{"id":"7718b8c6-8048-5b10-aa77-484a3344aa31","stable_key":"6612c190-1948-5bcf-bbe3-a7f6c50fa3cf:l-proline-precursor-routing","predicate":"contributes_carbon_via_pycr3_to","statement":"Isotope tracing with gene silencing linked glutamine/glutamate-derived proline mainly to PYCR1/PYCR2 and ornithine-derived proline mainly to PYCRL in human melanoma cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"f93003ea-49cf-577b-8040-e199b8ea369e","mechanism_event_label":"Two precursor routes can feed the same product through differently placed enzymes.","subject":{"id":"c715e48e-42db-5fac-b4a4-c1285a68d085","slug":"ornithine","display_name":"L-Ornithine","entity_type_key":"small_molecule"},"object":{"id":"70ccd53c-83ad-5251-a4f5-6370973bc40a","slug":"l-proline","display_name":"L-Proline","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"f93003ea-49cf-577b-8040-e199b8ea369e","stable_key":"6612c190-1948-5bcf-bbe3-a7f6c50fa3cf:l-proline-precursor-routing-event","event_type":"observed_relationship","label":"Two precursor routes can feed the same product through differently placed enzymes.","description":"Isotope tracing with gene silencing linked glutamine/glutamate-derived proline mainly to PYCR1/PYCR2 and ornithine-derived proline mainly to PYCRL in human melanoma cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c715e48e-42db-5fac-b4a4-c1285a68d085","slug":"ornithine","display_name":"L-Ornithine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"70ccd53c-83ad-5251-a4f5-6370973bc40a","slug":"l-proline","display_name":"L-Proline","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7da684a4-2641-5bc6-93ae-8c6aa384e487","slug":"glutamate","display_name":"L-Glutamate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"8637bb39-2c30-5168-baaf-3e613d831db0","slug":"glutamine","display_name":"L-Glutamine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"ddcb770b-d815-5f25-b055-f1f15174140e","slug":"oat","display_name":"Human ornithine aminotransferase / OAT","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"6a5e6627-f4fd-5a02-b74b-371b629b076b","slug":"pycr1","display_name":"Human pyrroline-5-carboxylate reductase 1 / PYCR1","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"1efec84e-42f6-51db-9041-6b35fc092e3d","slug":"pycr2","display_name":"Human pyrroline-5-carboxylate reductase 2 / PYCR2","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""},{"entity":{"id":"6f3233f1-60ce-5c1d-ac42-394ceae60c5e","slug":"pycr3","display_name":"Human pyrroline-5-carboxylate reductase 3 / PYCR3 / PYCRL","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":7,"notes":""},{"entity":{"id":"cbf8b66e-3d66-53f0-9c21-bc9c014131e7","slug":"pyrroline-5-carboxylate","display_name":"Delta-1-pyrroline-5-carboxylate / P5C","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":8,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Lu1205 cells; 1 mM labeled precursors for eight hours; ornithine labeling required omission of extracellular proline.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The ornithine experiment used conditions the authors regarded as likely nonphysiological; no universal exclusive routing rule is inferred.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-proline","display_name":"L-Proline","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Two precursor routes can feed the same product through differently placed enzymes.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Functional specialization in proline biosynthesis of melanoma. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23024808/ · DOI 10.1371/journal.pone.0045190","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"17f551f5-e5dd-5cc3-8b85-1d5dd068993d","evidence_kind":"source_excerpt","locator":"Lines 38-44","start_line":38,"end_line":44,"excerpt":"## l-proline-precursor-routing\nTwo precursor routes can feed the same product through differently placed enzymes.\nIsotope tracing with gene silencing linked glutamine/glutamate-derived proline mainly to PYCR1/PYCR2 and ornithine-derived proline mainly to PYCRL in human melanoma cells.\nModel: Lu1205 cells; 1 mM labeled precursors for eight hours; ornithine labeling required omission of extracellular proline.\nLimitations: The ornithine experiment used conditions the authors regarded as likely nonphysiological; no universal exclusive routing rule is inferred.\nEvidence access: Primary full text\nFunctional specialization in proline biosynthesis of melanoma. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23024808/ · DOI 10.1371/journal.pone.0045190","model_system":"Lu1205 cells; 1 mM labeled precursors for eight hours; ornithine labeling required omission of extracellular proline.","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":"e5aa7fc5-ee52-5376-8169-416082a89fd1","stable_key":"import-6612c190-1948-5bcf-bbe3-a7f6c50fa3cf","title":"L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; 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