{"id":"34182ca1-8599-53a4-8a19-872c27f7d4b4","stable_key":"6612c190-1948-5bcf-bbe3-a7f6c50fa3cf:l-proline-tgfb-proline","predicate":"consumes_reducing_power_during","statement":"TGF-beta induced glutamine-derived proline synthesis in a Smad4-dependent fibroblast program; manipulations of mitochondrial redox potential or ATP production changed that synthesis.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"6b3f43ce-1bee-5e67-b338-50329dd6f9ee","mechanism_event_label":"Activated matrix-producing cells can use proline synthesis to handle metabolic demand.","subject":{"id":"d85b04b8-0244-577b-a664-03dbb52ae2fb","slug":"mouse-tgfb-proline-biosynthesis","display_name":"TGF-beta-stimulated proline synthesis in mouse fibroblasts","entity_type_key":"cellular_process"},"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":"6b3f43ce-1bee-5e67-b338-50329dd6f9ee","stable_key":"6612c190-1948-5bcf-bbe3-a7f6c50fa3cf:l-proline-tgfb-proline-event","event_type":"observed_relationship","label":"Activated matrix-producing cells can use proline synthesis to handle metabolic demand.","description":"TGF-beta induced glutamine-derived proline synthesis in a Smad4-dependent fibroblast program; manipulations of mitochondrial redox potential or ATP production changed that synthesis.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d85b04b8-0244-577b-a664-03dbb52ae2fb","slug":"mouse-tgfb-proline-biosynthesis","display_name":"TGF-beta-stimulated proline synthesis in mouse fibroblasts","entity_type_key":"cellular_process"},"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":"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":2,"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":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":"4aba2a5e-8d06-5304-bb01-c0402b225a94","slug":"nadph","display_name":"NADPH","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":"TGF-beta-stimulated fibroblast experiments; primary abstract, with mouse NIH3T3 model identified in the primary study.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"No dietary dose or general antifibrotic benefit 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":"Activated matrix-producing cells can use proline synthesis to handle metabolic demand.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Proline biosynthesis is a vent for TGFβ-induced mitochondrial redox stress. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32134147/ · DOI 10.15252/embj.2019103334","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"064ed638-e0a3-5731-a482-1229c5110787","evidence_kind":"source_excerpt","locator":"Lines 366-372","start_line":366,"end_line":372,"excerpt":"## l-proline-tgfb-proline\nActivated matrix-producing cells can use proline synthesis to handle metabolic demand.\nTGF-beta induced glutamine-derived proline synthesis in a Smad4-dependent fibroblast program; manipulations of mitochondrial redox potential or ATP production changed that synthesis.\nModel: TGF-beta-stimulated fibroblast experiments; primary abstract, with mouse NIH3T3 model identified in the primary study.\nLimitations: No dietary dose or general antifibrotic benefit is inferred.\nEvidence access: Primary abstract\nProline biosynthesis is a vent for TGFβ-induced mitochondrial redox stress. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32134147/ · DOI 10.15252/embj.2019103334","model_system":"TGF-beta-stimulated fibroblast experiments; primary abstract, with mouse NIH3T3 model identified in the primary study.","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; primary references, access levels and experimental limitations individually identified. 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