{"id":"dd76804b-3ca7-53b8-ac93-e338f64371db","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-reg-tet1-human-activity","predicate":"enhances-assayed-activity","statement":"Vitamin C increased hydroxymethylcytosine production by recombinant human TET1 catalytic domain in the reported pH 8.0 assay containing Fe(II) and 2-oxoglutarate. This demonstrates assay enhancement, without establishing obligatory ascorbate binding.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"cc1133f8-daa8-5d80-abe0-39d7176886e5","mechanism_event_label":"Vitamin C helped the isolated human enzyme modify DNA under these test conditions.","subject":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"object":{"id":"5fcc7eb2-480f-576e-9028-cb5f8f8a6d73","slug":"tet1","display_name":"TET1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"cc1133f8-daa8-5d80-abe0-39d7176886e5","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-reg-tet1-human-activity-event","event_type":"biochemical_relationship","label":"Vitamin C helped the isolated human enzyme modify DNA under these test conditions.","description":"Vitamin C increased hydroxymethylcytosine production by recombinant human TET1 catalytic domain in the reported pH 8.0 assay containing Fe(II) and 2-oxoglutarate. This demonstrates assay enhancement, without establishing obligatory ascorbate binding.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"da1a7137-08f2-5a36-8bb6-377fbd32e327","slug":"vitamin-c","display_name":"Vitamin C","entity_type_key":"chemical_species"},"role":"nutrient context","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"5fcc7eb2-480f-576e-9028-cb5f8f8a6d73","slug":"tet1","display_name":"TET1","entity_type_key":"protein"},"role":"enzyme","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"59d6d1cd-df32-5b58-b950-3188bc7b95d6","slug":"iron-ii","display_name":"Ferrous iron","entity_type_key":"ion"},"role":"metal cofactor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"628ddc2d-e4d9-59c7-ae76-0c0cab80a6b1","slug":"2-oxoglutarate","display_name":"2-Oxoglutarate","entity_type_key":"small_molecule"},"role":"cosubstrate","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"527d52ae-fa29-5d2e-990e-390943d4ebfb","slug":"dna-5-methylcytosine","display_name":"DNA 5-methylcytosine residues","entity_type_key":"chemical_species"},"role":"substrate modification","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"befcc80f-1af7-53f5-b162-4eefaafc4cf0","slug":"dna-5-hydroxymethylcytosine","display_name":"DNA 5-hydroxymethylcytosine residues","entity_type_key":"chemical_species"},"role":"product modification","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Figure 3a; Methods Tet activity assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified recombinant human TET1 catalytic-domain assay; antibody detection of hydroxymethylated biotinylated DNA","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"10 min at 37°C; 1.2 µg enzyme, 178.2 ng DNA, 3.7 µM ammonium iron(II) sulfate, 1 mM 2-oxoglutarate, titrated vitamin C (Sigma A5960).","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Purified-domain result; oxidation-prone buffer differs from cellular iron conditions. Exact plotted titration values not transcribed.","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 protein","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Vitamin C helped the isolated human enzyme modify DNA under these test conditions.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[c-reg-blaschke] Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23812591/ DOI: 10.1038/nature12362","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cell-free","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"d3c56e71-88a6-561d-9b28-120fa57ee7b0","evidence_kind":"source_excerpt","locator":"Lines 963-975","start_line":963,"end_line":975,"excerpt":"### c-reg-tet1-human-activity\nVitamin C increased hydroxymethylcytosine production by recombinant human TET1 catalytic domain in the reported pH 8.0 assay containing Fe(II) and 2-oxoglutarate. This demonstrates assay enhancement, without establishing obligatory ascorbate binding.\nCondition category: normal\nnutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Vitamin C helped the isolated human enzyme modify DNA under these test conditions.\norganism: Homo sapiens protein\ntissue_or_cell_type: Cell-free\nexperimental_model: Purified recombinant human TET1 catalytic-domain assay; antibody detection of hydroxymethylated biotinylated DNA\nlimitations: Purified-domain result; oxidation-prone buffer differs from cellular iron conditions. Exact plotted titration values not transcribed.\nexposure: 10 min at 37°C; 1.2 µg enzyme, 178.2 ng DNA, 3.7 µM ammonium iron(II) sulfate, 1 mM 2-oxoglutarate, titrated vitamin C (Sigma A5960).\ncross_nutrient: true\nevidence_location: Figure 3a; Methods Tet activity assay\n[c-reg-blaschke] Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23812591/ DOI: 10.1038/nature12362","model_system":"Purified recombinant human TET1 catalytic-domain assay; antibody detection of hydroxymethylated biotinylated DNA","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [c-reg-blaschke] Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23812591/ DOI: 10.1038/nature12362","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}