{"id":"e55caac4-f8ea-5083-8a58-de9cf043c806","stable_key":"3279ff78-2460-5064-bfc0-3f2987af85a0:melatonin-tph1-bh4","predicate":"supports_catalysis_by","statement":"Human pineal TPH activity was measured with BH4, and a transient 4alpha-hydroxytetrahydrobiopterin intermediate was detected.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"c629f339-8386-53f8-bb71-5d450d5dd165","mechanism_event_label":"The pterin cofactor participates chemically; it is not interchangeable with folate.","subject":{"id":"1c231b90-c106-507a-8766-870ecb40e368","slug":"tetrahydrobiopterin","display_name":"Tetrahydrobiopterin / BH4","entity_type_key":"small_molecule"},"object":{"id":"52d66ced-4bbe-567f-a641-b72b2c038b93","slug":"tph1","display_name":"Human tryptophan hydroxylase 1 / TPH1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"c629f339-8386-53f8-bb71-5d450d5dd165","stable_key":"3279ff78-2460-5064-bfc0-3f2987af85a0:melatonin-tph1-bh4-event","event_type":"biochemical_relationship","label":"The pterin cofactor participates chemically; it is not interchangeable with folate.","description":"Human pineal TPH activity was measured with BH4, and a transient 4alpha-hydroxytetrahydrobiopterin intermediate was detected.","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":"52d66ced-4bbe-567f-a641-b72b2c038b93","slug":"tph1","display_name":"Human tryptophan hydroxylase 1 / TPH1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/melatonin-research/10525150.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f\", \"start_char\": 0, \"end_char\": 1489, \"text_sha256\": \"032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant enzyme purification and catalysis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"L-tryptophan with tetrahydrobiopterin; purified tetrameric enzyme","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"TPH1 and neuronal TPH2 are distinct. A cofactor-dependent reaction does not prove supplemental cofactor increases melatonin in a replete person.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Melatonin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"melatonin","display_name":"Melatonin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human pineal TPH1 expressed in E. coli","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The pterin cofactor participates chemically; it is not interchangeable with folate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[melatonin-p10525150] Cloning and expression of recombinant human pineal tryptophan hydroxylase in Escherichia coli: purification and characterization of the cloned enzyme. (1999). https://pubmed.ncbi.nlm.nih.gov/10525150/ DOI: 10.1016/s0167-4838(99)00184-3","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Tryptophan hydroxylation","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"2715141d-d53d-54ad-a1a1-dc1ba89385dc","evidence_kind":"source_excerpt","locator":"Lines 149-160","start_line":149,"end_line":160,"excerpt":"### melatonin-tph1-bh4\nHuman pineal TPH activity was measured with BH4, and a transient 4alpha-hydroxytetrahydrobiopterin intermediate was detected.\nCondition category: normal\nnutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The pterin cofactor participates chemically; it is not interchangeable with folate.\norganism: Human pineal TPH1 expressed in E. coli\ntissue_or_cell_type: Tryptophan hydroxylation\nexperimental_model: Recombinant enzyme purification and catalysis\nlimitations: TPH1 and neuronal TPH2 are distinct. A cofactor-dependent reaction does not prove supplemental cofactor increases melatonin in a replete person.\nexposure: L-tryptophan with tetrahydrobiopterin; purified tetrameric enzyme\nevidence_span: {\"source_cache\": \"artifacts/melatonin-research/10525150.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f\", \"start_char\": 0, \"end_char\": 1489, \"text_sha256\": \"032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f\"}\n[melatonin-p10525150] Cloning and expression of recombinant human pineal tryptophan hydroxylase in Escherichia coli: purification and characterization of the cloned enzyme. 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