{"id":"19b2ac9f-1eb4-5b21-9fcb-ba753c73248c","stable_key":"56f1d914-e7da-595a-af69-c217b2b47407:l-phenylalanine-gch1-feedforward","predicate":"stimulates_via_gchfr","statement":"Recombinant human GFRP enabled phenylalanine-dependent stimulation of recombinant human GCH1.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"fa3d1204-57f4-554c-97bf-645c071cf36d","mechanism_event_label":"The substrate can signal for more of the cofactor-making machinery to work.","subject":{"id":"190407ad-0219-54b5-b05f-7c75f3895ca6","slug":"l-phenylalanine","display_name":"L-Phenylalanine","entity_type_key":"small_molecule"},"object":{"id":"0a0535e5-9e65-5125-a31d-fcd0cd3e26df","slug":"gch1","display_name":"GCH1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"fa3d1204-57f4-554c-97bf-645c071cf36d","stable_key":"56f1d914-e7da-595a-af69-c217b2b47407:l-phenylalanine-gch1-feedforward-event","event_type":"observed_relationship","label":"The substrate can signal for more of the cofactor-making machinery to work.","description":"Recombinant human GFRP enabled phenylalanine-dependent stimulation of recombinant human GCH1.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"190407ad-0219-54b5-b05f-7c75f3895ca6","slug":"l-phenylalanine","display_name":"L-Phenylalanine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0a0535e5-9e65-5125-a31d-fcd0cd3e26df","slug":"gch1","display_name":"GCH1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"94bd66c9-b251-56b3-bc39-b0352d8871a4","slug":"gchfr","display_name":"Human GTP cyclohydrolase 1 feedback regulatory protein / GCHFR","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"1c231b90-c106-507a-8766-870ecb40e368","slug":"tetrahydrobiopterin","display_name":"Tetrahydrobiopterin / BH4","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant human proteins; primary abstract.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"GCH1 controls an early BH4-biosynthesis step; this is not proof that supplemental phenylalanine raises BH4 in every tissue.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Phenylalanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-phenylalanine","display_name":"L-Phenylalanine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"The substrate can signal for more of the cofactor-making machinery to work.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Bacterial lipopolysaccharide down-regulates expression of GTP cyclohydrolase I feedback regulatory protein. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11799107/ · DOI 10.1074/jbc.M107326200","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"468850a0-c649-59ef-9a8b-2f58364b84ec","evidence_kind":"source_excerpt","locator":"Lines 38-44","start_line":38,"end_line":44,"excerpt":"## l-phenylalanine-gch1-feedforward\nThe substrate can signal for more of the cofactor-making machinery to work.\nRecombinant human GFRP enabled phenylalanine-dependent stimulation of recombinant human GCH1.\nModel: Recombinant human proteins; primary abstract.\nLimitations: GCH1 controls an early BH4-biosynthesis step; this is not proof that supplemental phenylalanine raises BH4 in every tissue.\nEvidence access: Primary abstract\nBacterial lipopolysaccharide down-regulates expression of GTP cyclohydrolase I feedback regulatory protein. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11799107/ · DOI 10.1074/jbc.M107326200","model_system":"Recombinant human proteins; primary abstract.","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":"54de7c56-1e60-5d7b-8ef9-852c58ae92ba","stable_key":"import-56f1d914-e7da-595a-af69-c217b2b47407","title":"L-Phenylalanine: transport, protein synthesis, cofactor recycling 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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