{"id":"1dfa03af-2812-5d93-9039-47504715f102","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-iron-ferric-reduction-uptake","predicate":"supports_ferric_reduction_for_cellular_iron_acquisition","statement":"Ascorbate enhanced ferric-NTA iron uptake; ascorbate oxidase and Fe(II) chelators inhibited the enhancement, supporting a required Fe(III)-to-Fe(II) reduction step in this cell model.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"5455c14c-1e63-50b0-af39-18eb7d941e24","mechanism_event_label":"Changing iron’s chemical state helped the intestinal-model cells acquire it.","subject":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"object":{"id":"c8904c5c-4a1a-5a61-be6b-63af25ff3ce9","slug":"caco2-apical-iron-uptake","display_name":"Caco-2 apical iron uptake","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"5455c14c-1e63-50b0-af39-18eb7d941e24","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-iron-ferric-reduction-uptake-event","event_type":"biochemical_relationship","label":"Changing iron’s chemical state helped the intestinal-model cells acquire it.","description":"Ascorbate enhanced ferric-NTA iron uptake; ascorbate oxidase and Fe(II) chelators inhibited the enhancement, supporting a required Fe(III)-to-Fe(II) reduction step in this cell model.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"964be7ac-43bd-5f3e-8326-94f0590de67a","slug":"iron-iii","display_name":"Ferric iron","entity_type_key":"ion"},"role":"starting_oxidation_state","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"59d6d1cd-df32-5b58-b950-3188bc7b95d6","slug":"iron-ii","display_name":"Ferrous iron","entity_type_key":"ion"},"role":"required_reduced_oxidation_state","stoichiometry":null,"state_label":"","sequence_order":1,"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":2,"notes":""},{"entity":{"id":"c8904c5c-4a1a-5a61-be6b-63af25ff3ce9","slug":"caco2-apical-iron-uptake","display_name":"Caco-2 apical iron uptake","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Vitamin C changes availability of iron for uptake; not proof that all iron absorption requires added vitamin C.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Differentiated human Caco-2 monolayers; apical ferric nitrilotriacetate and transepithelial transport assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Apical 10 micromolar Fe(III) as 1 Fe:2 NTA, varied ascorbic acid, ascorbate oxidase and Fe(II) chelators.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Chelator/oxidase interventions support redox dependence; the experiment does not identify every human intestinal transport step.","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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Changing iron’s chemical state helped the intestinal-model cells acquire it.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[c-han1995] Reduction of Fe(III) is required for uptake of nonheme iron by Caco-2 cells (1995). https://pubmed.ncbi.nlm.nih.gov/7738689/ DOI: 10.1093/jn/125.5.1291","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Human Caco-2 apical cell surface and culture medium","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"d26dfe51-f5a4-5650-a0b5-9764fafb3c19","evidence_kind":"source_excerpt","locator":"Lines 1554-1565","start_line":1554,"end_line":1565,"excerpt":"### c-iron-ferric-reduction-uptake\nAscorbate enhanced ferric-NTA iron uptake; ascorbate oxidase and Fe(II) chelators inhibited the enhancement, supporting a required Fe(III)-to-Fe(II) reduction step in this cell model.\nCondition category: normal\nnutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Changing iron’s chemical state helped the intestinal-model cells acquire it.\norganism: Homo sapiens\ntissue_or_cell_type: Human Caco-2 apical cell surface and culture medium\nexperimental_model: Differentiated human Caco-2 monolayers; apical ferric nitrilotriacetate and transepithelial transport assays.\nlimitations: Chelator/oxidase interventions support redox dependence; the experiment does not identify every human intestinal transport step.\nexposure: Apical 10 micromolar Fe(III) as 1 Fe:2 NTA, varied ascorbic acid, ascorbate oxidase and Fe(II) chelators.\ncross_nutrient: Vitamin C changes availability of iron for uptake; not proof that all iron absorption requires added vitamin C.\n[c-han1995] Reduction of Fe(III) is required for uptake of nonheme iron by Caco-2 cells (1995). https://pubmed.ncbi.nlm.nih.gov/7738689/ DOI: 10.1093/jn/125.5.1291","model_system":"Differentiated human Caco-2 monolayers; 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Study references: [c-han1995] Reduction of Fe(III) is required for uptake of nonheme iron by Caco-2 cells (1995). https://pubmed.ncbi.nlm.nih.gov/7738689/ DOI: 10.1093/jn/125.5.1291","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}