{"id":"e30dad4e-4451-58cf-8f61-d7d9cc2e5d64","stable_key":"56f1d914-e7da-595a-af69-c217b2b47407:l-phenylalanine-inflammation-feedback","predicate":"is_downregulated_during","statement":"LPS at 1 microgram/mL reduced GFRP expression in human THP-1 cells; with interferon-gamma plus LPS, pteridine production became phenylalanine-independent.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ff5dee4f-5dbf-5a71-84d3-8bf46b395e2c","mechanism_event_label":"Inflammatory stimulation changed how this cell model responded to phenylalanine.","subject":{"id":"94bd66c9-b251-56b3-bc39-b0352d8871a4","slug":"gchfr","display_name":"Human GTP cyclohydrolase 1 feedback regulatory protein / GCHFR","entity_type_key":"protein"},"object":{"id":"67fad6b9-4211-5674-a5a0-c1ca18cab1f2","slug":"thp1-lps-pteridine-response","display_name":"THP-1 pteridine response under LPS and interferon-gamma","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ff5dee4f-5dbf-5a71-84d3-8bf46b395e2c","stable_key":"56f1d914-e7da-595a-af69-c217b2b47407:l-phenylalanine-inflammation-feedback-event","event_type":"observed_relationship","label":"Inflammatory stimulation changed how this cell model responded to phenylalanine.","description":"LPS at 1 microgram/mL reduced GFRP expression in human THP-1 cells; with interferon-gamma plus LPS, pteridine production became phenylalanine-independent.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"94bd66c9-b251-56b3-bc39-b0352d8871a4","slug":"gchfr","display_name":"Human GTP cyclohydrolase 1 feedback regulatory protein / GCHFR","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"67fad6b9-4211-5674-a5a0-c1ca18cab1f2","slug":"thp1-lps-pteridine-response","display_name":"THP-1 pteridine response under LPS and interferon-gamma","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":"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":""},{"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":4,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human THP-1 cells; interferon-gamma alone compared with interferon-gamma plus LPS.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Pteridine output is not synonymous with bioavailable BH4; no clinical inflammatory threshold is defined.","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":"Inflammatory stimulation changed how this cell model responded to phenylalanine.","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":"4bbb5b55-d3e5-5555-8880-b62bfb9925a8","evidence_kind":"source_excerpt","locator":"Lines 54-60","start_line":54,"end_line":60,"excerpt":"## l-phenylalanine-inflammation-feedback\nInflammatory stimulation changed how this cell model responded to phenylalanine.\nLPS at 1 microgram/mL reduced GFRP expression in human THP-1 cells; with interferon-gamma plus LPS, pteridine production became phenylalanine-independent.\nModel: Human THP-1 cells; interferon-gamma alone compared with interferon-gamma plus LPS.\nLimitations: Pteridine output is not synonymous with bioavailable BH4; no clinical inflammatory threshold is defined.\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":"Human THP-1 cells; interferon-gamma alone compared with interferon-gamma plus LPS.","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. Not publisher full text.","file_path":"","sha256":"4d53adcd4acc7a9aecf44ccb2623ec540c9d221a0f7c00002585870b39b8ffb8","revision_id":"fd182a81-4ab7-559a-9c77-fb4cf72982ef","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}