{"id":"f23a6be8-581d-587c-8a28-83e93f5ad1da","stable_key":"09b23d0d-35e2-51ff-b1aa-b4f9227e4fa2:isoleucine-ppm1k-loss","predicate":"supports","statement":"Ppm1k loss abolished substrate-induced E1-alpha dephosphorylation and impaired BCAA catabolism in mice.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"77198237-5d6f-54c2-880f-d05079d7c489","mechanism_event_label":"Failure to release the brake can produce accumulation rather than shortage.","subject":{"id":"99746f7e-b7a4-5bc3-9a86-116719bc97a7","slug":"mouse-ppm1k","display_name":"Mouse BCKDH phosphatase PP2Cm / Ppm1k","entity_type_key":"protein"},"object":{"id":"c1070989-7131-54e7-8b72-4616821cbacc","slug":"mouse-substrate-bckdh-activation","display_name":"Substrate-induced BCKDH activation in mice","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"77198237-5d6f-54c2-880f-d05079d7c489","stable_key":"09b23d0d-35e2-51ff-b1aa-b4f9227e4fa2:isoleucine-ppm1k-loss-event","event_type":"observed_relationship","label":"Failure to release the brake can produce accumulation rather than shortage.","description":"Ppm1k loss abolished substrate-induced E1-alpha dephosphorylation and impaired BCAA catabolism in mice.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"99746f7e-b7a4-5bc3-9a86-116719bc97a7","slug":"mouse-ppm1k","display_name":"Mouse BCKDH phosphatase PP2Cm / Ppm1k","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"c1070989-7131-54e7-8b72-4616821cbacc","slug":"mouse-substrate-bckdh-activation","display_name":"Substrate-induced BCKDH activation in mice","entity_type_key":"cellular_process"},"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":""},{"entity":{"id":"a2674c2c-2729-555a-83e5-25b83409d787","slug":"mouse-bckdh-complex","display_name":"Mouse branched-chain alpha-ketoacid dehydrogenase complex","entity_type_key":"protein_complex"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"f707c753-cc8c-5f06-90be-bb3d73c60a18","slug":"leucine","display_name":"L-Leucine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"ae40617e-3df7-5d48-8dd2-f16a0d3a8a25","slug":"valine","display_name":"L-Valine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"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 abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Ppm1k-deficient mice and cultured cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Mouse MSUD-like phenotype is not a diagnosis of dietary BCAA excess.","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":"Failure to release the brake can produce accumulation rather than shortage.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19411760/ · DOI 10.1172/JCI38151","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":"d7fa3f72-6fde-5298-aab8-49b9686bd355","evidence_kind":"source_excerpt","locator":"Lines 282-288","start_line":282,"end_line":288,"excerpt":"## isoleucine-ppm1k-loss\nFailure to release the brake can produce accumulation rather than shortage.\nPpm1k loss abolished substrate-induced E1-alpha dephosphorylation and impaired BCAA catabolism in mice.\nModel: Ppm1k-deficient mice and cultured cells.\nLimitations: Mouse MSUD-like phenotype is not a diagnosis of dietary BCAA excess.\nEvidence access: Primary abstract\nProtein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19411760/ · DOI 10.1172/JCI38151","model_system":"Ppm1k-deficient mice and cultured cells.","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}