{"id":"1e986c62-ca66-5637-aad4-f00c933db78a","stable_key":"e37461ea-ea5d-5e2c-8091-138305f6dd70:l-aspartate-protein-scavenging-rescue","predicate":"restores_aspartate_availability","statement":"Bovine albumin supplementation restored aspartate and pyrimidine-related metabolites and partly rescued hypoxic growth in the tested KRAS-mutant human PDAC cultures.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"847b1700-942a-5e87-abb1-fbb1c9f5137e","mechanism_event_label":"Cells can obtain amino acids by digesting extracellular protein.","subject":{"id":"29baf29d-4a1c-51ba-9b58-75675eb9ab85","slug":"bovine-serum-albumin","display_name":"Bovine serum albumin","entity_type_key":"protein"},"object":{"id":"cce36e8f-9dc3-55e8-97dc-d91a538d3d6e","slug":"human-pdac-protein-derived-aspartate","display_name":"Aspartate supplied by protein scavenging in human PDAC cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"847b1700-942a-5e87-abb1-fbb1c9f5137e","stable_key":"e37461ea-ea5d-5e2c-8091-138305f6dd70:l-aspartate-protein-scavenging-rescue-event","event_type":"observed_relationship","label":"Cells can obtain amino acids by digesting extracellular protein.","description":"Bovine albumin supplementation restored aspartate and pyrimidine-related metabolites and partly rescued hypoxic growth in the tested KRAS-mutant human PDAC cultures.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"29baf29d-4a1c-51ba-9b58-75675eb9ab85","slug":"bovine-serum-albumin","display_name":"Bovine serum albumin","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"cce36e8f-9dc3-55e8-97dc-d91a538d3d6e","slug":"human-pdac-protein-derived-aspartate","display_name":"Aspartate supplied by protein scavenging in human PDAC cells","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"0a0923d3-72b7-5d6a-bf3a-5a7a3071a09b","slug":"l-aspartate","display_name":"L-Aspartate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"e619a420-21e3-5341-b54c-9da535c00549","slug":"human-pdac-macropinocytosis","display_name":"Macropinocytic protein scavenging by human PDAC cells","entity_type_key":"cellular_process"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"64cc3b93-3e99-5221-bd91-049d190e54c7","slug":"cad","display_name":"Human CAD multifunctional pyrimidine synthesis enzyme","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human MIA PaCa-2-centered hypoxic culture, albumin addition and macropinocytosis experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This is an extracellular protein-scavenging mechanism, not evidence of direct intact dietary protein delivery to a tumor.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-aspartate","display_name":"L-Aspartate","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Cells can obtain amino acids by digesting extracellular protein.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35726024/ · DOI 10.1038/s42255-022-00583-z","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"119e62f9-c127-5d08-8f3a-071034f89385","evidence_kind":"source_excerpt","locator":"Lines 258-264","start_line":258,"end_line":264,"excerpt":"## l-aspartate-protein-scavenging-rescue\nCells can obtain amino acids by digesting extracellular protein.\nBovine albumin supplementation restored aspartate and pyrimidine-related metabolites and partly rescued hypoxic growth in the tested KRAS-mutant human PDAC cultures.\nModel: Human MIA PaCa-2-centered hypoxic culture, albumin addition and macropinocytosis experiments.\nLimitations: This is an extracellular protein-scavenging mechanism, not evidence of direct intact dietary protein delivery to a tumor.\nEvidence access: Primary full text\nAdaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35726024/ · DOI 10.1038/s42255-022-00583-z","model_system":"Human MIA PaCa-2-centered hypoxic culture, albumin addition and macropinocytosis experiments.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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