{"id":"7f47146e-f071-5426-851a-5213d64dc08a","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:vc-enzyme-sepiapterin-co-response","predicate":"augments-with-ascorbate","statement":"Sepiapterin increased norepinephrine content in SH-SY5Y cultures and 50 micromolar ascorbate increased the response further after 24 hours.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"9506d14d-b2fc-51b8-a5c4-a1831058f676","mechanism_event_label":"Supporting a second cofactor pathway enhanced the neuronal response to vitamin C.","subject":{"id":"3a0d87b3-2fc9-5ba4-a242-9cb9dcde4a3f","slug":"sepiapterin","display_name":"Sepiapterin","entity_type_key":"small_molecule"},"object":{"id":"34ab29ee-eb2b-5e51-9d25-0c1f8d5b97d9","slug":"norepinephrine","display_name":"Norepinephrine","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"9506d14d-b2fc-51b8-a5c4-a1831058f676","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:vc-enzyme-sepiapterin-co-response-event","event_type":"biochemical_relationship","label":"Supporting a second cofactor pathway enhanced the neuronal response to vitamin C.","description":"Sepiapterin increased norepinephrine content in SH-SY5Y cultures and 50 micromolar ascorbate increased the response further after 24 hours.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3a0d87b3-2fc9-5ba4-a242-9cb9dcde4a3f","slug":"sepiapterin","display_name":"Sepiapterin","entity_type_key":"small_molecule"},"role":"BH4-salvage-precursor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"role":"supporting-reductant","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e4e0f24b-1e70-573d-b719-039a90191b90","slug":"human-tyrosine-hydroxylase","display_name":"Human tyrosine hydroxylase","entity_type_key":"protein"},"role":"cofactor-dependent-enzyme","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"34ab29ee-eb2b-5e51-9d25-0c1f8d5b97d9","slug":"norepinephrine","display_name":"Norepinephrine","entity_type_key":"small_molecule"},"role":"readout","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Ascorbate interacts with the pterin cofactor pathway supporting amino-acid-derived catecholamine synthesis; sepiapterin is kept distinct from BH4.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human SH-SY5Y neuroblastoma cultures","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Sepiapterin dose series with or without 50 micromolar ascorbate, 24 hours; Fig.3C.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Fig.3C tests sepiapterin, not direct BH4 dosing; BH4 recycling by ascorbate is an interpretation rather than a measured reaction in this experiment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin C research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-c","display_name":"Vitamin C","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Supporting a second cofactor pathway enhanced the neuronal response to vitamin C.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[may2012] Mechanisms of ascorbic acid stimulation of norepinephrine synthesis in neuronal cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22925890/ DOI: 10.1016/j.bbrc.2012.08.054","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Neuronal tumor cell line","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"7a079d76-764e-52dd-a439-96e5609c1354","evidence_kind":"source_excerpt","locator":"Lines 846-857","start_line":846,"end_line":857,"excerpt":"### vc-enzyme-sepiapterin-co-response\nSepiapterin increased norepinephrine content in SH-SY5Y cultures and 50 micromolar ascorbate increased the response further after 24 hours.\nCondition category: normal\nnutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Supporting a second cofactor pathway enhanced the neuronal response to vitamin C.\norganism: Homo sapiens\ntissue_or_cell_type: Neuronal tumor cell line\nexperimental_model: Human SH-SY5Y neuroblastoma cultures\nlimitations: Fig.3C tests sepiapterin, not direct BH4 dosing; BH4 recycling by ascorbate is an interpretation rather than a measured reaction in this experiment.\ncross_nutrient: Ascorbate interacts with the pterin cofactor pathway supporting amino-acid-derived catecholamine synthesis; sepiapterin is kept distinct from BH4.\nexposure: Sepiapterin dose series with or without 50 micromolar ascorbate, 24 hours; Fig.3C.\n[may2012] Mechanisms of ascorbic acid stimulation of norepinephrine synthesis in neuronal cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22925890/ DOI: 10.1016/j.bbrc.2012.08.054","model_system":"Human SH-SY5Y neuroblastoma cultures","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [may2012] Mechanisms of ascorbic acid stimulation of norepinephrine synthesis in neuronal cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22925890/ DOI: 10.1016/j.bbrc.2012.08.054","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"fa811221-13bd-5c10-adc1-eaf097c7703c","stable_key":"import-cb568d28-484a-5c2e-9fcc-2d780358e514","title":"Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"b7fd83f956abb81855f2ea23199ba14e465cd91f4a2ac560277ec21ddafd7bfc","revision_id":"6cde9bbb-d712-5746-82a6-85b144253efa","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}