Component

The cyclooxygenase activity of prostaglandin endoperoxide synthase

The cyclooxygenase activity of prostaglandin endoperoxide synthase. Species, exposure and limitations are retained in each linked claim.

4 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 acts on it

  1. The Ala530 mutant of prostaglandin endoperoxide synthase had both cyclooxygenase and hydroperoxidase activity while the Asn530 mutant lacked cyclooxygenase activity but retained hydroperoxidase activity, establishing that the hydroxyl group of Ser530 is not essential for catalysis or substrate binding and suggesting that a bulky group at position 530, such as that introduced by aspirin acetylation, prevents arachidonate binding to the cyclooxygenase active site.

    Cyclooxygenase-1 with asparagine substituted at position 530 → The cyclooxygenase activity of prostaglandin endoperoxide synthase source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/aspirin-research/2144687.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0a66f17b41129423ecb73bf520dad47b666792a6477552db04272474fc79be24", "start_char": 0, "end_char": 1595, "text_sha256": "0a66f17b41129423ecb73bf520dad47b666792a6477552db04272474fc79be24"}
    experimental_model
    Sequence comparison and site-directed mutagenesis across sheep, mouse and human prostaglandin endoperoxide synthase
    exposure
    Ser530 replaced with alanine and with asparagine, and tetranitromethane modification with ibuprofen protection
    limitations
    Extends the single mutant to a pair that differ in bulk. Sequence-based assignment of the heme ligands is inference from similarity, not structure.
    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
    Sheep, mouse and human enzyme
    plain_language
    Swap in a small residue and the enzyme is fine; swap in a bigger one and the cyclooxygenase half stops.
    primary_references
    [asa-p2144687] Structure-function relationships in sheep, mouse, and human prostaglandin endoperoxide G/H synthases. (1990). https://pubmed.ncbi.nlm.nih.gov/2144687/
    tissue_or_cell_type
    Recombinant enzyme

    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 104–115

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sequence comparison and site-directed mutagenesis across sheep, mouse and human prostaglandin endoperoxide synthase · source_derived_draft · unverified_draft

    ### asa-bulk-not-identity The Ala530 mutant of prostaglandin endoperoxide synthase had both cyclooxygenase and hydroperoxidase activity while the Asn530 mutant lacked cyclooxygenase activity but retained hydroperoxidase activity, establishing that the hydroxyl group of Ser530 is not essential for catalysis or substrate binding and suggesting that a bulky group at position 530, such as that introduced by aspirin acetylation, prevents arachidonate binding to the cyclooxygenase active site. 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: Swap in a small residue and the enzyme is fine; swap in a bigger one and the cyclooxygenase half stops. organism: Sheep, mouse and human enzyme tissue_or_cell_type: Recombinant enzyme experimental_model: Sequence comparison and site-directed mutagenesis across sheep, mouse and human prostaglandin endoperoxide synthase limitations: Extends the single mutant to a pair that differ in bulk. Sequence-based assignment of the heme ligands is inference from similarity, not structure. exposure: Ser530 replaced with alanine and with asparagine, and tetranitromethane modification with ibuprofen protection evidence_span: {"source_cache": "artifacts/aspirin-research/2144687.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0a66f17b41129423ecb73bf520dad47b666792a6477552db04272474fc79be24", "start_char": 0, "end_char": 1595, "text_sha256": "0a66f17b41129423ecb73bf520dad47b666792a6477552db04272474fc79be24"} [asa-p2144687] Structure-function relationships in sheep, mouse, and human prostaglandin endoperoxide G/H synthases. (1990). https://pubmed.ncbi.nlm.nih.gov/2144687/
    Complete structured claim and evidence

  2. Following ingestion of 650 milligrams of acetylsalicylate as compressed tablets, platelet cyclooxygenase activity was inhibited 95% within 45 minutes, enzyme activity was observed to increase within 8 hours and reached 10% of control level by 24 hours, a pattern suggesting that only circulating platelets are affected by ingestion; enteric-coated tablets gave comparable inhibition with a delayed onset reflecting delayed appearance of acetylsalicylate in plasma, and returned to control along a similar pattern.

    Aspirin / acetylsalicylic acid → The cyclooxygenase activity of prostaglandin endoperoxide synthase source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/aspirin-research/7355437.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "01e0a159576fdabca8185271b0d6acd2e790cff32c06ba1e68906afb3a63544a", "start_char": 0, "end_char": 909, "text_sha256": "01e0a159576fdabca8185271b0d6acd2e790cff32c06ba1e68906afb3a63544a"}
    experimental_model
    High pressure liquid chromatography of plasma acetylsalicylate and salicylate with radiometric platelet cyclooxygenase assay
    exposure
    650 milligrams of aspirin as compressed or enteric-coated tablets
    limitations
    Measures the parent drug and the metabolite separately alongside the enzyme effect, which is exactly the distinction this chapter turns on. Healthy subjects and a single dose.
    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 drug catches the platelets that are in the blood at the time, and nothing else.
    primary_references
    [asa-p7355437] Plasma acetylsalicylate and salicylate and platelet cyclooxygenase activity following plain and enteric-coated aspirin. (1980). https://pubmed.ncbi.nlm.nih.gov/7355437/ DOI: 10.1161/01.str.11.1.9
    tissue_or_cell_type
    Plasma 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 403–414

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · High pressure liquid chromatography of plasma acetylsalicylate and salicylate with radiometric platelet cyclooxygenase assay · source_derived_draft · unverified_draft

    ### asa-only-circulating-platelets Following ingestion of 650 milligrams of acetylsalicylate as compressed tablets, platelet cyclooxygenase activity was inhibited 95% within 45 minutes, enzyme activity was observed to increase within 8 hours and reached 10% of control level by 24 hours, a pattern suggesting that only circulating platelets are affected by ingestion; enteric-coated tablets gave comparable inhibition with a delayed onset reflecting delayed appearance of acetylsalicylate in plasma, and returned to control along a similar pattern. 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 drug catches the platelets that are in the blood at the time, and nothing else. organism: Human tissue_or_cell_type: Plasma and platelets experimental_model: High pressure liquid chromatography of plasma acetylsalicylate and salicylate with radiometric platelet cyclooxygenase assay limitations: Measures the parent drug and the metabolite separately alongside the enzyme effect, which is exactly the distinction this chapter turns on. Healthy subjects and a single dose. exposure: 650 milligrams of aspirin as compressed or enteric-coated tablets evidence_span: {"source_cache": "artifacts/aspirin-research/7355437.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "01e0a159576fdabca8185271b0d6acd2e790cff32c06ba1e68906afb3a63544a", "start_char": 0, "end_char": 909, "text_sha256": "01e0a159576fdabca8185271b0d6acd2e790cff32c06ba1e68906afb3a63544a"} [asa-p7355437] Plasma acetylsalicylate and salicylate and platelet cyclooxygenase activity following plain and enteric-coated aspirin. (1980). https://pubmed.ncbi.nlm.nih.gov/7355437/ DOI: 10.1161/01.str.11.1.9
    Complete structured claim and evidence

  3. Cos-1 cells transfected with native or Ser-530-to-alanine mutant sheep prostaglandin endoperoxide synthase expressed comparable cyclooxygenase and hydroperoxidase activities, with the same Km for arachidonate of 8 micromolar and the same ID50 values for reversible inhibition by flurbiprofen at 5 micromolar, flufenamate at 20 micromolar and aspirin at 20 millimolar; however only the native enzyme was irreversibly inactivated by aspirin, so the active site Ser-530 is not essential for catalysis or substrate binding.

    Cyclooxygenase-1 with alanine substituted at position 530 → The cyclooxygenase activity of prostaglandin endoperoxide synthase source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/aspirin-research/2108169.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c7b11508521a3854b432f3836de6e92ba9863c8edb244d747bb1c37634c0bb50", "start_char": 0, "end_char": 2076, "text_sha256": "c7b11508521a3854b432f3836de6e92ba9863c8edb244d747bb1c37634c0bb50"}
    experimental_model
    Site-directed mutagenesis of sheep prostaglandin endoperoxide synthase expressed in Cos-1 cells
    exposure
    Serine 530 replaced with alanine, compared with the native enzyme against aspirin and reversible inhibitors
    limitations
    The decisive experiment for the mechanism: it separates what the serine does for catalysis from what acetylating it does. Recombinant sheep enzyme, not human enzyme in a 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
    Sheep and mouse enzyme
    plain_language
    Remove the serine and the enzyme still works; it is there to be acetylated, not to do the chemistry.
    primary_references
    [asa-p2108169] The aspirin and heme-binding sites of ovine and murine prostaglandin endoperoxide synthases. (1990). https://pubmed.ncbi.nlm.nih.gov/2108169/ DOI: 10.1016/s0021-9258(19)34105-5
    tissue_or_cell_type
    Recombinant enzyme in Cos-1 cells

    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 78–89

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutagenesis of sheep prostaglandin endoperoxide synthase expressed in Cos-1 cells · source_derived_draft · unverified_draft

    ### asa-serine-is-not-catalytic Cos-1 cells transfected with native or Ser-530-to-alanine mutant sheep prostaglandin endoperoxide synthase expressed comparable cyclooxygenase and hydroperoxidase activities, with the same Km for arachidonate of 8 micromolar and the same ID50 values for reversible inhibition by flurbiprofen at 5 micromolar, flufenamate at 20 micromolar and aspirin at 20 millimolar; however only the native enzyme was irreversibly inactivated by aspirin, so the active site Ser-530 is not essential for catalysis or substrate binding. 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: Remove the serine and the enzyme still works; it is there to be acetylated, not to do the chemistry. organism: Sheep and mouse enzyme tissue_or_cell_type: Recombinant enzyme in Cos-1 cells experimental_model: Site-directed mutagenesis of sheep prostaglandin endoperoxide synthase expressed in Cos-1 cells limitations: The decisive experiment for the mechanism: it separates what the serine does for catalysis from what acetylating it does. Recombinant sheep enzyme, not human enzyme in a tissue. exposure: Serine 530 replaced with alanine, compared with the native enzyme against aspirin and reversible inhibitors evidence_span: {"source_cache": "artifacts/aspirin-research/2108169.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c7b11508521a3854b432f3836de6e92ba9863c8edb244d747bb1c37634c0bb50", "start_char": 0, "end_char": 2076, "text_sha256": "c7b11508521a3854b432f3836de6e92ba9863c8edb244d747bb1c37634c0bb50"} [asa-p2108169] The aspirin and heme-binding sites of ovine and murine prostaglandin endoperoxide synthases. (1990). https://pubmed.ncbi.nlm.nih.gov/2108169/ DOI: 10.1016/s0021-9258(19)34105-5
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Using site-directed mutagenesis to prepare five further substitutions of Ser-530, the presence of amino acids with bulky side chains at position 530 inhibited cyclooxygenase activity and decreased the apparent affinity of the enzyme for arachidonate, consistent with the proposal that aspirin inhibits by placing a larger than normal side chain at position 530; residues 529 to 533 all proved important for the peroxidase as well as the cyclooxygenase activity, and Phe-529 in particular was critical for structure and catalysis.

    Serine 530 of cyclooxygenase-1 → Binding of arachidonate in the cyclooxygenase active site source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/aspirin-research/1601897.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "616cbc367eb38194b858872cbf91108baa3b1dec7aa039a40f69a29fa7157c2d", "start_char": 0, "end_char": 1744, "text_sha256": "616cbc367eb38194b858872cbf91108baa3b1dec7aa039a40f69a29fa7157c2d"}
    experimental_model
    Five further substitutions at Ser-530 and substitutions at adjoining residues, expressed transiently in cos-1 cells
    exposure
    A graded series of side chains at position 530, plus substitutions at Phe-529, Leu-531, Lys-532 and Gly-533
    limitations
    Tests the steric hypothesis by varying the bulk systematically rather than with one mutant. Transient expression 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
    Enzyme
    plain_language
    The bigger the group put at that position, the worse the enzyme binds its substrate.
    primary_references
    [asa-p1601897] Prostaglandin endoperoxide synthase. The aspirin acetylation region. (1992). https://pubmed.ncbi.nlm.nih.gov/1601897/ DOI: 10.1016/s0021-9258(19)49852-9
    tissue_or_cell_type
    Recombinant prostaglandin endoperoxide H synthase-1

    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 117–128

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five further substitutions at Ser-530 and substitutions at adjoining residues, expressed transiently in cos-1 cells · source_derived_draft · unverified_draft

    ### asa-graded-bulk-series Using site-directed mutagenesis to prepare five further substitutions of Ser-530, the presence of amino acids with bulky side chains at position 530 inhibited cyclooxygenase activity and decreased the apparent affinity of the enzyme for arachidonate, consistent with the proposal that aspirin inhibits by placing a larger than normal side chain at position 530; residues 529 to 533 all proved important for the peroxidase as well as the cyclooxygenase activity, and Phe-529 in particular was critical for structure and catalysis. 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 bigger the group put at that position, the worse the enzyme binds its substrate. organism: Enzyme tissue_or_cell_type: Recombinant prostaglandin endoperoxide H synthase-1 experimental_model: Five further substitutions at Ser-530 and substitutions at adjoining residues, expressed transiently in cos-1 cells limitations: Tests the steric hypothesis by varying the bulk systematically rather than with one mutant. Transient expression in a heterologous cell line. exposure: A graded series of side chains at position 530, plus substitutions at Phe-529, Leu-531, Lys-532 and Gly-533 evidence_span: {"source_cache": "artifacts/aspirin-research/1601897.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "616cbc367eb38194b858872cbf91108baa3b1dec7aa039a40f69a29fa7157c2d", "start_char": 0, "end_char": 1744, "text_sha256": "616cbc367eb38194b858872cbf91108baa3b1dec7aa039a40f69a29fa7157c2d"} [asa-p1601897] Prostaglandin endoperoxide synthase. The aspirin acetylation region. (1992). https://pubmed.ncbi.nlm.nih.gov/1601897/ DOI: 10.1016/s0021-9258(19)49852-9
    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.

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