{"id":"34d53dec-633d-5a58-82a8-1d951418705e","stable_key":"56f1d914-e7da-595a-af69-c217b2b47407:l-phenylalanine-sapropterin-response","predicate":"reduces","statement":"In an 89-participant six-week PKU trial, sapropterin 10 mg/kg/day lowered mean phenylalanine by 236 micromol/L versus a 3 micromol/L rise with placebo; 44% versus 9% had at least a 30% reduction.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"b6247ceb-6db7-58be-beaf-f3c51ff31658","mechanism_event_label":"Providing the pharmaceutical cofactor helped some patients, with substantial response variation.","subject":{"id":"0ea697b5-afbd-5aa7-b916-99c33f7eaf30","slug":"sapropterin","display_name":"Sapropterin, pharmaceutical tetrahydrobiopterin","entity_type_key":"drug"},"object":{"id":"53c53d5a-5af6-5901-ba09-bccf1f416178","slug":"human-plasma-phenylalanine","display_name":"Human plasma phenylalanine concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"b6247ceb-6db7-58be-beaf-f3c51ff31658","stable_key":"56f1d914-e7da-595a-af69-c217b2b47407:l-phenylalanine-sapropterin-response-event","event_type":"observed_relationship","label":"Providing the pharmaceutical cofactor helped some patients, with substantial response variation.","description":"In an 89-participant six-week PKU trial, sapropterin 10 mg/kg/day lowered mean phenylalanine by 236 micromol/L versus a 3 micromol/L rise with placebo; 44% versus 9% had at least a 30% reduction.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"0ea697b5-afbd-5aa7-b916-99c33f7eaf30","slug":"sapropterin","display_name":"Sapropterin, pharmaceutical tetrahydrobiopterin","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"53c53d5a-5af6-5901-ba09-bccf1f416178","slug":"human-plasma-phenylalanine","display_name":"Human plasma phenylalanine concentration","entity_type_key":"cellular_process"},"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":"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":""},{"entity":{"id":"ea908671-6f85-5342-abe4-1a466a3b0572","slug":"pah","display_name":"Human phenylalanine hydroxylase / PAH","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Randomized human PKU study enriched through prior responsiveness assessment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Not all PAH defects respond; trial dose is historical evidence, not individualized guidance.","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":"Providing the pharmaceutical cofactor helped some patients, with substantial response variation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17693179/ · DOI 10.1016/S0140-6736(07)61234-3","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"8af06d8f-135e-57b8-972e-5594c7e1f7a6","evidence_kind":"source_excerpt","locator":"Lines 222-228","start_line":222,"end_line":228,"excerpt":"## l-phenylalanine-sapropterin-response\nProviding the pharmaceutical cofactor helped some patients, with substantial response variation.\nIn an 89-participant six-week PKU trial, sapropterin 10 mg/kg/day lowered mean phenylalanine by 236 micromol/L versus a 3 micromol/L rise with placebo; 44% versus 9% had at least a 30% reduction.\nModel: Randomized human PKU study enriched through prior responsiveness assessment.\nLimitations: Not all PAH defects respond; trial dose is historical evidence, not individualized guidance.\nEvidence access: Primary abstract\nEfficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17693179/ · DOI 10.1016/S0140-6736(07)61234-3","model_system":"Randomized human PKU study enriched through prior responsiveness assessment.","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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