{"id":"f9daf639-7022-5d72-b6dd-87ebf0c46a38","stable_key":"10aa417f-4b03-599f-a453-4aa09edeb27c:alanine-pdac-mpc","predicate":"increases_dependence_on","statement":"UK-5099 inhibition of mitochondrial pyruvate transport reduced alanine synthesis/secretion and increased uptake of extracellular alanine; alanine supplementation restored intracellular levels.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"a0c614c2-c1c7-544b-b5ea-5ded6c9268ed","mechanism_event_label":"When pyruvate cannot reach the synthesis compartment, imported alanine becomes more important.","subject":{"id":"dbe747b0-cfbc-5fff-b35b-aff03ba7b941","slug":"human-pdac-mpc-inhibition","display_name":"Mitochondrial pyruvate carrier inhibition in human PDAC","entity_type_key":"cellular_process"},"object":{"id":"ebdc4461-c059-563e-88b0-422c21fdaa25","slug":"alanine","display_name":"L-Alanine","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"a0c614c2-c1c7-544b-b5ea-5ded6c9268ed","stable_key":"10aa417f-4b03-599f-a453-4aa09edeb27c:alanine-pdac-mpc-event","event_type":"observed_relationship","label":"When pyruvate cannot reach the synthesis compartment, imported alanine becomes more important.","description":"UK-5099 inhibition of mitochondrial pyruvate transport reduced alanine synthesis/secretion and increased uptake of extracellular alanine; alanine supplementation restored intracellular levels.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"dbe747b0-cfbc-5fff-b35b-aff03ba7b941","slug":"human-pdac-mpc-inhibition","display_name":"Mitochondrial pyruvate carrier inhibition in human PDAC","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ebdc4461-c059-563e-88b0-422c21fdaa25","slug":"alanine","display_name":"L-Alanine","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"dc2dabc7-ffca-5b5f-8b10-220798264e46","slug":"human-mpc-complex","display_name":"Human mitochondrial pyruvate carrier MPC1/MPC2","entity_type_key":"protein_complex"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"59baef49-fed8-5b6f-90ca-b8efdf021608","slug":"gpt2","display_name":"Human mitochondrial alanine aminotransferase / GPT2","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"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":4,"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":"Human PDAC cultures; MPC inhibitor and isotope tracing.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A pharmacological perturbation is not evidence that usual alanine intake bypasses every mitochondrial defect.","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":"When pyruvate cannot reach the synthesis compartment, imported alanine becomes more important.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959","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":"757dd00a-46d3-5d81-9934-cb92721ece13","evidence_kind":"source_excerpt","locator":"Lines 200-206","start_line":200,"end_line":206,"excerpt":"## alanine-pdac-mpc\nWhen pyruvate cannot reach the synthesis compartment, imported alanine becomes more important.\nUK-5099 inhibition of mitochondrial pyruvate transport reduced alanine synthesis/secretion and increased uptake of extracellular alanine; alanine supplementation restored intracellular levels.\nModel: Human PDAC cultures; MPC inhibitor and isotope tracing.\nLimitations: A pharmacological perturbation is not evidence that usual alanine intake bypasses every mitochondrial defect.\nEvidence access: Primary full text\nSelective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959","model_system":"Human PDAC cultures; MPC inhibitor and isotope tracing.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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