{"id":"5d52185f-b643-5e88-a041-47f219b68a05","stable_key":"1deb434a-3547-51a0-a038-87b1ce79ec38:vd-act-cyp2r1-d3","predicate":"produces","statement":"Recombinant human CYP2R1 hydroxylated cholecalciferol at C25 to produce calcifediol.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"eff7628a-bae1-5b66-a066-8e56d6fdf8bd","mechanism_event_label":"CYP2R1 performs the first activation step for D3.","subject":{"id":"54fd3aae-6183-5f9a-827e-f4dd7683eea7","slug":"cyp2r1","display_name":"Human vitamin D 25-hydroxylase / CYP2R1","entity_type_key":"protein"},"object":{"id":"6bd73bd2-1f0a-5caa-ba69-7ce1b75364bb","slug":"calcifediol","display_name":"Calcifediol / 25-hydroxyvitamin D3","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"eff7628a-bae1-5b66-a066-8e56d6fdf8bd","stable_key":"1deb434a-3547-51a0-a038-87b1ce79ec38:vd-act-cyp2r1-d3-event","event_type":"biochemical_relationship","label":"CYP2R1 performs the first activation step for D3.","description":"Recombinant human CYP2R1 hydroxylated cholecalciferol at C25 to produce calcifediol.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"54fd3aae-6183-5f9a-827e-f4dd7683eea7","slug":"cyp2r1","display_name":"Human vitamin D 25-hydroxylase / CYP2R1","entity_type_key":"protein"},"role":"enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b162e431-b442-5400-9335-ec91f7875a4e","slug":"cholecalciferol","display_name":"Cholecalciferol","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6bd73bd2-1f0a-5caa-ba69-7ce1b75364bb","slug":"calcifediol","display_name":"Calcifediol / 25-hydroxyvitamin D3","entity_type_key":"small_molecule"},"role":"product","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Primary abstract, substrate product positions and kinetic comparison.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant human enzyme metabolism","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"D3 substrate series; reported Km 0.45 micromolar and kcat 0.97 per minute.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"In-vitro kinetics depend on assay setup and are not serum cutoffs.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient","value_text":"Vitamin D2 and D3","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-d","display_name":"Vitamin D2 and D3","entity_type_key":"chemical_species"}},{"dimension":"nutrient_topic","value_text":"Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-d","display_name":"Vitamin D2 and D3","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens protein","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"CYP2R1 performs the first activation step for D3.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[shinkyo2004] Metabolism of vitamin D by human microsomal CYP2R1. (2004). https://pubmed.ncbi.nlm.nih.gov/15465040/ DOI: 10.1016/j.bbrc.2004.09.073","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"microsomal enzyme preparation","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b8f324a2-d0be-5eda-9ca9-dfe59d793bc6","evidence_kind":"source_excerpt","locator":"Lines 287-300","start_line":287,"end_line":300,"excerpt":"### vd-act-cyp2r1-d3\nRecombinant human CYP2R1 hydroxylated cholecalciferol at C25 to produce calcifediol.\nCondition category: normal\nnutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: CYP2R1 performs the first activation step for D3.\norganism: Homo sapiens protein\ntissue_or_cell_type: microsomal enzyme preparation\nexperimental_model: Recombinant human enzyme metabolism\nlimitations: In-vitro kinetics depend on assay setup and are not serum cutoffs.\nexposure: D3 substrate series; reported Km 0.45 micromolar and kcat 0.97 per minute.\ncross_nutrient: false\nevidence_location: Primary abstract, substrate product positions and kinetic comparison.\nnutrient: Vitamin D2 and D3\n[shinkyo2004] Metabolism of vitamin D by human microsomal CYP2R1. 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