{"id":"3a21c0e8-d873-56b3-90d8-de98f7dc11f7","stable_key":"6cdb37aa-8998-5ea8-829d-4f995caf98fc:l-carnitine-etomoxir-coa","predicate":"depletes","statement":"High etomoxir exposure depleted free CoA and inhibited IL-4 macrophage polarization even without Cpt1a or Cpt2 expression.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"b2271df8-672d-5fc6-b3bf-45ff0369bdab","mechanism_event_label":"The experiment exposed a CoA-related off-target effect.","subject":{"id":"2414d192-9440-54eb-8ed9-d7fecd6552d7","slug":"etomoxir","display_name":"Etomoxir","entity_type_key":"small_molecule"},"object":{"id":"1fd8e85f-2596-5630-9ad8-bf31cee417a5","slug":"mouse-macrophage-free-coa","display_name":"Mouse macrophage free CoA pool","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"b2271df8-672d-5fc6-b3bf-45ff0369bdab","stable_key":"6cdb37aa-8998-5ea8-829d-4f995caf98fc:l-carnitine-etomoxir-coa-event","event_type":"observed_relationship","label":"The experiment exposed a CoA-related off-target effect.","description":"High etomoxir exposure depleted free CoA and inhibited IL-4 macrophage polarization even without Cpt1a or Cpt2 expression.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"2414d192-9440-54eb-8ed9-d7fecd6552d7","slug":"etomoxir","display_name":"Etomoxir","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1fd8e85f-2596-5630-9ad8-bf31cee417a5","slug":"mouse-macrophage-free-coa","display_name":"Mouse macrophage free CoA pool","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"4faa6456-aff8-59eb-9e3f-3326a436e401","slug":"coenzyme-a","display_name":"Coenzyme A","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"6e34c035-9371-578f-b799-fd2a14e9e40f","slug":"l-carnitine","display_name":"L-Carnitine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract and full-text genetic/pharmacologic experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse macrophages; pharmacologic exposure exceeding concentrations needed to inhibit CPT1.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Etomoxiryl-CoA formation was the proposed depletion mechanism; not evidence that carnitine depletes CoA.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-carnitine","display_name":"L-Carnitine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"The experiment exposed a CoA-related off-target effect.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Etomoxir Inhibits Macrophage Polarization by Disrupting CoA Homeostasis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30043752/ · DOI 10.1016/j.cmet.2018.06.001","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"fefd5685-de32-576d-88af-7991bdb54f13","evidence_kind":"source_excerpt","locator":"Lines 450-456","start_line":450,"end_line":456,"excerpt":"## l-carnitine-etomoxir-coa\nThe experiment exposed a CoA-related off-target effect.\nHigh etomoxir exposure depleted free CoA and inhibited IL-4 macrophage polarization even without Cpt1a or Cpt2 expression.\nModel: Mouse macrophages; pharmacologic exposure exceeding concentrations needed to inhibit CPT1.\nLimitations: Etomoxiryl-CoA formation was the proposed depletion mechanism; not evidence that carnitine depletes CoA.\nEvidence access: Primary abstract and full-text genetic/pharmacologic experiments\nEtomoxir Inhibits Macrophage Polarization by Disrupting CoA Homeostasis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30043752/ · DOI 10.1016/j.cmet.2018.06.001","model_system":"Mouse macrophages; pharmacologic exposure exceeding concentrations needed to inhibit CPT1.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"e2c9c42b-806a-55e2-abde-b0320ea94704","stable_key":"import-6cdb37aa-8998-5ea8-829d-4f995caf98fc","title":"L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; 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