{"id":"2ab3a3c1-28ec-59e7-993c-1fd32a27307e","stable_key":"1deb434a-3547-51a0-a038-87b1ce79ec38:vd-act-fdx1-cyp27b1","predicate":"supports_catalysis","statement":"Human adrenodoxin supported CYP27B1 activity in reconstituted vesicles; varying adrenodoxin changed apparent kinetic parameters for calcifediol hydroxylation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"ed9af8a8-b6c6-54ab-8328-7f7306591a46","mechanism_event_label":"An iron-sulfur electron carrier supports the final D3 activation step.","subject":{"id":"34590b7b-744d-5654-8b8c-8dc447c667bf","slug":"fdx1","display_name":"Human adrenodoxin / FDX1","entity_type_key":"protein"},"object":{"id":"a1d0238c-7529-5175-b5f9-71dc9bc61ed5","slug":"cyp27b1","display_name":"Vitamin D 1-alpha-hydroxylase / CYP27B1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"ed9af8a8-b6c6-54ab-8328-7f7306591a46","stable_key":"1deb434a-3547-51a0-a038-87b1ce79ec38:vd-act-fdx1-cyp27b1-event","event_type":"biochemical_relationship","label":"An iron-sulfur electron carrier supports the final D3 activation step.","description":"Human adrenodoxin supported CYP27B1 activity in reconstituted vesicles; varying adrenodoxin changed apparent kinetic parameters for calcifediol hydroxylation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"34590b7b-744d-5654-8b8c-8dc447c667bf","slug":"fdx1","display_name":"Human adrenodoxin / FDX1","entity_type_key":"protein"},"role":"electron_transfer_partner","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"02107865-f169-5624-9ea4-9448a4cce185","slug":"iron-sulfur-2fe2s","display_name":"[2Fe-2S] iron-sulfur cluster","entity_type_key":"chemical_species"},"role":"fdx1_redox_cluster","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"57304e14-8bdf-5490-a897-058461023f2e","slug":"fdxr","display_name":"Human ferredoxin reductase / FDXR","entity_type_key":"protein"},"role":"reductase","stoichiometry":null,"state_label":"","sequence_order":2,"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":3,"notes":""},{"entity":{"id":"a1d0238c-7529-5175-b5f9-71dc9bc61ed5","slug":"cyp27b1","display_name":"Vitamin D 1-alpha-hydroxylase / CYP27B1","entity_type_key":"protein"},"role":"enzyme","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"6bd73bd2-1f0a-5caa-ba69-7ce1b75364bb","slug":"calcifediol","display_name":"Calcifediol / 25-hydroxyvitamin D3","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"f5156c24-108f-5746-b114-ed764e79a3f4","slug":"calcitriol","display_name":"Calcitriol","entity_type_key":"small_molecule"},"role":"product","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 Tables 3-5, Figure 6A and Experimental procedures; full text retrieved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human CYP27B1/FDX1/FDXR kinetic reconstitution","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"FDX1 1-30 micromolar; 2-min incubations with calcifediol; Table 4.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The experiment varies intact FDX1, not dietary iron. Reciprocal changes of apparent Km and turnover prevent interpreting FDX1 level as a universal limiting factor.","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":"An iron-sulfur electron carrier supports the final D3 activation step.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[tang2012] Expression of human CYP27B1 in Escherichia coli and characterization in phospholipid vesicles. (2012). https://pubmed.ncbi.nlm.nih.gov/22862690/ DOI: 10.1111/j.1742-4658.2012.08736.x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"reconstituted mitochondrial membrane","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"a17d91f9-588a-5aa8-aded-f6731cafde44","evidence_kind":"source_excerpt","locator":"Lines 452-465","start_line":452,"end_line":465,"excerpt":"### vd-act-fdx1-cyp27b1\nHuman adrenodoxin supported CYP27B1 activity in reconstituted vesicles; varying adrenodoxin changed apparent kinetic parameters for calcifediol hydroxylation.\nCondition category: normal\nnutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: An iron-sulfur electron carrier supports the final D3 activation step.\norganism: Homo sapiens proteins\ntissue_or_cell_type: reconstituted mitochondrial membrane\nexperimental_model: Human CYP27B1/FDX1/FDXR kinetic reconstitution\nlimitations: The experiment varies intact FDX1, not dietary iron. Reciprocal changes of apparent Km and turnover prevent interpreting FDX1 level as a universal limiting factor.\nexposure: FDX1 1-30 micromolar; 2-min incubations with calcifediol; Table 4.\ncross_nutrient: true\nevidence_location: Primary Tables 3-5, Figure 6A and Experimental procedures; full text retrieved.\nnutrient: Vitamin D2 and D3\n[tang2012] Expression of human CYP27B1 in Escherichia coli and characterization in phospholipid vesicles. (2012). https://pubmed.ncbi.nlm.nih.gov/22862690/ DOI: 10.1111/j.1742-4658.2012.08736.x","model_system":"Human CYP27B1/FDX1/FDXR kinetic reconstitution","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [tang2012] Expression of human CYP27B1 in Escherichia coli and characterization in phospholipid vesicles. (2012). https://pubmed.ncbi.nlm.nih.gov/22862690/ DOI: 10.1111/j.1742-4658.2012.08736.x","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c95c763c-5b31-5b3f-a2f8-2dfe5ef0d3ca","stable_key":"import-1deb434a-3547-51a0-a038-87b1ce79ec38","title":"Vitamin D2 and D3: 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":"51004bf0d78db6146b8f198b0688a3cc7d4ea9822415a9c034f4c8790fb4e38b","revision_id":"d52ff207-a311-5f24-96f4-462838792db5","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}