{"id":"1038aa61-a588-5238-83a8-26809ec6aad7","stable_key":"09b23d0d-35e2-51ff-b1aa-b4f9227e4fa2:isoleucine-restriction-gcn2-boundary","predicate":"improves_without","statement":"Liver-specific Gcn2 deletion did not prevent low-isoleucine improvements in glucose tolerance or body-composition measures.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"aead3ab6-a756-5fc5-b585-f30eb2c4fbaa","mechanism_event_label":"A common amino-acid stress sensor was dispensable in this liver/diet experiment.","subject":{"id":"59da00d5-9277-5068-9c49-775200ebb582","slug":"mouse-low-isoleucine-diet","display_name":"Experimentally reduced-isoleucine mouse diet","entity_type_key":"cellular_process"},"object":{"id":"3876a24a-f6fe-5900-8ce2-22525a4faacb","slug":"mouse-eif2ak4","display_name":"Mouse GCN2 / Eif2ak4","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"aead3ab6-a756-5fc5-b585-f30eb2c4fbaa","stable_key":"09b23d0d-35e2-51ff-b1aa-b4f9227e4fa2:isoleucine-restriction-gcn2-boundary-event","event_type":"observed_relationship","label":"A common amino-acid stress sensor was dispensable in this liver/diet experiment.","description":"Liver-specific Gcn2 deletion did not prevent low-isoleucine improvements in glucose tolerance or body-composition measures.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"59da00d5-9277-5068-9c49-775200ebb582","slug":"mouse-low-isoleucine-diet","display_name":"Experimentally reduced-isoleucine mouse diet","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"3876a24a-f6fe-5900-8ce2-22525a4faacb","slug":"mouse-eif2ak4","display_name":"Mouse GCN2 / Eif2ak4","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"c85b327e-f132-5d9a-8e4b-c2976fcc0373","slug":"isoleucine","display_name":"L-Isoleucine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse liver-specific Gcn2 knockout, twelve-day and three-week glucose tests.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Not equivalent to complete cellular starvation or loss of GCN2 in every tissue.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"isoleucine","display_name":"L-Isoleucine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A common amino-acid stress sensor was dispensable in this liver/diet experiment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33887198/ · DOI 10.1016/j.cmet.2021.03.025","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"8db4fcb9-d5fa-5c3e-b7be-50dfb09dd2d4","evidence_kind":"source_excerpt","locator":"Lines 402-408","start_line":402,"end_line":408,"excerpt":"## isoleucine-restriction-gcn2-boundary\nA common amino-acid stress sensor was dispensable in this liver/diet experiment.\nLiver-specific Gcn2 deletion did not prevent low-isoleucine improvements in glucose tolerance or body-composition measures.\nModel: Mouse liver-specific Gcn2 knockout, twelve-day and three-week glucose tests.\nLimitations: Not equivalent to complete cellular starvation or loss of GCN2 in every tissue.\nEvidence access: Primary full text\nThe adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33887198/ · DOI 10.1016/j.cmet.2021.03.025","model_system":"Mouse liver-specific Gcn2 knockout, twelve-day and three-week glucose tests.","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":"4b00f118-00fd-5cef-be97-13125eb958e9","stable_key":"import-09b23d0d-35e2-51ff-b1aa-b4f9227e4fa2","title":"L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"2058ff0da379586994e7fda6ae0086c60fa3173542bfaf1fb3871ad3e09f9c6c","revision_id":"f32192d4-9913-5d35-acbc-cf90ff17995e","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}