{"id":"274293f6-4cd9-55f5-b683-148e56842532","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-sig-delta-te-competitive","predicate":"competitively-inhibits","statement":"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.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"cf79055b-fe69-53fb-aee5-f03f8f4c958d","mechanism_event_label":"Kinetic measurements in this study indicated competition between this compound and arachidonic acid at 5-lipoxygenase.","subject":{"id":"56c5cd15-b521-587d-a063-1cfd03644b46","slug":"delta-tocotrienol","display_name":"Delta-tocotrienol","entity_type_key":"small_molecule"},"object":{"id":"c9794ec0-addc-51de-b505-3e54fcedc94d","slug":"alox5","display_name":"Arachidonate 5-lipoxygenase (ALOX5)","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"cf79055b-fe69-53fb-aee5-f03f8f4c958d","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-sig-delta-te-competitive-event","event_type":"biochemical_relationship","label":"Kinetic measurements in this study indicated competition between this compound and arachidonic acid at 5-lipoxygenase.","description":"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.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"39f9446f-52a6-502d-b507-91137726f82c","slug":"arachidonic-acid","display_name":"AA","entity_type_key":"small_molecule"},"role":"varied competing substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"assay cofactor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"56c5cd15-b521-587d-a063-1cfd03644b46","slug":"delta-tocotrienol","display_name":"Delta-tocotrienol","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"c9794ec0-addc-51de-b505-3e54fcedc94d","slug":"alox5","display_name":"Arachidonate 5-lipoxygenase (ALOX5)","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human recombinant 5-LOX oxygen-electrode initial-rate kinetics","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"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.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"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.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin E research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-e","display_name":"Vitamin E","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Kinetic measurements in this study indicated competition between this compound and arachidonic acid at 5-lipoxygenase.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cell-free enzyme","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"39c42102-8ef7-579b-9bac-6d9ae4619897","evidence_kind":"source_excerpt","locator":"Lines 1063-1074","start_line":1063,"end_line":1074,"excerpt":"### e-sig-delta-te-competitive\nPark 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.\nCondition category: normal\nnutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Kinetic measurements in this study indicated competition between this compound and arachidonic acid at 5-lipoxygenase.\norganism: Homo sapiens\ntissue_or_cell_type: Cell-free enzyme\nexperimental_model: Human recombinant 5-LOX oxygen-electrode initial-rate kinetics\nlimitations: 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.\nexposure: 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.\ncross_nutrient: false\n[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","model_system":"Human recombinant 5-LOX oxygen-electrode initial-rate kinetics","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study 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","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"3ac41dba-4727-5116-a556-ac3bbb0dc41c","stable_key":"import-e0ea2d6a-7429-5e9f-b774-41e5e3288da3","title":"Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. 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