{"id":"15b536e5-9c5c-59c5-9669-bdaff8783efc","stable_key":"research:lpcat3-incorporation","predicate":"supports_formation_of","statement":"LPCAT3-mediated acyl incorporation contributes to arachidonoyl PE formation after fatty-acid activation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"literature_reviewed:direct_experimental","direction":"positive","is_public":true,"mechanism_event_id":"0b883f77-9a7b-5155-8bec-713597a262a7","mechanism_event_label":"Membrane incorporation follows fatty-acid activation.","subject":{"id":"2496e0b8-8358-5876-a21f-8ca13660d803","slug":"lpcat3","display_name":"LPCAT3","entity_type_key":"protein"},"object":{"id":"8aecea04-dba1-5226-8878-3c04d67bb8e9","slug":"arachidonoyl-pe","display_name":"PE-AA","entity_type_key":"lipid"},"evidence_count":1,"mechanism_event":{"id":"0b883f77-9a7b-5155-8bec-713597a262a7","stable_key":"research:lpcat3-incorporation","event_type":"lipid_synthesis","label":"Membrane incorporation follows fatty-acid activation.","description":"LPCAT3-mediated acyl incorporation contributes to arachidonoyl PE formation after fatty-acid activation.","status":"active","compartment":null,"participants":[{"entity":{"id":"d57c5904-b492-5a04-9162-429f368fafd2","slug":"arachidonoyl-coa","display_name":"arachidonoyl-CoA","entity_type_key":"small_molecule"},"role":"acyl_donor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"2496e0b8-8358-5876-a21f-8ca13660d803","slug":"lpcat3","display_name":"LPCAT3","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8aecea04-dba1-5226-8878-3c04d67bb8e9","slug":"arachidonoyl-pe","display_name":"PE-AA","entity_type_key":"lipid"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"cell_type","value_text":"Lung epithelial cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cell genetic perturbation, mouse lung epithelial Lpcat3 knockdown, redox lipidomics","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Substrate preference and ferroptosis dependence vary by cell.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"362c755e-1f77-5fee-9e10-431a271a2c75","evidence_kind":"curated_literature_summary","locator":"lines 1227-1237","start_line":1227,"end_line":1237,"excerpt":"## lpcat3-incorporation\n\nMembrane incorporation follows fatty-acid activation.\n\nLPCAT3-mediated acyl incorporation contributes to arachidonoyl PE formation after fatty-acid activation.\n\nOrganism: Mus musculus\nCell type: Lung epithelial cells\nExperimental model: Cell genetic perturbation, mouse lung epithelial Lpcat3 knockdown, redox lipidomics\nLimitations: Substrate preference and ferroptosis dependence vary by cell.\nPrimary reference: [Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis](https://pubmed.ncbi.nlm.nih.gov/27842066/)","model_system":"Cell genetic perturbation, mouse lung epithelial Lpcat3 knockdown, redox lipidomics","directness":"author_interpretation","verification_status":"secondary_verified","notes":"Curated summary; inspect the linked primary papers for original methods and results.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4f892f13-06ea-5199-a33c-a703f35c80ae","stable_key":"selenium-research-2026-09-17","title":"Selenium: literature corrections and mechanism additions","document_type":"curated_literature_review","citation_label":"Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually","file_path":"","sha256":"0b818b10c1c7120e5caf7f4d4019d7bd025d745692e424f515d3ef903c9ab7f3","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","review_status":"secondary_verified","notes":"Secondary curated summaries of primary experiments, with explicit models and limitations. Not archived primary full text."}}],"relations":[],"conflicts":[],"corrections":[{"id":"d47d5b8e-8380-5767-9b01-f7c4b1f02f64","title":"ACSL4 activation precedes LPCAT3-mediated lipid incorporation","kind":"contradiction","status":"corrected","why":"Initial diagram places PE esterification before LPCAT3; the second source already supplies the correct sequence.","resolution":"Preserve both diagrams and separate AA to AA-CoA to PE-AA steps.","created_at":"2026-09-17 07:19:34","record_type":"correction","display_label":"Correction history","record_url":"/corrections/d47d5b8e-8380-5767-9b01-f7c4b1f02f64","literature_review":{"revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1563,"end_line":1568,"papers":[{"paper_key":"kagan-2017","title":"Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis","url":"https://pubmed.ncbi.nlm.nih.gov/27842066/","doi":"10.1038/nchembio.2238","year":2017,"model":"Cell genetic perturbation, mouse lung epithelial Lpcat3 knockdown, redox lipidomics","summary":"ACSL4 activation precedes LPCAT3-mediated phospholipid incorporation."}]},"sides":[{"conflict_id":"d47d5b8e-8380-5767-9b01-f7c4b1f02f64","ordinal":0,"label":"Original preserved statement","revision_id":"1fa1ebde-141f-5d47-8a4f-ba87ff84a6c6","start_line":91,"end_line":91,"quote":"PUFA (arachidonoyl) → **ACSL4** → esterified into PE → **LPCAT3** → **ALOX15** or Fe²⁺-driven autoxidation → **PE-AA-OOH** in the membrane → GPX4 reduces it to PE-AA-OH. Knock out GPX4, drug it (RSL3, ML162 — which covalently alkylate the selenolate *because* it's the best nucleophile around), or starve it of Se → hydroperoxides propagate → membrane rupture → ferroptosis.","claim_id":null,"source_key":"molecular","source_title":"Selenium: the molecular cascade","claim_ids":[]},{"conflict_id":"d47d5b8e-8380-5767-9b01-f7c4b1f02f64","ordinal":1,"label":"Original preserved statement","revision_id":"4cec6304-35d7-5560-9133-e6ea689db838","start_line":111,"end_line":111,"quote":"AA ──ACSL4──► AA-CoA ──LPCAT3──► PE-AA ──ALOX15/PEBP1──► PE-AA-OOH","claim_id":null,"source_key":"corrections","source_title":"Selenium corrections and deep dive","claim_ids":[]},{"conflict_id":"d47d5b8e-8380-5767-9b01-f7c4b1f02f64","ordinal":2,"label":"Literature correction and experimental limits","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1563,"end_line":1568,"quote":"## ACSL4 activation precedes LPCAT3-mediated lipid incorporation\n\nInitial diagram places PE esterification before LPCAT3; the second source already supplies the correct sequence.\n\nPreserve both diagrams and separate AA to AA-CoA to PE-AA steps.\nPrimary reference: [Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis](https://pubmed.ncbi.nlm.nih.gov/27842066/)","claim_id":null,"source_key":"selenium-research-2026-09-17","source_title":"Selenium: literature corrections and mechanism additions","claim_ids":[]}]}],"research":{"topic":"Selenium scientific audit","plain_language":"Membrane incorporation follows fatty-acid activation.","evidence_scope":"direct_experimental","papers":[{"key":"kagan-2017","title":"Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis","url":"https://pubmed.ncbi.nlm.nih.gov/27842066/","doi":"10.1038/nchembio.2238","year":2017,"model":"Cell genetic perturbation, mouse lung epithelial Lpcat3 knockdown, redox lipidomics","summary":"ACSL4 activation precedes LPCAT3-mediated phospholipid incorporation."}]}}