{"id":"36fdd20b-4387-5d15-9ea5-80c79b4a87ad","stable_key":"63ce713e-6aea-59f6-9896-ca30e010b2ce:l-tyrosine-th-cofactor-regulation","predicate":"binds","statement":"Recombinant human TH1 bound natural BH4 with negative cooperativity; Ser40 phosphorylation increased apparent BH4 affinity.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"0778cab5-f19c-5a77-8c1d-aacfa59c335b","mechanism_event_label":"The cofactor response changes with enzyme regulation.","subject":{"id":"1c231b90-c106-507a-8766-870ecb40e368","slug":"tetrahydrobiopterin","display_name":"Tetrahydrobiopterin / BH4","entity_type_key":"small_molecule"},"object":{"id":"e4e0f24b-1e70-573d-b719-039a90191b90","slug":"human-tyrosine-hydroxylase","display_name":"Human tyrosine hydroxylase","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"0778cab5-f19c-5a77-8c1d-aacfa59c335b","stable_key":"63ce713e-6aea-59f6-9896-ca30e010b2ce:l-tyrosine-th-cofactor-regulation-event","event_type":"observed_relationship","label":"The cofactor response changes with enzyme regulation.","description":"Recombinant human TH1 bound natural BH4 with negative cooperativity; Ser40 phosphorylation increased apparent BH4 affinity.","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":"e4e0f24b-1e70-573d-b719-039a90191b90","slug":"human-tyrosine-hydroxylase","display_name":"Human tyrosine hydroxylase","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"bcfef85f-831d-5439-ba51-1aef4b090441","slug":"l-tyrosine","display_name":"L-Tyrosine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"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":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human TH1 kinetics and surface plasmon resonance; PKA phosphorylation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"These kinetic values are not blood targets or instructions to supplement BH4.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-tyrosine","display_name":"L-Tyrosine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"The cofactor response changes with enzyme regulation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Tyrosine hydroxylase binds tetrahydrobiopterin cofactor with negative cooperativity, as shown by kinetic analyses and surface plasmon resonance detection. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10411647/ · DOI 10.1046/j.1432-1327.1999.00445.x","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"9edc559f-6f15-59ae-aae4-41e507b4455a","evidence_kind":"source_excerpt","locator":"Lines 28-34","start_line":28,"end_line":34,"excerpt":"## l-tyrosine-th-cofactor-regulation\nThe cofactor response changes with enzyme regulation.\nRecombinant human TH1 bound natural BH4 with negative cooperativity; Ser40 phosphorylation increased apparent BH4 affinity.\nModel: Human TH1 kinetics and surface plasmon resonance; PKA phosphorylation.\nLimitations: These kinetic values are not blood targets or instructions to supplement BH4.\nEvidence access: Primary abstract\nTyrosine hydroxylase binds tetrahydrobiopterin cofactor with negative cooperativity, as shown by kinetic analyses and surface plasmon resonance detection. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10411647/ · DOI 10.1046/j.1432-1327.1999.00445.x","model_system":"Human TH1 kinetics and surface plasmon resonance; PKA phosphorylation.","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":"12917df2-c6e0-5b61-850f-dbff6d4b4d30","stable_key":"import-63ce713e-6aea-59f6-9896-ca30e010b2ce","title":"L-Tyrosine: catecholamines, thyroid chemistry, pigment, 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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