghs-compound-ii","display_name":"Prostaglandin H synthase compound II","entity_type_key":"protein_state"},"evidence_count":1,"mechanism_event":{"id":"d347ebd8-19d8-5507-9079-c8a750f36d71","stable_key":"7de430a5-1a36-5231-b931-35cc01d8f3bf:apap-one-electron-reduction-event","event_type":"biochemical_relationship","label":"A phenol hands the enzyme one electron at a time, and enough of it makes the radical the enzyme needs disappear.","description":"Reduction of prostaglandin H synthase compound II to native enzyme by phenol proceeded with a second-order rate constant of 5.3 x 10(5) per molar per second and by hydroquinone at 2.1 x 10(6), rapid scan spectra also showed reduction of compound I to compound II by both so that reduction of both compounds is a one-electron process, and the results suggest the tyrosyl radical detected in the presence of oxidizing agents is formed by intramolecular electron transfer from the tyrosyl residue to the porphyrin pi-cation radical and tends to disappear in the presence of sufficient reducing substrate.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c0fa302a-92e8-5be9-afc8-a386ac026b21","slug":"pghs-compound-i","display_name":"Prostaglandin H synthase compound I","entity_type_key":"protein_state"},"role":"reduced_intermediate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"22f2788f-df4b-5ff7-a89f-ace09650416a","slug":"active-site-tyrosyl-radical","display_name":"The cyclooxygenase active-site tyrosyl radical","entity_type_key":"protein_state"},"role":"quenched_state","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ca772a9c-94e9-5072-a283-e25995682a15","slug":"pghs-peroxidase-site","display_name":"The peroxidase site of prostaglandin H synthase","entity_type_key":"protein_state"},"role":"site_of_action","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"b4ad67ed-ff1f-5c41-a6a4-040205a3bdf3","slug":"indomethacin","display_name":"Indomethacin","entity_type_key":"small_molecule"},"role":"co_tested_drug","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"db2a1421-bdbf-5d98-9292-0b308f88cdfc","slug":"reducing-cosubstrate","display_name":"A reducing cosubstrate of the peroxidase","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"e43c3122-fa3d-5d7e-9714-9707230d414c","slug":"pghs-compound-ii","display_name":"Prostaglandin H synthase compound II","entity_type_key":"protein_state"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/paracetamol-research/1727638.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"028284c7b657c213a3052d362a0a5d050b1678d9ab3c5403b8e68d3631494c0c\", \"start_char\": 0, \"end_char\": 1789, \"text_sha256\": \"028284c7b657c213a3052d362a0a5d050b1678d9ab3c5403b8e68d3631494c0c\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Rapid scan spectrometry and transient state kinetics of prostaglandin H synthase compound II reduction","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Phenol and hydroquinone as reducing cosubstrates, with indomethacin","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Measures the reduction step directly with rate constants rather than inferring it from inhibition. 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It uses phenol and hydroquinone rather than paracetamol, which is recorded on the claim.\nexposure: Phenol and hydroquinone as reducing cosubstrates, with indomethacin\nevidence_span: {\"source_cache\": \"artifacts/paracetamol-research/1727638.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"028284c7b657c213a3052d362a0a5d050b1678d9ab3c5403b8e68d3631494c0c\", \"start_char\": 0, \"end_char\": 1789, \"text_sha256\": \"028284c7b657c213a3052d362a0a5d050b1678d9ab3c5403b8e68d3631494c0c\"}\n[apap-p1727638] Reduction of prostaglandin H synthase compound II by phenol and hydroquinone, and the effect of indomethacin. 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