Component

Diversion of unmetabolised arachidonate into the 5-lipoxygenase pathway

Diversion of unmetabolised arachidonate into the 5-lipoxygenase pathway. Species, exposure and limitations are retained in each linked claim.

3 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 adverse effect of aspirin in asthmatics is often attributed to inhibition of the synthesis and release of defensive modulatory endogenous prostaglandins in the lungs, removing their negative feedback on allergic mediator release, and in addition work suggests diversion of arachidonic acid metabolism via the lipoxygenase pathway after cyclooxygenase inhibition, leading to formation of hydroperoxy acids and leukotrienes whose accumulation in sensitive individuals could explain the mechanism of aspirin-induced asthma.

    Aspirin / acetylsalicylic acid → Diversion of unmetabolised arachidonate into the 5-lipoxygenase pathway source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/aspirin-research/6113615.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "184fc232146a3837f396109d951c9755155f181c524a3ffaa330645138d8a616", "start_char": 0, "end_char": 2083, "text_sha256": "184fc232146a3837f396109d951c9755155f181c524a3ffaa330645138d8a616"}
    experimental_model
    Review of arachidonate metabolism in airway hyperreactivity and aspirin-induced asthma
    exposure
    Cyclooxygenase inhibition and the proposed diversion of arachidonate into the lipoxygenase pathway
    limitations
    A review from 1981 setting out the shunting hypothesis. It is recorded as the proposal that later work tested, not as evidence that the proposal is right.
    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 standard explanation: block one pathway and the raw material spills into another that makes bronchoconstrictors.
    primary_references
    [asa-p6113615] Lipoxygenase pathway and hydroperoxy acids: possible relevance to aspirin-induced asthma and hyperirritability of airways in asthmatics. (1981). https://pubmed.ncbi.nlm.nih.gov/6113615/ DOI: 10.1016/0161-4630(81)90097-5
    tissue_or_cell_type
    Airway

    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 546–557

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of arachidonate metabolism in airway hyperreactivity and aspirin-induced asthma · source_derived_draft · unverified_draft

    ### asa-shunting-proposed The adverse effect of aspirin in asthmatics is often attributed to inhibition of the synthesis and release of defensive modulatory endogenous prostaglandins in the lungs, removing their negative feedback on allergic mediator release, and in addition work suggests diversion of arachidonic acid metabolism via the lipoxygenase pathway after cyclooxygenase inhibition, leading to formation of hydroperoxy acids and leukotrienes whose accumulation in sensitive individuals could explain the mechanism of aspirin-induced asthma. 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 standard explanation: block one pathway and the raw material spills into another that makes bronchoconstrictors. organism: Human tissue_or_cell_type: Airway experimental_model: Review of arachidonate metabolism in airway hyperreactivity and aspirin-induced asthma limitations: A review from 1981 setting out the shunting hypothesis. It is recorded as the proposal that later work tested, not as evidence that the proposal is right. exposure: Cyclooxygenase inhibition and the proposed diversion of arachidonate into the lipoxygenase pathway evidence_span: {"source_cache": "artifacts/aspirin-research/6113615.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "184fc232146a3837f396109d951c9755155f181c524a3ffaa330645138d8a616", "start_char": 0, "end_char": 2083, "text_sha256": "184fc232146a3837f396109d951c9755155f181c524a3ffaa330645138d8a616"} [asa-p6113615] Lipoxygenase pathway and hydroperoxy acids: possible relevance to aspirin-induced asthma and hyperirritability of airways in asthmatics. (1981). https://pubmed.ncbi.nlm.nih.gov/6113615/ DOI: 10.1016/0161-4630(81)90097-5
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Excretion of leukotriene E4 was increased by a mean of 361% during aspirin-induced asthma episodes, but the degree of increase for individual patients did not correlate with the degree of bronchospasm or with inhibition of platelet thromboxane B2 formation, so although endogenous synthesis of potent bronchoconstrictor leukotrienes increases during aspirin-induced bronchospasm it appears unlikely that direct shunting of unmetabolised arachidonate into leukotriene synthesis represents the mechanism of aspirin-induced asthma.

    Urinary leukotriene E4 excretion → Aspirin-induced bronchospasm source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/aspirin-research/1309376.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "115a13f9e08205c2b6ea376e5a1fcb90cc6887b277041acc114908c7d85f6e05", "start_char": 0, "end_char": 1427, "text_sha256": "115a13f9e08205c2b6ea376e5a1fcb90cc6887b277041acc114908c7d85f6e05"}
    experimental_model
    Urinary leukotriene E4 measured during aspirin-induced asthma episodes across a range of provoking doses
    exposure
    Aspirin doses from 30 to 365 milligrams in individual aspirin-sensitive patients
    limitations
    Tests the shunting hypothesis by asking whether the leukotriene rise tracks the bronchospasm, which it does not. Urinary leukotriene E4 is a whole-body measure rather than an airway one.
    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 leukotrienes do rise, but how much they rise says nothing about how badly the patient wheezes.
    primary_references
    [asa-p1309376] Increased excretion of leukotriene E4 during aspirin-induced asthma. (1992). https://pubmed.ncbi.nlm.nih.gov/1309376/
    tissue_or_cell_type
    Airway and urine

    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 559–570

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Urinary leukotriene E4 measured during aspirin-induced asthma episodes across a range of provoking doses · source_derived_draft · unverified_draft

    ### asa-shunting-does-not-track Excretion of leukotriene E4 was increased by a mean of 361% during aspirin-induced asthma episodes, but the degree of increase for individual patients did not correlate with the degree of bronchospasm or with inhibition of platelet thromboxane B2 formation, so although endogenous synthesis of potent bronchoconstrictor leukotrienes increases during aspirin-induced bronchospasm it appears unlikely that direct shunting of unmetabolised arachidonate into leukotriene synthesis represents the mechanism of aspirin-induced asthma. 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 leukotrienes do rise, but how much they rise says nothing about how badly the patient wheezes. organism: Human tissue_or_cell_type: Airway and urine experimental_model: Urinary leukotriene E4 measured during aspirin-induced asthma episodes across a range of provoking doses limitations: Tests the shunting hypothesis by asking whether the leukotriene rise tracks the bronchospasm, which it does not. Urinary leukotriene E4 is a whole-body measure rather than an airway one. exposure: Aspirin doses from 30 to 365 milligrams in individual aspirin-sensitive patients evidence_span: {"source_cache": "artifacts/aspirin-research/1309376.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "115a13f9e08205c2b6ea376e5a1fcb90cc6887b277041acc114908c7d85f6e05", "start_char": 0, "end_char": 1427, "text_sha256": "115a13f9e08205c2b6ea376e5a1fcb90cc6887b277041acc114908c7d85f6e05"} [asa-p1309376] Increased excretion of leukotriene E4 during aspirin-induced asthma. (1992). https://pubmed.ncbi.nlm.nih.gov/1309376/
    Complete structured claim and evidence

  2. 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