{"id":"804b2b81-8fd8-5a5a-b8b7-2012383b0ce2","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-iron-transepithelial-flux","predicate":"increases_iron_flux_across_caco2_monolayers","statement":"Apical ascorbic acid at 100 and 1000 micromolar increased apical-to-basolateral iron transport 5.6-fold and 30-fold, respectively, in the ferric-NTA system.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"a7fed482-83d9-5bc8-a33f-443c583e38e7","mechanism_event_label":"More iron crossed the model cell layer under those experimental conditions.","subject":{"id":"2047867f-9872-53b2-a553-71c911d0695b","slug":"ascorbic-acid","display_name":"L-Ascorbic acid","entity_type_key":"small_molecule"},"object":{"id":"fa597da6-d666-54fe-ae34-7004a7b38895","slug":"caco2-transepithelial-iron-flux","display_name":"Caco-2 transepithelial iron flux","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"a7fed482-83d9-5bc8-a33f-443c583e38e7","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-iron-transepithelial-flux-event","event_type":"biochemical_relationship","label":"More iron crossed the model cell layer under those experimental conditions.","description":"Apical ascorbic acid at 100 and 1000 micromolar increased apical-to-basolateral iron transport 5.6-fold and 30-fold, respectively, in the ferric-NTA system.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"89bcaf42-b4ab-5760-8c2e-44eace10cee0","slug":"iron","display_name":"Iron","entity_type_key":"nutrient_element"},"role":"transported_nutrient","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"2047867f-9872-53b2-a553-71c911d0695b","slug":"ascorbic-acid","display_name":"L-Ascorbic acid","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"fa597da6-d666-54fe-ae34-7004a7b38895","slug":"caco2-transepithelial-iron-flux","display_name":"Caco-2 transepithelial iron flux","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Direct vitamin C/iron transport experiment.","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":"Culture concentrations and ligand system cannot be converted into a human absorption percentage.","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":"More iron crossed the model cell layer under those experimental conditions.","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 monolayers","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"c94f7980-534e-5d17-b863-501306210bef","evidence_kind":"source_excerpt","locator":"Lines 1567-1578","start_line":1567,"end_line":1578,"excerpt":"### c-iron-transepithelial-flux\nApical ascorbic acid at 100 and 1000 micromolar increased apical-to-basolateral iron transport 5.6-fold and 30-fold, respectively, in the ferric-NTA system.\nCondition category: normal\nnutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: More iron crossed the model cell layer under those experimental conditions.\norganism: Homo sapiens\ntissue_or_cell_type: Human Caco-2 monolayers\nexperimental_model: Differentiated human Caco-2 monolayers; apical ferric nitrilotriacetate and transepithelial transport assays.\nlimitations: Culture concentrations and ligand system cannot be converted into a human absorption percentage.\nexposure: Apical 10 micromolar Fe(III) as 1 Fe:2 NTA, varied ascorbic acid, ascorbate oxidase and Fe(II) chelators.\ncross_nutrient: Direct vitamin C/iron transport experiment.\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; apical ferric nitrilotriacetate and transepithelial transport assays.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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}