Component

Cyclooxygenase-2 with methionine substituted at position 516

Cyclooxygenase-2 with methionine substituted at position 516. Species, exposure and limitations are retained in each linked claim.

2 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. 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.

    Cyclooxygenase-2 with methionine substituted at position 516 → 15(R)-hydroxyeicosatetraenoic acid source_derived_draftungraded
    Experimental context and source evidence
    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"}
    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
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. 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.

    Aspirin-acetylated cyclooxygenase-2 → 15(R)-hydroxyeicosatetraenoic acid source_derived_draftungraded
    Experimental context and source evidence
    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"}
    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
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards