{"id":"00c31034-ec9b-5b36-a332-c95ad69ca037","stable_key":"09b23d0d-35e2-51ff-b1aa-b4f9227e4fa2:isoleucine-bckdk-brake","predicate":"inhibits_via_phosphorylation","statement":"BCKDK phosphorylates BCKDH E1-alpha; inactivating human BCKDK variants reduced E1-alpha phosphorylation and circulating BCAAs.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"c768360b-d011-506f-bf73-0e3821a90a2c","mechanism_event_label":"A kinase normally slows amino-acid breakdown.","subject":{"id":"a6cc94c2-b7e9-5963-bc93-e7fe7edbba0d","slug":"bckdk","display_name":"Human branched-chain ketoacid dehydrogenase kinase / BCKDK","entity_type_key":"protein"},"object":{"id":"f77ac9db-cdaf-5b43-a2bc-a5a54e2aa26c","slug":"human-bckdh-complex","display_name":"Human branched-chain alpha-ketoacid dehydrogenase complex","entity_type_key":"protein_complex"},"evidence_count":1,"mechanism_event":{"id":"c768360b-d011-506f-bf73-0e3821a90a2c","stable_key":"09b23d0d-35e2-51ff-b1aa-b4f9227e4fa2:isoleucine-bckdk-brake-event","event_type":"observed_relationship","label":"A kinase normally slows amino-acid breakdown.","description":"BCKDK phosphorylates BCKDH E1-alpha; inactivating human BCKDK variants reduced E1-alpha phosphorylation and circulating BCAAs.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a6cc94c2-b7e9-5963-bc93-e7fe7edbba0d","slug":"bckdk","display_name":"Human branched-chain ketoacid dehydrogenase kinase / BCKDK","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f77ac9db-cdaf-5b43-a2bc-a5a54e2aa26c","slug":"human-bckdh-complex","display_name":"Human branched-chain alpha-ketoacid dehydrogenase complex","entity_type_key":"protein_complex"},"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":"29e3916c-76ec-50fe-a9b7-177cfec8a7c8","slug":"bckdha","display_name":"Branched-chain ketoacid dehydrogenase E1 alpha / BCKDHA","entity_type_key":"protein"},"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":"Human families with biallelic BCKDK variants and supporting mouse experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This is a rare genetic syndrome, not a general explanation for autism.","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 kinase normally slows amino-acid breakdown.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22956686/ · DOI 10.1126/science.1224631","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":"217604de-874d-5238-8aaf-73c63b2425c8","evidence_kind":"source_excerpt","locator":"Lines 258-264","start_line":258,"end_line":264,"excerpt":"## isoleucine-bckdk-brake\nA kinase normally slows amino-acid breakdown.\nBCKDK phosphorylates BCKDH E1-alpha; inactivating human BCKDK variants reduced E1-alpha phosphorylation and circulating BCAAs.\nModel: Human families with biallelic BCKDK variants and supporting mouse experiments.\nLimitations: This is a rare genetic syndrome, not a general explanation for autism.\nEvidence access: Primary abstract\nMutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22956686/ · DOI 10.1126/science.1224631","model_system":"Human families with biallelic BCKDK variants and supporting mouse experiments.","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}