{"id":"376c40f1-0af7-54e7-8fac-5fe4e5c80db9","stable_key":"56f1d914-e7da-595a-af69-c217b2b47407:l-phenylalanine-gch1-feedback","predicate":"inhibits_gch1_through","statement":"BH4 and phenylalanine favored inhibited and activated human GCH1-GFRP complexes, respectively; ligand-dependent conformational changes stabilized binding.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"27692610-823c-55df-8b7a-f7b9472fbbfb","mechanism_event_label":"Cofactor production has both a demand signal and a feedback brake.","subject":{"id":"1c231b90-c106-507a-8766-870ecb40e368","slug":"tetrahydrobiopterin","display_name":"Tetrahydrobiopterin / BH4","entity_type_key":"small_molecule"},"object":{"id":"94bd66c9-b251-56b3-bc39-b0352d8871a4","slug":"gchfr","display_name":"Human GTP cyclohydrolase 1 feedback regulatory protein / GCHFR","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"27692610-823c-55df-8b7a-f7b9472fbbfb","stable_key":"56f1d914-e7da-595a-af69-c217b2b47407:l-phenylalanine-gch1-feedback-event","event_type":"observed_relationship","label":"Cofactor production has both a demand signal and a feedback brake.","description":"BH4 and phenylalanine favored inhibited and activated human GCH1-GFRP complexes, respectively; ligand-dependent conformational changes stabilized binding.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"1c231b90-c106-507a-8766-870ecb40e368","slug":"tetrahydrobiopterin","display_name":"Tetrahydrobiopterin / BH4","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"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":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"190407ad-0219-54b5-b05f-7c75f3895ca6","slug":"l-phenylalanine","display_name":"L-Phenylalanine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"0a0535e5-9e65-5125-a31d-fcd0cd3e26df","slug":"gch1","display_name":"GCH1","entity_type_key":"protein"},"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":"Human purified proteins, crystallography and binding/kinetic studies.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cofactor synthesis has additional steps; structural regulation does not establish a clinical depletion or supplementation effect.","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":"Cofactor production has both a demand signal and a feedback brake.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Biophysical and structural investigation of the regulation of human GTP cyclohydrolase I by its regulatory protein GFRP. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33387654/ · DOI 10.1016/j.jsb.2020.107691","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"c6ef3ac2-48d4-5980-a34c-e55ddd07efef","evidence_kind":"source_excerpt","locator":"Lines 46-52","start_line":46,"end_line":52,"excerpt":"## l-phenylalanine-gch1-feedback\nCofactor production has both a demand signal and a feedback brake.\nBH4 and phenylalanine favored inhibited and activated human GCH1-GFRP complexes, respectively; ligand-dependent conformational changes stabilized binding.\nModel: Human purified proteins, crystallography and binding/kinetic studies.\nLimitations: Cofactor synthesis has additional steps; structural regulation does not establish a clinical depletion or supplementation effect.\nEvidence access: Primary abstract\nBiophysical and structural investigation of the regulation of human GTP cyclohydrolase I by its regulatory protein GFRP. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33387654/ · DOI 10.1016/j.jsb.2020.107691","model_system":"Human purified proteins, crystallography and binding/kinetic studies.","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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