{"id":"d7bbe1fe-4503-5164-acfa-71914569b68a","stable_key":"dff9f743-3766-5f20-a71e-d6d2bd5bfb6f:va-cyp26a1-primary-hydroxylation","predicate":"produces","statement":"Recombinant human CYP26A1 hydroxylated all-trans-retinoic acid to 4-hydroxy-retinoic acid.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"ada15132-26c3-539e-9a1d-134fcd5902c6","mechanism_event_label":"This P450 begins oxidative removal of the signaling retinoid.","subject":{"id":"70c87719-ca79-54b6-af5e-c2e2e072ddd1","slug":"cyp26a1","display_name":"Cytochrome P450 26A1 / CYP26A1","entity_type_key":"protein"},"object":{"id":"a7751ca8-55d1-513a-958a-c9a887e67538","slug":"4-hydroxy-all-trans-retinoic-acid","display_name":"4-Hydroxy-all-trans-retinoic acid","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"ada15132-26c3-539e-9a1d-134fcd5902c6","stable_key":"dff9f743-3766-5f20-a71e-d6d2bd5bfb6f:va-cyp26a1-primary-hydroxylation-event","event_type":"biochemical_relationship","label":"This P450 begins oxidative removal of the signaling retinoid.","description":"Recombinant human CYP26A1 hydroxylated all-trans-retinoic acid to 4-hydroxy-retinoic acid.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"05487b29-8c59-5af8-83cf-cf9c79c5ecb8","slug":"all-trans-retinoic-acid","display_name":"All-trans-retinoic acid","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"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":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":"2e1f7e0a-8b54-5ea3-9d34-01e7167f9097","slug":"heme","display_name":"Heme","entity_type_key":"small_molecule"},"role":"prosthetic-group","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"70c87719-ca79-54b6-af5e-c2e2e072ddd1","slug":"cyp26a1","display_name":"Cytochrome P450 26A1 / CYP26A1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"a7751ca8-55d1-513a-958a-c9a887e67538","slug":"4-hydroxy-all-trans-retinoic-acid","display_name":"4-Hydroxy-all-trans-retinoic acid","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"NADPH and heme-containing P450 machinery support retinoid oxidation; nutritional deficiency was not tested.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human CYP26A1/CYP26B1 expressed in insect cells; purified/reconstituted metabolism and tissue assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"All-trans-retinoic-acid concentration series with P450 reductase and NADPH.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Assay kinetics are not whole-body clearance; hydroxylated products are not assumed biologically inert.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin A research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-a","display_name":"Vitamin A","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens recombinant protein in insect cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"outcome","value_text":"Recombinant human CYP26A1 hydroxylated all-trans-retinoic acid to 4-hydroxy-retinoic acid.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"This P450 begins oxidative removal of the signaling retinoid.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[va-topletz-2012] Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases (2012). https://pubmed.ncbi.nlm.nih.gov/22020119/ DOI: 10.1016/j.bcp.2011.10.007","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Reconstituted enzyme/microsomes","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"3bc81fdb-dfd6-5554-a8d2-ab05a74857f0","evidence_kind":"source_excerpt","locator":"Lines 601-614","start_line":601,"end_line":614,"excerpt":"### va-cyp26a1-primary-hydroxylation\nRecombinant human CYP26A1 hydroxylated all-trans-retinoic acid to 4-hydroxy-retinoic acid.\nCondition category: normal\nnutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This P450 begins oxidative removal of the signaling retinoid.\norganism: Homo sapiens recombinant protein in insect cells\ntissue_or_cell_type: Reconstituted enzyme/microsomes\nexperimental_model: Human CYP26A1/CYP26B1 expressed in insect cells; purified/reconstituted metabolism and tissue assays.\nlimitations: Assay kinetics are not whole-body clearance; hydroxylated products are not assumed biologically inert.\nexposure: All-trans-retinoic-acid concentration series with P450 reductase and NADPH.\noutcome: Recombinant human CYP26A1 hydroxylated all-trans-retinoic acid to 4-hydroxy-retinoic acid.\nevidence_location: Abstract\ncross_nutrient: NADPH and heme-containing P450 machinery support retinoid oxidation; nutritional deficiency was not tested.\n[va-topletz-2012] Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases (2012). https://pubmed.ncbi.nlm.nih.gov/22020119/ DOI: 10.1016/j.bcp.2011.10.007","model_system":"Human CYP26A1/CYP26B1 expressed in insect cells; 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Study references: [va-topletz-2012] Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases (2012). https://pubmed.ncbi.nlm.nih.gov/22020119/ DOI: 10.1016/j.bcp.2011.10.007","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"0c5474e2-be48-547b-b287-9c07a59c9ff1","stable_key":"import-dff9f743-3766-5f20-a71e-d6d2bd5bfb6f","title":"Vitamin A: forms, mechanisms, deficiency and excess (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":"b217224b262abbd77d6a0c8c9beefff9c022fae4d31e2a5273915d769b9a6546","revision_id":"61008909-871f-575c-b5e2-21542689ea3c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}