{"id":"1258d74f-61fa-5850-af64-db564267ec91","stable_key":"10aa417f-4b03-599f-a453-4aa09edeb27c:alanine-beta-chronic-pdh","predicate":"changes","statement":"Prolonged alanine culture increased NMR-inferred pyruvate-dehydrogenase flux while reducing PDK2/PDK4 protein and cellular ATP.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"2b99043c-a085-5f73-bde9-54e8137c22d0","mechanism_event_label":"More flux through one metabolic step did not mean more stored ATP or stronger insulin release.","subject":{"id":"ebdc4461-c059-563e-88b0-422c21fdaa25","slug":"alanine","display_name":"L-Alanine","entity_type_key":"small_molecule"},"object":{"id":"a063f12f-6549-5276-9ccb-d77438a861a2","slug":"rat-brin-pdh-flux-atp","display_name":"PDH flux and ATP after prolonged alanine culture","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"2b99043c-a085-5f73-bde9-54e8137c22d0","stable_key":"10aa417f-4b03-599f-a453-4aa09edeb27c:alanine-beta-chronic-pdh-event","event_type":"observed_relationship","label":"More flux through one metabolic step did not mean more stored ATP or stronger insulin release.","description":"Prolonged alanine culture increased NMR-inferred pyruvate-dehydrogenase flux while reducing PDK2/PDK4 protein and cellular ATP.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"ebdc4461-c059-563e-88b0-422c21fdaa25","slug":"alanine","display_name":"L-Alanine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"a063f12f-6549-5276-9ccb-d77438a861a2","slug":"rat-brin-pdh-flux-atp","display_name":"PDH flux and ATP after prolonged alanine culture","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8b31e1bc-b2f9-5ecb-b91e-e08d2e4ac460","slug":"rat-pdk2","display_name":"Rat pyruvate dehydrogenase kinase 2 / Pdk2","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"d91dd205-0918-59b9-8a9d-25d496b2a830","slug":"rat-pdk4","display_name":"Rat pyruvate dehydrogenase kinase 4 / Pdk4","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"58b974f1-d389-5bf6-81cd-889c44442c42","slug":"atp","display_name":"ATP","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"91e6d4f5-fba1-542d-b68a-57cc28e1e425","slug":"pyruvate","display_name":"Pyruvate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Rat BRIN-BD11 tracing and protein measurements.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Concurrent changes are not a direct demonstration that PDK loss caused the ATP or secretion phenotype.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"alanine","display_name":"L-Alanine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"More flux through one metabolic step did not mean more stored ATP or stronger insulin release.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Prolonged L-alanine exposure induces changes in metabolism, Ca(2+) handling and desensitization of insulin secretion in clonal pancreatic beta-cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18702613/ · DOI 10.1042/CS20080138","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"3823e255-0655-5ad1-a881-1303bc61acaa","evidence_kind":"source_excerpt","locator":"Lines 416-422","start_line":416,"end_line":422,"excerpt":"## alanine-beta-chronic-pdh\nMore flux through one metabolic step did not mean more stored ATP or stronger insulin release.\nProlonged alanine culture increased NMR-inferred pyruvate-dehydrogenase flux while reducing PDK2/PDK4 protein and cellular ATP.\nModel: Rat BRIN-BD11 tracing and protein measurements.\nLimitations: Concurrent changes are not a direct demonstration that PDK loss caused the ATP or secretion phenotype.\nEvidence access: Primary abstract\nProlonged L-alanine exposure induces changes in metabolism, Ca(2+) handling and desensitization of insulin secretion in clonal pancreatic beta-cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18702613/ · DOI 10.1042/CS20080138","model_system":"Rat BRIN-BD11 tracing and protein measurements.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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