{"id":"42b97dbb-9575-5255-aae8-e3339c02fb56","stable_key":"f8641d02-8413-5bd8-92e9-62ad49286e81:asa-resolvin-rates-are-low","predicate":"limits","statement":"Characterising the oxygenation of omega-3 fatty acids by aspirin-treated human cyclooxygenase-2 in vitro suggested that the 18R- and 17R-resolvins putatively involved in resolution of inflammation, reportedly formed via aspirin-acetylated cyclooxygenase-2 from eicosapentaenoic and docosahexaenoic acid, could be formed only at low rates corresponding to less than 1 and 5% respectively of the rates of formation of prostaglandin H2 by the native enzyme.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"705ae461-7c46-5b26-8ab1-39682c3c1228","mechanism_event_label":"Measured as rates rather than as presence, the celebrated resolution mediators come out at a fraction of a percent.","subject":{"id":"cda05399-1c07-5459-b8e2-0edcf5066e94","slug":"acetylated-cox2","display_name":"Aspirin-acetylated cyclooxygenase-2","entity_type_key":"protein_state"},"object":{"id":"76a548e7-1d27-5462-aec3-f29f5e67b427","slug":"17r-18r-resolvins","display_name":"17R and 18R resolvins","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"705ae461-7c46-5b26-8ab1-39682c3c1228","stable_key":"f8641d02-8413-5bd8-92e9-62ad49286e81:asa-resolvin-rates-are-low-event","event_type":"biochemical_relationship","label":"Measured as rates rather than as presence, the celebrated resolution mediators come out at a fraction of a percent.","description":"Characterising the oxygenation of omega-3 fatty acids by aspirin-treated human cyclooxygenase-2 in vitro suggested that the 18R- and 17R-resolvins putatively involved in resolution of inflammation, reportedly formed via aspirin-acetylated cyclooxygenase-2 from eicosapentaenoic and docosahexaenoic acid, could be formed only at low rates corresponding to less than 1 and 5% respectively of the rates of formation of prostaglandin H2 by the native enzyme.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6224759c-6cc3-5e8d-8749-95fcfc934d2a","slug":"aspirin-triggered-lipoxins","display_name":"Aspirin-triggered 15R-epimeric lipoxins","entity_type_key":"small_molecule"},"role":"related_class","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"cda05399-1c07-5459-b8e2-0edcf5066e94","slug":"acetylated-cox2","display_name":"Aspirin-acetylated cyclooxygenase-2","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"76a548e7-1d27-5462-aec3-f29f5e67b427","slug":"17r-18r-resolvins","display_name":"17R and 18R resolvins","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/aspirin-research/20194532.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"09427e18078449741ea9ea42dc91a16f50ca9f604ec05c4decbb255731104eaf\", \"start_char\": 0, \"end_char\": 1441, \"text_sha256\": \"09427e18078449741ea9ea42dc91a16f50ca9f604ec05c4decbb255731104eaf\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Quantitative characterisation of aspirin-acetylated human cyclooxygenase-2 monomers using diclofenac to distinguish them","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Aspirin acetylation with arachidonic, eicosapentaenoic and docosahexaenoic acid as substrates","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Measures rates rather than presence, and reaches a much less generous estimate of resolvin formation than the reports it tests. 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(2010). https://pubmed.ncbi.nlm.nih.gov/20194532/ DOI: 10.1124/mol.109.063115","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cyclooxygenase-2 homodimer","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b67690a5-ce19-5e28-a592-b8d43fa44f32","evidence_kind":"source_excerpt","locator":"Lines 338-349","start_line":338,"end_line":349,"excerpt":"### asa-resolvin-rates-are-low\nCharacterising the oxygenation of omega-3 fatty acids by aspirin-treated human cyclooxygenase-2 in vitro suggested that the 18R- and 17R-resolvins putatively involved in resolution of inflammation, reportedly formed via aspirin-acetylated cyclooxygenase-2 from eicosapentaenoic and docosahexaenoic acid, could be formed only at low rates corresponding to less than 1 and 5% respectively of the rates of formation of prostaglandin H2 by the native enzyme.\nCondition category: normal\nnutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes.\nplain_language: Measured as rates rather than as presence, the celebrated resolution mediators come out at a fraction of a percent.\norganism: Human enzyme\ntissue_or_cell_type: Cyclooxygenase-2 homodimer\nexperimental_model: Quantitative characterisation of aspirin-acetylated human cyclooxygenase-2 monomers using diclofenac to distinguish them\nlimitations: Measures rates rather than presence, and reaches a much less generous estimate of resolvin formation than the reports it tests. It is an in vitro enzyme study, so it does not exclude accumulation or amplification in a living tissue.\nexposure: Aspirin acetylation with arachidonic, eicosapentaenoic and docosahexaenoic acid as substrates\nevidence_span: {\"source_cache\": \"artifacts/aspirin-research/20194532.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"09427e18078449741ea9ea42dc91a16f50ca9f604ec05c4decbb255731104eaf\", \"start_char\": 0, \"end_char\": 1441, \"text_sha256\": \"09427e18078449741ea9ea42dc91a16f50ca9f604ec05c4decbb255731104eaf\"}\n[asa-p20194532] Asymmetric acetylation of the cyclooxygenase-2 homodimer by aspirin and its effects on the oxygenation of arachidonic, eicosapentaenoic, and docosahexaenoic acids. (2010). https://pubmed.ncbi.nlm.nih.gov/20194532/ DOI: 10.1124/mol.109.063115","model_system":"Quantitative characterisation of aspirin-acetylated human cyclooxygenase-2 monomers using diclofenac to distinguish them","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [asa-p20194532] Asymmetric acetylation of the cyclooxygenase-2 homodimer by aspirin and its effects on the oxygenation of arachidonic, eicosapentaenoic, and docosahexaenoic acids. (2010). https://pubmed.ncbi.nlm.nih.gov/20194532/ DOI: 10.1124/mol.109.063115","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"712cf519-cd27-5a8b-9e2f-961a98d7a27e","stable_key":"import-f8641d02-8413-5bd8-92e9-62ad49286e81","title":"Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22)","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":"93dd4343051c131e40d4fc3c95a978cd65478c13dcdb3f2d42507c49b09cb647","revision_id":"694e8ee7-49ca-5e6c-b58b-8ba8f82c2ad8","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"bde13e0b-a741-50bd-aff8-4ba97ed256de","title":"Do aspirin-triggered pro-resolving mediators form in amounts that matter?","kind":"contradiction","status":"open","why":"Coincubating human endothelial cells with neutrophils, aspirin and not indomethacin, salicylate or dexamethasone triggered a class of 15R-epimeric lipoxins, two of which inhibited leukotriene B4-mediated neutrophil adhesion with 15-epi-lipoxin A4 active in the nanomolar range. A later quantitative study of the same enzyme measured rates rather than presence and found that the analogous 18R- and 17R-resolvins could be formed only at less than 1% and 5% of the rate at which native enzyme makes prostaglandin H2, and that aspirin acetylates only one monomer of the homodimer, the untouched partner continuing at 15 to 20% of native rate. The two are not measuring the same thing: one asks whether a potent mediator is produced and acts, the other asks how fast. A mediator active at nanomolar concentrations does not need a high rate of formation, and an isolated enzyme preparation does not capture transcellular amplification. The disagreement about whether this route is quantitatively important is recorded, not resolved.","resolution":"Unresolved; needs review.","created_at":"2026-09-22 06:15:08","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/bde13e0b-a741-50bd-aff8-4ba97ed256de","sides":[{"conflict_id":"bde13e0b-a741-50bd-aff8-4ba97ed256de","ordinal":0,"label":"Aspirin, and not the other anti-inflammatories tested, makes the body build a mediator it otherwise never makes.","revision_id":"694e8ee7-49ca-5e6c-b58b-8ba8f82c2ad8","start_line":312,"end_line":323,"quote":"### asa-aspirin-triggers-lipoxins\nAspirin triggered transcellular biosynthesis of a previously unrecognised class of eicosanoids during coincubations of human umbilical vein endothelial cells and neutrophils, generated with aspirin but not by indomethacin, salicylate or dexamethasone, enhanced by interleukin-1-beta which induced cyclooxygenase-2 but not 15-lipoxygenase; four products proved to be 15R-epimers of lipoxins, two were potent inhibitors of leukotriene B4-mediated neutrophil adhesion to endothelium, with 15-epi-lipoxin A4 active in the nanomolar range, an example of a drug pirating endogenous biosynthetic mechanisms to trigger new mediators.\nCondition category: normal\nnutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes.\nplain_language: Aspirin, and not the other anti-inflammatories tested, makes the body build a mediator it otherwise never makes.\norganism: Human cells\ntissue_or_cell_type: Endothelium and neutrophils\nexperimental_model: Coincubations of human umbilical vein endothelial cells and neutrophils with physical characterisation of the products\nlimitations: The comparator set is what makes this strong: three other anti-inflammatory drugs including salicylate failed to produce the same products. It is a cell coincubation, and the nanomolar activity is measured on adhesion in vitro.\nexposure: Aspirin compared against indomethacin, salicylate and dexamethasone, with interleukin-1-beta induction and several costimuli\nevidence_span: {\"source_cache\": \"artifacts/aspirin-research/7568157.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"d9e7b80265068fb60f67e97c9d46de7a25e0099151b6d7fbc688f70a29ee9b9b\", \"start_char\": 0, \"end_char\": 2036, \"text_sha256\": \"d9e7b80265068fb60f67e97c9d46de7a25e0099151b6d7fbc688f70a29ee9b9b\"}\n[asa-p7568157] Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. (1995). https://pubmed.ncbi.nlm.nih.gov/7568157/ DOI: 10.1073/pnas.92.21.9475","source_key":"import-f8641d02-8413-5bd8-92e9-62ad49286e81","source_title":"Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22)","claim_ids":["903f64d9-0406-58f4-b4d7-4d37192fa16f"]},{"conflict_id":"bde13e0b-a741-50bd-aff8-4ba97ed256de","ordinal":1,"label":"Measured as rates rather than as presence, the celebrated resolution mediators come out at a fraction of a percent.","revision_id":"694e8ee7-49ca-5e6c-b58b-8ba8f82c2ad8","start_line":338,"end_line":349,"quote":"### asa-resolvin-rates-are-low\nCharacterising the oxygenation of omega-3 fatty acids by aspirin-treated human cyclooxygenase-2 in vitro suggested that the 18R- and 17R-resolvins putatively involved in resolution of inflammation, reportedly formed via aspirin-acetylated cyclooxygenase-2 from eicosapentaenoic and docosahexaenoic acid, could be formed only at low rates corresponding to less than 1 and 5% respectively of the rates of formation of prostaglandin H2 by the native enzyme.\nCondition category: normal\nnutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes.\nplain_language: Measured as rates rather than as presence, the celebrated resolution mediators come out at a fraction of a percent.\norganism: Human enzyme\ntissue_or_cell_type: Cyclooxygenase-2 homodimer\nexperimental_model: Quantitative characterisation of aspirin-acetylated human cyclooxygenase-2 monomers using diclofenac to distinguish them\nlimitations: Measures rates rather than presence, and reaches a much less generous estimate of resolvin formation than the reports it tests. It is an in vitro enzyme study, so it does not exclude accumulation or amplification in a living tissue.\nexposure: Aspirin acetylation with arachidonic, eicosapentaenoic and docosahexaenoic acid as substrates\nevidence_span: {\"source_cache\": \"artifacts/aspirin-research/20194532.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"09427e18078449741ea9ea42dc91a16f50ca9f604ec05c4decbb255731104eaf\", \"start_char\": 0, \"end_char\": 1441, \"text_sha256\": \"09427e18078449741ea9ea42dc91a16f50ca9f604ec05c4decbb255731104eaf\"}\n[asa-p20194532] Asymmetric acetylation of the cyclooxygenase-2 homodimer by aspirin and its effects on the oxygenation of arachidonic, eicosapentaenoic, and docosahexaenoic acids. (2010). https://pubmed.ncbi.nlm.nih.gov/20194532/ DOI: 10.1124/mol.109.063115","source_key":"import-f8641d02-8413-5bd8-92e9-62ad49286e81","source_title":"Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22)","claim_ids":["42b97dbb-9575-5255-aae8-e3339c02fb56"]}]}],"corrections":[],"research":null}