{"id":"24ff3c04-0c7c-5660-8a65-490f1efa9b54","stable_key":"1deb434a-3547-51a0-a038-87b1ce79ec38:vd-act-por-support","predicate":"supports_catalysis","statement":"Human POR supported CYP2R1-mediated cholecalciferol 25-hydroxylation, with maximal measured activity near a 4:1 POR:CYP2R1 molar ratio.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"0a5ed1d5-2bf7-5be7-a366-7f3edf82dcd2","mechanism_event_label":"CYP2R1 needs an electron-supplying partner.","subject":{"id":"9a730557-ae90-5bf9-a716-c13a6ceef49b","slug":"por","display_name":"NADPH-cytochrome P450 oxidoreductase / POR","entity_type_key":"protein"},"object":{"id":"54fd3aae-6183-5f9a-827e-f4dd7683eea7","slug":"cyp2r1","display_name":"Human vitamin D 25-hydroxylase / CYP2R1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"0a5ed1d5-2bf7-5be7-a366-7f3edf82dcd2","stable_key":"1deb434a-3547-51a0-a038-87b1ce79ec38:vd-act-por-support-event","event_type":"biochemical_relationship","label":"CYP2R1 needs an electron-supplying partner.","description":"Human POR supported CYP2R1-mediated cholecalciferol 25-hydroxylation, with maximal measured activity near a 4:1 POR:CYP2R1 molar ratio.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9a730557-ae90-5bf9-a716-c13a6ceef49b","slug":"por","display_name":"NADPH-cytochrome P450 oxidoreductase / POR","entity_type_key":"protein"},"role":"electron_transfer_partner","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"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":1,"notes":""},{"entity":{"id":"4aba2a5e-8d06-5304-bb01-c0402b225a94","slug":"nadph","display_name":"NADPH","entity_type_key":"small_molecule"},"role":"electron_source","stoichiometry":null,"state_label":"","sequence_order":2,"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":3,"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":4,"notes":""},{"entity":{"id":"e2cd7179-f218-54e8-9ce9-7a836ae35fac","slug":"fad","display_name":"FAD","entity_type_key":"small_molecule"},"role":"por_cofactor","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"d3eacf85-1a35-546d-bd30-161474dd9691","slug":"fmn","display_name":"Flavin mononucleotide","entity_type_key":"small_molecule"},"role":"por_cofactor","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":"Primary Figure 2C; Methods 2.3 and reconstitution assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified enzyme and phospholipid-vesicle reconstitution","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"0.25 micromolar CYP2R1; varied POR; 30 min at 37 C; Figure 2C.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Assay optimum is not a tissue expression target or a vitamin dosing requirement.","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 proteins","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"CYP2R1 needs an electron-supplying partner.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[cheng2018] Properties of purified CYP2R1 in a reconstituted membrane environment and its 25-hydroxylation of 20-hydroxyvitamin D3. (2018). https://pubmed.ncbi.nlm.nih.gov/28716760/ DOI: 10.1016/j.jsbmb.2017.07.011","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"reconstituted membrane","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"d4b3ede8-f16a-5daa-abb8-7113e8fb2080","evidence_kind":"source_excerpt","locator":"Lines 392-405","start_line":392,"end_line":405,"excerpt":"### vd-act-por-support\nHuman POR supported CYP2R1-mediated cholecalciferol 25-hydroxylation, with maximal measured activity near a 4:1 POR:CYP2R1 molar ratio.\nCondition category: normal\nnutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: CYP2R1 needs an electron-supplying partner.\norganism: Homo sapiens proteins\ntissue_or_cell_type: reconstituted membrane\nexperimental_model: Purified enzyme and phospholipid-vesicle reconstitution\nlimitations: Assay optimum is not a tissue expression target or a vitamin dosing requirement.\nexposure: 0.25 micromolar CYP2R1; varied POR; 30 min at 37 C; Figure 2C.\ncross_nutrient: true\nevidence_location: Primary Figure 2C; Methods 2.3 and reconstitution assays.\nnutrient: Vitamin D2 and D3\n[cheng2018] Properties of purified CYP2R1 in a reconstituted membrane environment and its 25-hydroxylation of 20-hydroxyvitamin D3. 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