{"id":"3472c852-d16a-5980-9eb1-c2bd9b9f62a1","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-sig-alpha-acid-leukocyte-lox","predicate":"inhibits","statement":"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.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"5905f196-cacd-5bb2-825e-278be9637e1b","mechanism_event_label":"The alpha-tocopherol metabolite reduced leukotriene-pathway enzyme output in isolated human immune cells.","subject":{"id":"b219b4cc-6e84-5190-b04d-a6c59861b8df","slug":"alpha-13-carboxychromanol","display_name":"Alpha-tocopherol-13′-carboxychromanol","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":"5905f196-cacd-5bb2-825e-278be9637e1b","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-sig-alpha-acid-leukocyte-lox-event","event_type":"biochemical_relationship","label":"The alpha-tocopherol metabolite reduced leukotriene-pathway enzyme output in isolated human immune cells.","description":"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.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"39f9446f-52a6-502d-b507-91137726f82c","slug":"arachidonic-acid","display_name":"AA","entity_type_key":"small_molecule"},"role":"lipid substrate of 5-LO","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b219b4cc-6e84-5190-b04d-a6c59861b8df","slug":"alpha-13-carboxychromanol","display_name":"Alpha-tocopherol-13′-carboxychromanol","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"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":2,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Primary human PMNL and recombinant enzyme, Table 1","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"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.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Potency cannot be equated with oral vitamin E dosing. 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