{"id":"fb59ed53-0501-506e-b4b3-d93b891467cb","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-trans-zip8-zinc-inhibits-iron","predicate":"inhibits","statement":"A tenfold molar excess of zinc inhibited iron uptake by more than 90% in rat ZIP8-expressing HEK293T cells under the study conditions.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"46ca4c39-e534-51ba-b72c-f7c057f4da4a","mechanism_event_label":"Zinc strongly reduced iron entry in this cultured transport system.","subject":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"object":{"id":"05ee8d96-f499-5bcd-a50f-1c58646d20aa","slug":"cellular-iron-uptake","display_name":"Cellular iron uptake","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"46ca4c39-e534-51ba-b72c-f7c057f4da4a","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-trans-zip8-zinc-inhibits-iron-event","event_type":"biochemical_relationship","label":"Zinc strongly reduced iron entry in this cultured transport system.","description":"A tenfold molar excess of zinc inhibited iron uptake by more than 90% in rat ZIP8-expressing HEK293T cells under the study conditions.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"ba09e4ed-8b9c-5cd9-bea8-6f8527090978","slug":"rat-slc39a8","display_name":"Rat ZIP8 (Slc39a8)","entity_type_key":"protein"},"role":"transporter","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":"inhibited_substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"05ee8d96-f499-5bcd-a50f-1c58646d20aa","slug":"cellular-iron-uptake","display_name":"Cellular iron uptake","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Rat ZIP8-expressing HEK293T radiotracer assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"2 micromolar labeled iron with ascorbate and tenfold unlabeled zinc excess.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The assay contains reduction chemistry and soluble ions; this is not direct evidence for the magnitude of human meal-iron inhibition.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Zinc research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"zinc","display_name":"Zinc","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Rat protein in human cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Zinc strongly reduced iron entry in this cultured transport system.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HEK293T cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"dc50c914-0469-5539-8224-2a484b927943","evidence_kind":"source_excerpt","locator":"Lines 453-464","start_line":453,"end_line":464,"excerpt":"### zinc-trans-zip8-zinc-inhibits-iron\nA tenfold molar excess of zinc inhibited iron uptake by more than 90% in rat ZIP8-expressing HEK293T cells under the study conditions.\nCondition category: normal\nnutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Zinc strongly reduced iron entry in this cultured transport system.\norganism: Rat protein in human cells\ntissue_or_cell_type: HEK293T cells\nexperimental_model: Rat ZIP8-expressing HEK293T radiotracer assay\nlimitations: The assay contains reduction chemistry and soluble ions; this is not direct evidence for the magnitude of human meal-iron inhibition.\nexposure: 2 micromolar labeled iron with ascorbate and tenfold unlabeled zinc excess.\ncross_nutrient: true\n[zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284","model_system":"Rat ZIP8-expressing HEK293T radiotracer assay","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c5ee0fee-ce5c-58de-905a-10fb0ea0723c","stable_key":"import-6d38d43e-01e4-5641-93be-65654271e242","title":"Zinc: transport, enzyme loading, 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. 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