Component

Arachidonate 5-lipoxygenase (ALOX5)

Human 5-lipoxygenase; recombinant enzyme and cellular protein distinguished in each claim context.

9 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. Alpha-tocopherol-13′-carboxychromanol inhibited 5-LO product formation in activated human polymorphonuclear leukocytes with an IC50 of approximately 0.08 µM, compared with 0.27 µM for isolated recombinant human 5-LO.

    Alpha-tocopherol-13′-carboxychromanol → Arachidonate 5-lipoxygenase (ALOX5) source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    experimental_model
    Primary human PMNL and recombinant enzyme, Table 1
    exposure
    10 min compound pretreatment at 37°C; PMNL in PBS pH 7.4, 1 mg/mL glucose and 1 mM CaCl2, stimulated with 2.5 µM A23187 and/or 20 µM arachidonic acid for 10 min; IC50 80 nM.
    limitations
    Potency cannot be equated with oral vitamin E dosing. The activated leukocyte IC50 differs greatly from parent alpha-tocopherol and from other laboratories’ assay results.
    nutrient_topic
    Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
    organism
    Homo sapiens
    plain_language
    The alpha-tocopherol metabolite reduced leukotriene-pathway enzyme output in isolated human immune cells.
    primary_references
    [pein2018] Endogenous metabolites of vitamin E limit inflammation by targeting 5-lipoxygenase. (2018). https://pubmed.ncbi.nlm.nih.gov/30237488/ DOI: 10.1038/s41467-018-06158-5
    tissue_or_cell_type
    Isolated blood polymorphonuclear leukocytes and cell-free enzyme

    Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1011–1022

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human PMNL and recombinant enzyme, Table 1 · source_derived_draft · unverified_draft

    ### e-sig-alpha-acid-leukocyte-lox Alpha-tocopherol-13′-carboxychromanol inhibited 5-LO product formation in activated human polymorphonuclear leukocytes with an IC50 of approximately 0.08 µM, compared with 0.27 µM for isolated recombinant human 5-LO. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The alpha-tocopherol metabolite reduced leukotriene-pathway enzyme output in isolated human immune cells. organism: Homo sapiens tissue_or_cell_type: Isolated blood polymorphonuclear leukocytes and cell-free enzyme experimental_model: Primary human PMNL and recombinant enzyme, Table 1 limitations: Potency cannot be equated with oral vitamin E dosing. The activated leukocyte IC50 differs greatly from parent alpha-tocopherol and from other laboratories’ assay results. exposure: 10 min compound pretreatment at 37°C; PMNL in PBS pH 7.4, 1 mg/mL glucose and 1 mM CaCl2, stimulated with 2.5 µM A23187 and/or 20 µM arachidonic acid for 10 min; IC50 80 nM. cross_nutrient: false [pein2018] Endogenous metabolites of vitamin E limit inflammation by targeting 5-lipoxygenase. (2018). https://pubmed.ncbi.nlm.nih.gov/30237488/ DOI: 10.1038/s41467-018-06158-5
    Complete structured claim and evidence

  2. Park and colleagues classified Delta-tocopherol-13′-carboxychromanol as a competitive inhibitor of human recombinant 5-LOX, with Ki 1.6 µM; oxygen-consumption kinetics showed increased apparent substrate requirement without an apparent decrease in Vmax.

    Delta-tocopherol-13′-carboxychromanol → Arachidonate 5-lipoxygenase (ALOX5) source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    experimental_model
    Human recombinant 5-LOX oxygen-electrode initial-rate kinetics
    exposure
    10 min inhibitor preincubation; arachidonic acid 5–50 µM in 50 mM Tris pH 7.4 and 0.4 mM CaCl2; reported substrate Km 2.1 µM.
    limitations
    Kinetic classification is not a solved binding structure. The delta-tocotrienol metabolite result conflicts with Pein’s allosteric interpretation; differing IC50 values alone are not treated as conflicts.
    nutrient_topic
    Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
    organism
    Homo sapiens
    plain_language
    Kinetic measurements in this study indicated competition between this compound and arachidonic acid at 5-lipoxygenase.
    primary_references
    [park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. (2022). https://pubmed.ncbi.nlm.nih.gov/34710615/ DOI: 10.1016/j.jnutbio.2021.108884
    tissue_or_cell_type
    Cell-free enzyme

    Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1050–1061

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant 5-LOX oxygen-electrode initial-rate kinetics · source_derived_draft · unverified_draft

    ### e-sig-delta-acid-competitive Park and colleagues classified Delta-tocopherol-13′-carboxychromanol as a competitive inhibitor of human recombinant 5-LOX, with Ki 1.6 µM; oxygen-consumption kinetics showed increased apparent substrate requirement without an apparent decrease in Vmax. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Kinetic measurements in this study indicated competition between this compound and arachidonic acid at 5-lipoxygenase. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Human recombinant 5-LOX oxygen-electrode initial-rate kinetics limitations: Kinetic classification is not a solved binding structure. The delta-tocotrienol metabolite result conflicts with Pein’s allosteric interpretation; differing IC50 values alone are not treated as conflicts. exposure: 10 min inhibitor preincubation; arachidonic acid 5–50 µM in 50 mM Tris pH 7.4 and 0.4 mM CaCl2; reported substrate Km 2.1 µM. cross_nutrient: false [park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. (2022). https://pubmed.ncbi.nlm.nih.gov/34710615/ DOI: 10.1016/j.jnutbio.2021.108884
    Complete structured claim and evidence

  3. Delta-tocopherol-13′-carboxychromanol inhibited human recombinant 5-LOX with IC50 0.5–1 µM in a hydroperoxide-sensitive FOX assay; parent alpha-, gamma- and delta-tocopherols did not inhibit at 50 µM.

    Delta-tocopherol-13′-carboxychromanol → Arachidonate 5-lipoxygenase (ALOX5) source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    experimental_model
    Human recombinant 5-LOX and FOX endpoint
    exposure
    4 min preincubation; arachidonic acid 75 µM; FOX absorbance at 560 and 575 nm.
    limitations
    FOX reports oxidation products, not binding-site structure. Potency depends on assay conditions; later papers use other assays.
    nutrient_topic
    Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
    organism
    Homo sapiens
    plain_language
    The long-chain metabolite inhibited the isolated leukotriene-producing enzyme much more strongly than the parent tocopherols in this assay.
    primary_references
    [jiang2011] Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively. (2011). https://pubmed.ncbi.nlm.nih.gov/21169551/ DOI: 10.4049/jimmunol.1002342
    tissue_or_cell_type
    Cell-free enzyme

    Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 920–931

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant 5-LOX and FOX endpoint · source_derived_draft · unverified_draft

    ### e-sig-delta-acid-lox Delta-tocopherol-13′-carboxychromanol inhibited human recombinant 5-LOX with IC50 0.5–1 µM in a hydroperoxide-sensitive FOX assay; parent alpha-, gamma- and delta-tocopherols did not inhibit at 50 µM. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The long-chain metabolite inhibited the isolated leukotriene-producing enzyme much more strongly than the parent tocopherols in this assay. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Human recombinant 5-LOX and FOX endpoint limitations: FOX reports oxidation products, not binding-site structure. Potency depends on assay conditions; later papers use other assays. exposure: 4 min preincubation; arachidonic acid 75 µM; FOX absorbance at 560 and 575 nm. cross_nutrient: false [jiang2011] Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively. (2011). https://pubmed.ncbi.nlm.nih.gov/21169551/ DOI: 10.4049/jimmunol.1002342
    Complete structured claim and evidence

  4. Pein and colleagues interpreted delta-tocotrienol-13′-carboxychromanol inhibition of human 5-LO as reversible and allosteric: activity inhibition persisted when arachidonic acid was varied, and immobilized metabolite captured the enzyme despite excess arachidonic acid.

    Delta-tocotrienol-13′-carboxychromanol → Arachidonate 5-lipoxygenase (ALOX5) source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    experimental_model
    Purified human 5-LO; substrate variation, dilution and immobilized-ligand pull-down
    exposure
    Purified 5-LO 0.5 µg in PBS pH 7.4, EDTA 1 mM and ATP 1 mM; 10 min compound preincubation at 4°C, then 5–80 µM arachidonic acid and 2 mM CaCl2 at 37°C. Reported IC50 35–40 nM; pull-down competitor arachidonic acid 100 µM.
    limitations
    Binding-site assignment combines biochemical evidence with docking and mutagenesis, not a solved inhibitor-bound structure. Park 2022 explicitly disputes the noncompetitive interpretation.
    nutrient_topic
    Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
    organism
    Homo sapiens
    plain_language
    One study concluded that this tocotrienol metabolite inhibits 5-lipoxygenase at a site distinct from the usual fatty-acid binding site.
    primary_references
    [pein2018] Endogenous metabolites of vitamin E limit inflammation by targeting 5-lipoxygenase. (2018). https://pubmed.ncbi.nlm.nih.gov/30237488/ DOI: 10.1038/s41467-018-06158-5
    tissue_or_cell_type
    Cell-free enzyme

    Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1024–1035

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human 5-LO; substrate variation, dilution and immobilized-ligand pull-down · source_derived_draft · unverified_draft

    ### e-sig-delta-te-acid-allosteric Pein and colleagues interpreted delta-tocotrienol-13′-carboxychromanol inhibition of human 5-LO as reversible and allosteric: activity inhibition persisted when arachidonic acid was varied, and immobilized metabolite captured the enzyme despite excess arachidonic acid. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: One study concluded that this tocotrienol metabolite inhibits 5-lipoxygenase at a site distinct from the usual fatty-acid binding site. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Purified human 5-LO; substrate variation, dilution and immobilized-ligand pull-down limitations: Binding-site assignment combines biochemical evidence with docking and mutagenesis, not a solved inhibitor-bound structure. Park 2022 explicitly disputes the noncompetitive interpretation. exposure: Purified 5-LO 0.5 µg in PBS pH 7.4, EDTA 1 mM and ATP 1 mM; 10 min compound preincubation at 4°C, then 5–80 µM arachidonic acid and 2 mM CaCl2 at 37°C. Reported IC50 35–40 nM; pull-down competitor arachidonic acid 100 µM. cross_nutrient: false [pein2018] Endogenous metabolites of vitamin E limit inflammation by targeting 5-lipoxygenase. (2018). https://pubmed.ncbi.nlm.nih.gov/30237488/ DOI: 10.1038/s41467-018-06158-5
    Complete structured claim and evidence

  5. Park and colleagues classified Delta-tocotrienol-13′-carboxychromanol as a competitive inhibitor of human recombinant 5-LOX, with Ki 0.8 µM; oxygen-consumption kinetics showed increased apparent substrate requirement without an apparent decrease in Vmax.

    Delta-tocotrienol-13′-carboxychromanol → Arachidonate 5-lipoxygenase (ALOX5) source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    experimental_model
    Human recombinant 5-LOX oxygen-electrode initial-rate kinetics
    exposure
    10 min inhibitor preincubation; arachidonic acid 5–50 µM in 50 mM Tris pH 7.4 and 0.4 mM CaCl2; reported substrate Km 2.1 µM.
    limitations
    Kinetic classification is not a solved binding structure. The delta-tocotrienol metabolite result conflicts with Pein’s allosteric interpretation; differing IC50 values alone are not treated as conflicts.
    nutrient_topic
    Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
    organism
    Homo sapiens
    plain_language
    Kinetic measurements in this study indicated competition between this compound and arachidonic acid at 5-lipoxygenase.
    primary_references
    [park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. (2022). https://pubmed.ncbi.nlm.nih.gov/34710615/ DOI: 10.1016/j.jnutbio.2021.108884
    tissue_or_cell_type
    Cell-free enzyme

    Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1037–1048

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant 5-LOX oxygen-electrode initial-rate kinetics · source_derived_draft · unverified_draft

    ### e-sig-delta-te-acid-competitive Park and colleagues classified Delta-tocotrienol-13′-carboxychromanol as a competitive inhibitor of human recombinant 5-LOX, with Ki 0.8 µM; oxygen-consumption kinetics showed increased apparent substrate requirement without an apparent decrease in Vmax. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Kinetic measurements in this study indicated competition between this compound and arachidonic acid at 5-lipoxygenase. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Human recombinant 5-LOX oxygen-electrode initial-rate kinetics limitations: Kinetic classification is not a solved binding structure. The delta-tocotrienol metabolite result conflicts with Pein’s allosteric interpretation; differing IC50 values alone are not treated as conflicts. exposure: 10 min inhibitor preincubation; arachidonic acid 5–50 µM in 50 mM Tris pH 7.4 and 0.4 mM CaCl2; reported substrate Km 2.1 µM. cross_nutrient: false [park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. (2022). https://pubmed.ncbi.nlm.nih.gov/34710615/ DOI: 10.1016/j.jnutbio.2021.108884
    Complete structured claim and evidence

  6. Park and colleagues classified Delta-tocotrienol as a competitive inhibitor of human recombinant 5-LOX, with Ki 2.2 µM; oxygen-consumption kinetics showed increased apparent substrate requirement without an apparent decrease in Vmax.

    Delta-tocotrienol → Arachidonate 5-lipoxygenase (ALOX5) source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    experimental_model
    Human recombinant 5-LOX oxygen-electrode initial-rate kinetics
    exposure
    10 min inhibitor preincubation; arachidonic acid 5–50 µM in 50 mM Tris pH 7.4 and 0.4 mM CaCl2; reported substrate Km 2.1 µM.
    limitations
    Kinetic classification is not a solved binding structure. The delta-tocotrienol metabolite result conflicts with Pein’s allosteric interpretation; differing IC50 values alone are not treated as conflicts.
    nutrient_topic
    Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
    organism
    Homo sapiens
    plain_language
    Kinetic measurements in this study indicated competition between this compound and arachidonic acid at 5-lipoxygenase.
    primary_references
    [park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. (2022). https://pubmed.ncbi.nlm.nih.gov/34710615/ DOI: 10.1016/j.jnutbio.2021.108884
    tissue_or_cell_type
    Cell-free enzyme

    Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1063–1074

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant 5-LOX oxygen-electrode initial-rate kinetics · source_derived_draft · unverified_draft

    ### e-sig-delta-te-competitive Park and colleagues classified Delta-tocotrienol as a competitive inhibitor of human recombinant 5-LOX, with Ki 2.2 µM; oxygen-consumption kinetics showed increased apparent substrate requirement without an apparent decrease in Vmax. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Kinetic measurements in this study indicated competition between this compound and arachidonic acid at 5-lipoxygenase. organism: Homo sapiens tissue_or_cell_type: Cell-free enzyme experimental_model: Human recombinant 5-LOX oxygen-electrode initial-rate kinetics limitations: Kinetic classification is not a solved binding structure. The delta-tocotrienol metabolite result conflicts with Pein’s allosteric interpretation; differing IC50 values alone are not treated as conflicts. exposure: 10 min inhibitor preincubation; arachidonic acid 5–50 µM in 50 mM Tris pH 7.4 and 0.4 mM CaCl2; reported substrate Km 2.1 µM. cross_nutrient: false [park2022] Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase. (2022). https://pubmed.ncbi.nlm.nih.gov/34710615/ DOI: 10.1016/j.jnutbio.2021.108884
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Delta-tocopherol pretreatment largely prevented A23187-induced redistribution of 5-LOX from cytosolic to nuclear fractions in differentiated HL-60 cells.

    Delta-tocopherol → 5-Lipoxygenase nuclear translocation source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    experimental_model
    DMSO-differentiated human HL-60 neutrophil-like cells; fractionation and immunoblot
    exposure
    50 µM delta-tocopherol for 10 min followed by 2.5 µM A23187 for 15 min.
    limitations
    Fractionation is a localization assay, not proof of direct enzyme inhibition; purified 5-LOX was unaffected by tocopherols at 50 µM in this paper.
    nutrient_topic
    Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
    organism
    Homo sapiens
    plain_language
    Delta-tocopherol kept much of the enzyme from moving to the cell location associated with leukotriene production.
    primary_references
    [jiang2011] Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively. (2011). https://pubmed.ncbi.nlm.nih.gov/21169551/ DOI: 10.4049/jimmunol.1002342
    tissue_or_cell_type
    Neutrophil-like leukemia-derived cell culture

    Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 907–918

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · DMSO-differentiated human HL-60 neutrophil-like cells; fractionation and immunoblot · source_derived_draft · unverified_draft

    ### e-sig-delta-lox-translocation Delta-tocopherol pretreatment largely prevented A23187-induced redistribution of 5-LOX from cytosolic to nuclear fractions in differentiated HL-60 cells. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Delta-tocopherol kept much of the enzyme from moving to the cell location associated with leukotriene production. organism: Homo sapiens tissue_or_cell_type: Neutrophil-like leukemia-derived cell culture experimental_model: DMSO-differentiated human HL-60 neutrophil-like cells; fractionation and immunoblot limitations: Fractionation is a localization assay, not proof of direct enzyme inhibition; purified 5-LOX was unaffected by tocopherols at 50 µM in this paper. exposure: 50 µM delta-tocopherol for 10 min followed by 2.5 µM A23187 for 15 min. cross_nutrient: false [jiang2011] Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively. (2011). https://pubmed.ncbi.nlm.nih.gov/21169551/ DOI: 10.4049/jimmunol.1002342
    Complete structured claim and evidence

  2. 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.

    Aspirin / acetylsalicylic acid → Aspirin-triggered 15R-epimeric lipoxins source_derived_draftungraded
    Experimental context and source evidence
    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"}
    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
    Complete structured claim and evidence

  3. 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
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