Aspirin-acetylated cyclooxygenase-2

evidence_span

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experimental_model

Crystal structures of an S530T murine COX-2 mutant, aspirin-acetylated human COX-2 and human COX-2 with salicylate, at 1.9 to 2.4 angstrom

exposure

Aspirin acetylation and salicylate binding, with an S530T/G533V double mutant and purification in several detergent systems

limitations

Much higher resolution than the 1995 structure and it captures salicylate separately. The authors note that detergent and lipid in the membrane-binding domain change the acetylation rate in vitro, which is a caution about all such measurements.

nutrient_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. · Aspirin / acetylsalicylic acid

organism

Mouse and human enzyme

plain_language

At high resolution the acetyl group seals the groove completely, and salicylate is caught sitting where aspirin sits before it reacts.

primary_references

[asa-p26859324] Crystal Structure of Aspirin-Acetylated Human Cyclooxygenase-2: Insight into the Formation of Products with Reversed Stereochemistry. (2016). https://pubmed.ncbi.nlm.nih.gov/26859324/ DOI: 10.1021/acs.biochem.5b01378

tissue_or_cell_type

Crystallised cyclooxygenase-2

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) · lines 156–167

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structures of an S530T murine COX-2 mutant, aspirin-acetylated human COX-2 and human COX-2 with salicylate, at 1.9 to 2.4 angstrom · source_derived_draft · unverified_draft

### asa-acetyl-blocks-the-groove The crystal structures reveal that the acetylated Ser-530 completely blocks access to the hydrophobic groove, that the observed binding pose of salicylate is reflective of the enzyme-inhibitor complex prior to acetylation, and that the observed Thr-530 rotamer in the S530T mutant does not impede access to the groove; differential acetylation of COX-2 purified in various detergent systems and nanodiscs indicates that detergent and lipid binding within the membrane-binding domain alters the rate of the acetylation reaction in vitro. Condition category: normal nutrient_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. plain_language: At high resolution the acetyl group seals the groove completely, and salicylate is caught sitting where aspirin sits before it reacts. organism: Mouse and human enzyme tissue_or_cell_type: Crystallised cyclooxygenase-2 experimental_model: Crystal structures of an S530T murine COX-2 mutant, aspirin-acetylated human COX-2 and human COX-2 with salicylate, at 1.9 to 2.4 angstrom limitations: Much higher resolution than the 1995 structure and it captures salicylate separately. The authors note that detergent and lipid in the membrane-binding domain change the acetylation rate in vitro, which is a caution about all such measurements. exposure: Aspirin acetylation and salicylate binding, with an S530T/G533V double mutant and purification in several detergent systems evidence_span: {"source_cache": "artifacts/aspirin-research/26859324.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2d5dab1d6b7576a909c9cef6b5c247e6a399946afbf7ef6d428d67475a363c34", "start_char": 0, "end_char": 1553, "text_sha256": "2d5dab1d6b7576a909c9cef6b5c247e6a399946afbf7ef6d428d67475a363c34"} [asa-p26859324] Crystal Structure of Aspirin-Acetylated Human Cyclooxygenase-2: Insight into the Formation of Products with Reversed Stereochemistry. (2016). https://pubmed.ncbi.nlm.nih.gov/26859324/ DOI: 10.1021/acs.biochem.5b01378

evidence_span

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experimental_model

Human cyclooxygenase-1 and -2 expressed in cos-1 cells treated with aspirin and with carbon-14 labelled aspirin, with a mutant series at Ser-516

exposure

Aspirin acetylation, with S516A, S516N, S516Q and S516M substitutions

limitations

Identifies the site by direct labelling and explains the isoform difference by active site volume. Recombinant enzyme in a heterologous cell line.

nutrient_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. · Aspirin / acetylsalicylic acid

organism

Human enzyme

plain_language

Acetylating the second enzyme does not switch it off; it turns it into a machine that makes something else.

primary_references

[asa-p8175750] Acetylation of human prostaglandin endoperoxide synthase-2 (cyclooxygenase-2) by aspirin. (1994). https://pubmed.ncbi.nlm.nih.gov/8175750/ DOI: 10.1016/s0021-9258(17)36820-5

tissue_or_cell_type

Recombinant cyclooxygenase

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) · lines 208–219

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cyclooxygenase-1 and -2 expressed in cos-1 cells treated with aspirin and with carbon-14 labelled aspirin, with a mutant series at Ser-516 · source_derived_draft · unverified_draft

### asa-cox2-becomes-a-lipoxygenase Aspirin treatment of human cyclooxygenase-1 caused time-dependent inactivation of oxygenase activity, whereas aspirin treatment of cyclooxygenase-2 produced an enzyme which retained oxygenase activity but formed exclusively 15-hydroxyeicosatetraenoic acid instead of prostaglandin H2, exclusively of the 15R configuration, with Km values for arachidonate of native and aspirin-treated cyclooxygenase-2 about the same, suggesting arachidonate binds to both in a similar manner. Condition category: normal nutrient_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. plain_language: Acetylating the second enzyme does not switch it off; it turns it into a machine that makes something else. organism: Human enzyme tissue_or_cell_type: Recombinant cyclooxygenase experimental_model: Human cyclooxygenase-1 and -2 expressed in cos-1 cells treated with aspirin and with carbon-14 labelled aspirin, with a mutant series at Ser-516 limitations: Identifies the site by direct labelling and explains the isoform difference by active site volume. Recombinant enzyme in a heterologous cell line. exposure: Aspirin acetylation, with S516A, S516N, S516Q and S516M substitutions evidence_span: {"source_cache": "artifacts/aspirin-research/8175750.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9ba85af90c62b157cf53032375ca703e8b78eff6ddd22ad627bbd7e65965d8e9", "start_char": 0, "end_char": 1786, "text_sha256": "9ba85af90c62b157cf53032375ca703e8b78eff6ddd22ad627bbd7e65965d8e9"} [asa-p8175750] Acetylation of human prostaglandin endoperoxide synthase-2 (cyclooxygenase-2) by aspirin. (1994). https://pubmed.ncbi.nlm.nih.gov/8175750/ DOI: 10.1016/s0021-9258(17)36820-5

evidence_span

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experimental_model

Radiolabelled substrate and LC-MS analysis of aspirin-acetylated COX-2 products, with human leukocytes and platelet aggregation assays

exposure

Aspirin acetylation, with lipopolysaccharide-induced cyclooxygenase-2 in leukocytes and a thromboxane receptor agonist on platelets

limitations

Shows the acetylated enzyme keeps more of its original chemistry than the HETE story implies, and links the product to a measured platelet effect. Isolated cells rather than treated people.

nutrient_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. · Aspirin / acetylsalicylic acid

organism

Human

plain_language

The rerouted enzyme has not stopped making prostaglandins; it makes mirror-image ones, more slowly.

primary_references

[asa-p30096040] Residual cyclooxygenase activity of aspirin-acetylated COX-2 forms 15 R-prostaglandins that inhibit platelet aggregation. (2019). https://pubmed.ncbi.nlm.nih.gov/30096040/ DOI: 10.1096/fj.201801018r

tissue_or_cell_type

Recombinant enzyme and isolated leukocytes and platelets

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) · lines 286–297

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabelled substrate and LC-MS analysis of aspirin-acetylated COX-2 products, with human leukocytes and platelet aggregation assays · source_derived_draft · unverified_draft

### asa-it-still-makes-prostaglandins Acetylated cyclooxygenase-2 also retains cyclooxygenase activity forming predominantly 15R-configuration prostaglandins, 70% or 62% 15R by radiolabelled substrate or LC-MS respectively, and although the Km of arachidonic acid for the acetylated enzyme was about threefold lower than for uninhibited enzyme the catalytic efficiency for prostaglandin formation was reduced tenfold through a decrease in Vmax. Condition category: normal nutrient_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. plain_language: The rerouted enzyme has not stopped making prostaglandins; it makes mirror-image ones, more slowly. organism: Human tissue_or_cell_type: Recombinant enzyme and isolated leukocytes and platelets experimental_model: Radiolabelled substrate and LC-MS analysis of aspirin-acetylated COX-2 products, with human leukocytes and platelet aggregation assays limitations: Shows the acetylated enzyme keeps more of its original chemistry than the HETE story implies, and links the product to a measured platelet effect. Isolated cells rather than treated people. exposure: Aspirin acetylation, with lipopolysaccharide-induced cyclooxygenase-2 in leukocytes and a thromboxane receptor agonist on platelets evidence_span: {"source_cache": "artifacts/aspirin-research/30096040.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2bd9c817ec4fe31752028634955f604eb00829efc93a72d5fc7e22be7f5739b8", "start_char": 0, "end_char": 1666, "text_sha256": "2bd9c817ec4fe31752028634955f604eb00829efc93a72d5fc7e22be7f5739b8"} [asa-p30096040] Residual cyclooxygenase activity of aspirin-acetylated COX-2 forms 15 R-prostaglandins that inhibit platelet aggregation. (2019). https://pubmed.ncbi.nlm.nih.gov/30096040/ DOI: 10.1096/fj.201801018r

evidence_span

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experimental_model

Quantitative characterisation of aspirin-acetylated human cyclooxygenase-2 monomers using diclofenac to distinguish them

exposure

Aspirin acetylation with arachidonic, eicosapentaenoic and docosahexaenoic acid as substrates

limitations

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.

nutrient_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. · Aspirin / acetylsalicylic acid

organism

Human enzyme

plain_language

Measured as rates rather than as presence, the celebrated resolution mediators come out at a fraction of a percent.

primary_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

tissue_or_cell_type

Cyclooxygenase-2 homodimer

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) · lines 338–349

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantitative characterisation of aspirin-acetylated human cyclooxygenase-2 monomers using diclofenac to distinguish them · source_derived_draft · unverified_draft

### asa-resolvin-rates-are-low 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. Condition category: normal nutrient_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. plain_language: Measured as rates rather than as presence, the celebrated resolution mediators come out at a fraction of a percent. organism: Human enzyme tissue_or_cell_type: Cyclooxygenase-2 homodimer experimental_model: Quantitative characterisation of aspirin-acetylated human cyclooxygenase-2 monomers using diclofenac to distinguish them limitations: 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. exposure: Aspirin acetylation with arachidonic, eicosapentaenoic and docosahexaenoic acid as substrates evidence_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"} [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

evidence_span

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experimental_model

Kinetic characterisation of aspirin-acetylated cyclooxygenase-2 and the S516M mutant against a panel of non-steroidal anti-inflammatory drugs

exposure

Aspirin acetylation and the methionine mutant, tested with indomethacin, diclofenac, meclofenamic acid and selective inhibitors

limitations

Quantifies how efficient the new activity is, which most descriptions of the switch do not. Purified and recombinant enzyme rather than intact cells.

nutrient_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. · Aspirin / acetylsalicylic acid

organism

Enzyme

plain_language

The rerouted enzyme works well enough that arachidonate does not pile up and spill into other pathways.

primary_references

[asa-p9016346] Altered sensitivity of aspirin-acetylated prostaglandin G/H synthase-2 to inhibition by nonsteroidal anti-inflammatory drugs. (1997). https://pubmed.ncbi.nlm.nih.gov/9016346/ DOI: 10.1124/mol.51.1.52

tissue_or_cell_type

Cyclooxygenase-2

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) · lines 260–271

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Kinetic characterisation of aspirin-acetylated cyclooxygenase-2 and the S516M mutant against a panel of non-steroidal anti-inflammatory drugs · source_derived_draft · unverified_draft

### asa-the-new-activity-is-efficient Both the S516M mutant and the aspirin-acetylated form of cyclooxygenase-2 synthesise 15(R)-HETE with apparent Km values for arachidonic acid within tenfold of untreated enzyme and with similar time courses of turnover-dependent inactivation, and the conversion of arachidonic acid to 15-HETE by acetylated cyclooxygenase-2 is an efficient process providing a unique mechanism among non-steroidal anti-inflammatory drugs that will not lead to arachidonic acid accumulation or shunting to other biosynthetic pathways. Condition category: normal nutrient_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. plain_language: The rerouted enzyme works well enough that arachidonate does not pile up and spill into other pathways. organism: Enzyme tissue_or_cell_type: Cyclooxygenase-2 experimental_model: Kinetic characterisation of aspirin-acetylated cyclooxygenase-2 and the S516M mutant against a panel of non-steroidal anti-inflammatory drugs limitations: Quantifies how efficient the new activity is, which most descriptions of the switch do not. Purified and recombinant enzyme rather than intact cells. exposure: Aspirin acetylation and the methionine mutant, tested with indomethacin, diclofenac, meclofenamic acid and selective inhibitors evidence_span: {"source_cache": "artifacts/aspirin-research/9016346.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2cc2efefceabbee7bb4f1052db8fc86ee218409fe56981cf92b707c7b0ef531b", "start_char": 0, "end_char": 1899, "text_sha256": "2cc2efefceabbee7bb4f1052db8fc86ee218409fe56981cf92b707c7b0ef531b"} [asa-p9016346] Altered sensitivity of aspirin-acetylated prostaglandin G/H synthase-2 to inhibition by nonsteroidal anti-inflammatory drugs. (1997). https://pubmed.ncbi.nlm.nih.gov/9016346/ DOI: 10.1124/mol.51.1.52

evidence_span

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experimental_model

Radiolabelled substrate and LC-MS analysis of aspirin-acetylated COX-2 products, with human leukocytes and platelet aggregation assays

exposure

Aspirin acetylation, with lipopolysaccharide-induced cyclooxygenase-2 in leukocytes and a thromboxane receptor agonist on platelets

limitations

Shows the acetylated enzyme keeps more of its original chemistry than the HETE story implies, and links the product to a measured platelet effect. Isolated cells rather than treated people.

nutrient_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. · Aspirin / acetylsalicylic acid

organism

Human

plain_language

One of those mirror-image products is itself an antiplatelet agent, working through a different receptor.

primary_references

[asa-p30096040] Residual cyclooxygenase activity of aspirin-acetylated COX-2 forms 15 R-prostaglandins that inhibit platelet aggregation. (2019). https://pubmed.ncbi.nlm.nih.gov/30096040/ DOI: 10.1096/fj.201801018r

tissue_or_cell_type

Recombinant enzyme and isolated leukocytes and platelets

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) · lines 299–310

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabelled substrate and LC-MS analysis of aspirin-acetylated COX-2 products, with human leukocytes and platelet aggregation assays · source_derived_draft · unverified_draft

### asa-15r-pgd2-blocks-platelets Aspirin increased 15R-prostaglandin D2 but not 15R-prostaglandin E2 in isolated human leukocytes activated with lipopolysaccharide to induce cyclooxygenase-2, and 15R-prostaglandin D2 inhibited human platelet aggregation induced by the thromboxane receptor agonist U46,619, an effect abrogated by an antagonist of the DP1 prostanoid receptor, so 15R-prostaglandins are novel products of aspirin therapy that may contribute to its antiplatelet and other effects. Condition category: normal nutrient_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. plain_language: One of those mirror-image products is itself an antiplatelet agent, working through a different receptor. organism: Human tissue_or_cell_type: Recombinant enzyme and isolated leukocytes and platelets experimental_model: Radiolabelled substrate and LC-MS analysis of aspirin-acetylated COX-2 products, with human leukocytes and platelet aggregation assays limitations: Shows the acetylated enzyme keeps more of its original chemistry than the HETE story implies, and links the product to a measured platelet effect. Isolated cells rather than treated people. exposure: Aspirin acetylation, with lipopolysaccharide-induced cyclooxygenase-2 in leukocytes and a thromboxane receptor agonist on platelets evidence_span: {"source_cache": "artifacts/aspirin-research/30096040.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2bd9c817ec4fe31752028634955f604eb00829efc93a72d5fc7e22be7f5739b8", "start_char": 0, "end_char": 1666, "text_sha256": "2bd9c817ec4fe31752028634955f604eb00829efc93a72d5fc7e22be7f5739b8"} [asa-p30096040] Residual cyclooxygenase activity of aspirin-acetylated COX-2 forms 15 R-prostaglandins that inhibit platelet aggregation. (2019). https://pubmed.ncbi.nlm.nih.gov/30096040/ DOI: 10.1096/fj.201801018r

evidence_span

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experimental_model

Coincubations of human umbilical vein endothelial cells and neutrophils with physical characterisation of the products

exposure

Aspirin compared against indomethacin, salicylate and dexamethasone, with interleukin-1-beta induction and several costimuli

limitations

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.

nutrient_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. · Aspirin / acetylsalicylic acid

organism

Human cells

plain_language

Aspirin, and not the other anti-inflammatories tested, makes the body build a mediator it otherwise never makes.

primary_references

[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

tissue_or_cell_type

Endothelium and neutrophils

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) · lines 312–323

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Coincubations of human umbilical vein endothelial cells and neutrophils with physical characterisation of the products · source_derived_draft · unverified_draft

### asa-aspirin-triggers-lipoxins Aspirin 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. Condition category: normal nutrient_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. plain_language: Aspirin, and not the other anti-inflammatories tested, makes the body build a mediator it otherwise never makes. organism: Human cells tissue_or_cell_type: Endothelium and neutrophils experimental_model: Coincubations of human umbilical vein endothelial cells and neutrophils with physical characterisation of the products limitations: 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. exposure: Aspirin compared against indomethacin, salicylate and dexamethasone, with interleukin-1-beta induction and several costimuli evidence_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"} [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

evidence_span

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experimental_model

Mutants of the putative acetylation site of human cyclooxygenase-2 expressed in COS-7 cells by recombinant vaccinia virus

exposure

Substitution at Ser516, including methionine, compared with aspirin preincubation

limitations

A second, independent identification of the same residue with a substitution that mimics the acetylated state. Vaccinia-driven expression in a heterologous line.

nutrient_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. · Aspirin / acetylsalicylic acid

organism

Human enzyme

plain_language

Putting a methionine where the acetyl group would go reproduces the switch without any drug.

primary_references

[asa-p8143845] Mutation of serine-516 in human prostaglandin G/H synthase-2 to methionine or aspirin acetylation of this residue stimulates 15-R-HETE synthesis. (1994). https://pubmed.ncbi.nlm.nih.gov/8143845/ DOI: 10.1016/0014-5793(94)80579-2

tissue_or_cell_type

Recombinant cyclooxygenase-2

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) · lines 234–245

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mutants of the putative acetylation site of human cyclooxygenase-2 expressed in COS-7 cells by recombinant vaccinia virus · source_derived_draft · unverified_draft

### asa-methionine-mimics-acetyl While prostaglandin synthesis by both isoforms is inhibited by aspirin, 15-R-hydroxyeicosatetraenoic acid synthesis by cyclooxygenase-2 but not cyclooxygenase-1 is stimulated by preincubation with aspirin, and enzyme activity and inhibitor sensitivity studies of mutants provide evidence that Ser516 is the aspirin acetylation site of human cyclooxygenase-2 and that substitution of a methionine at this position can mimic the effects of aspirin acetylation on enzyme activity. Condition category: normal nutrient_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. plain_language: Putting a methionine where the acetyl group would go reproduces the switch without any drug. organism: Human enzyme tissue_or_cell_type: Recombinant cyclooxygenase-2 experimental_model: Mutants of the putative acetylation site of human cyclooxygenase-2 expressed in COS-7 cells by recombinant vaccinia virus limitations: A second, independent identification of the same residue with a substitution that mimics the acetylated state. Vaccinia-driven expression in a heterologous line. exposure: Substitution at Ser516, including methionine, compared with aspirin preincubation evidence_span: {"source_cache": "artifacts/aspirin-research/8143845.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ddf63e3296e1f35a88de948bc23fda6654c2eaf247b1d6d3987e95989c966f93", "start_char": 0, "end_char": 903, "text_sha256": "ddf63e3296e1f35a88de948bc23fda6654c2eaf247b1d6d3987e95989c966f93"} [asa-p8143845] Mutation of serine-516 in human prostaglandin G/H synthase-2 to methionine or aspirin acetylation of this residue stimulates 15-R-HETE synthesis. (1994). https://pubmed.ncbi.nlm.nih.gov/8143845/ DOI: 10.1016/0014-5793(94)80579-2

evidence_span

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experimental_model

Quantitative characterisation of aspirin-acetylated human cyclooxygenase-2 monomers using diclofenac to distinguish them

exposure

Aspirin acetylation with arachidonic, eicosapentaenoic and docosahexaenoic acid as substrates

limitations

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.

nutrient_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. · Aspirin / acetylsalicylic acid

organism

Human enzyme

plain_language

Aspirin only ever modifies half of the paired enzyme, and the untouched half carries on at a fifth speed.

primary_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

tissue_or_cell_type

Cyclooxygenase-2 homodimer

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) · lines 325–336

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantitative characterisation of aspirin-acetylated human cyclooxygenase-2 monomers using diclofenac to distinguish them · source_derived_draft · unverified_draft

### asa-only-one-monomer-is-acetylated Aspirin maximally acetylates one monomer of human cyclooxygenase-2, the acetylated monomer forming 15-hydroperoxyeicosatetraenoic acid from arachidonic acid while the nonacetylated partner monomer forms mainly prostaglandin H2 but at only 15 to 20% of the rate of native enzyme, conclusions based on diclofenac binding a single monomer of native enzyme having an unmodified Ser530 and on diclofenac inhibiting prostaglandin H2 but not 15-hydroperoxyeicosatetraenoic acid formation by the acetylated enzyme. Condition category: normal nutrient_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. plain_language: Aspirin only ever modifies half of the paired enzyme, and the untouched half carries on at a fifth speed. organism: Human enzyme tissue_or_cell_type: Cyclooxygenase-2 homodimer experimental_model: Quantitative characterisation of aspirin-acetylated human cyclooxygenase-2 monomers using diclofenac to distinguish them limitations: 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. exposure: Aspirin acetylation with arachidonic, eicosapentaenoic and docosahexaenoic acid as substrates evidence_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"} [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

evidence_span

{"source_cache": "artifacts/aspirin-research/23786234.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bdf3d33c4cc14fc4b2190180d78b68971144966047e654abb59b9ca7a83ab824", "start_char": 0, "end_char": 834, "text_sha256": "bdf3d33c4cc14fc4b2190180d78b68971144966047e654abb59b9ca7a83ab824"}

experimental_model

Computational modelling of oxygenation stereospecificity in native and aspirin-acetylated cyclooxygenase-2

exposure

A mechanistic hypothesis tested against experimental oxygenation patterns

limitations

A computational model reproducing known patterns, not a new measurement. It offers an explanation for the switch rather than evidence that it occurs.

nutrient_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. · Aspirin / acetylsalicylic acid

organism

Enzyme

plain_language

The same bulk that blocks the first enzyme explains why the second one makes mirror-image products.

primary_references

[asa-p23786234] A mechanistic hypothesis for the aspirin-induced switch in lipid mediator production by cyclooxygenase-2. (2013). https://pubmed.ncbi.nlm.nih.gov/23786234/ DOI: 10.1021/ja402870k

tissue_or_cell_type

Cyclooxygenase-2

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) · lines 351–362

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Computational modelling of oxygenation stereospecificity in native and aspirin-acetylated cyclooxygenase-2 · source_derived_draft · unverified_draft

### asa-steric-shielding-explains-stereochemistry A mechanistic hypothesis identifying steric shielding as the main determinant of oxygenation stereospecificity in cyclooxygenase-2 is supported by a computational model which accurately reproduces experimental oxygenation patterns on both native and aspirin-inhibited enzyme, addressing why Ser530 acetylation shifts the stereochemistry and relative abundance of generated products. Condition category: normal nutrient_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. plain_language: The same bulk that blocks the first enzyme explains why the second one makes mirror-image products. organism: Enzyme tissue_or_cell_type: Cyclooxygenase-2 experimental_model: Computational modelling of oxygenation stereospecificity in native and aspirin-acetylated cyclooxygenase-2 limitations: A computational model reproducing known patterns, not a new measurement. It offers an explanation for the switch rather than evidence that it occurs. exposure: A mechanistic hypothesis tested against experimental oxygenation patterns evidence_span: {"source_cache": "artifacts/aspirin-research/23786234.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bdf3d33c4cc14fc4b2190180d78b68971144966047e654abb59b9ca7a83ab824", "start_char": 0, "end_char": 834, "text_sha256": "bdf3d33c4cc14fc4b2190180d78b68971144966047e654abb59b9ca7a83ab824"} [asa-p23786234] A mechanistic hypothesis for the aspirin-induced switch in lipid mediator production by cyclooxygenase-2. (2013). https://pubmed.ncbi.nlm.nih.gov/23786234/ DOI: 10.1021/ja402870k