{"id":"7d3b895f-a8bd-5cad-82ce-c73d68b21d8e","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-reg-aconitase-inactivation","predicate":"decreases-peroxide-dependent","statement":"Pharmacological ascorbate decreased total cellular aconitase activity in NSCLC cultures; catalase overexpression prevented this activity loss, implicating peroxide-dependent injury to the Fe-S enzyme system.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"cdf5cfb8-4874-5668-ab17-c1a97ef1a369","mechanism_event_label":"High-concentration vitamin C impaired an iron-sulfur enzyme in these cancer cells, and removing peroxide protected its activity.","subject":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"object":{"id":"aa783e22-04fc-5263-9ac2-bb643d45ff08","slug":"cellular-aconitase-activity","display_name":"Total cellular aconitase activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"cdf5cfb8-4874-5668-ab17-c1a97ef1a369","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-reg-aconitase-inactivation-event","event_type":"biochemical_relationship","label":"High-concentration vitamin C impaired an iron-sulfur enzyme in these cancer cells, and removing peroxide protected its activity.","description":"Pharmacological ascorbate decreased total cellular aconitase activity in NSCLC cultures; catalase overexpression prevented this activity loss, implicating peroxide-dependent injury to the Fe-S enzyme system.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"da1a7137-08f2-5a36-8bb6-377fbd32e327","slug":"vitamin-c","display_name":"Vitamin C","entity_type_key":"chemical_species"},"role":"nutrient context","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8058ae47-b091-5004-ba65-1e50ad91f70b","slug":"iron-sulfur-4fe4s","display_name":"[4Fe-4S] iron-sulfur cluster","entity_type_key":"chemical_species"},"role":"susceptible catalytic cluster","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"da9d64bc-69d4-5d97-90a4-8f0ed03e0ac8","slug":"hydrogen-peroxide","display_name":"Hydrogen peroxide","entity_type_key":"small_molecule"},"role":"causal mediator tested by rescue","stoichiometry":null,"state_label":"","sequence_order":2,"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":3,"notes":""},{"entity":{"id":"aa783e22-04fc-5263-9ac2-bb643d45ff08","slug":"cellular-aconitase-activity","display_name":"Total cellular aconitase activity","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Figure 6C","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human NSCLC cells cultured in RPMI-1640 +10% FBS; L-ascorbic acid stocks neutralized to pH 7.0; total-cell aconitase activity assay and adenoviral catalase rescue","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"15 pmol ascorbate/cell (approximately 8 mM), 1 h; catalase rescue 50-MOI vector transduction 36 h before treatment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Short pharmacological culture exposure; dose per cell, medium and density alter toxicity. Enzyme activity loss is consistent with Fe-S damage but does not directly trace individual iron atoms leaving a cluster. Total assay does not resolve cytosolic ACO1 from mitochondrial ACO2.","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":"High-concentration vitamin C impaired an iron-sulfur enzyme in these cancer cells, and removing peroxide protected its activity.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[c-reg-schoenfeld] O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. (2017). https://pubmed.ncbi.nlm.nih.gov/28366679/ DOI: 10.1016/j.ccell.2017.02.018","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"NSCLC cell cultures","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"bb9f0e4e-62ee-5791-8aab-c5c4e5c774a7","evidence_kind":"source_excerpt","locator":"Lines 1327-1339","start_line":1327,"end_line":1339,"excerpt":"### c-reg-aconitase-inactivation\nPharmacological ascorbate decreased total cellular aconitase activity in NSCLC cultures; catalase overexpression prevented this activity loss, implicating peroxide-dependent injury to the Fe-S enzyme system.\nCondition category: normal\nnutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: High-concentration vitamin C impaired an iron-sulfur enzyme in these cancer cells, and removing peroxide protected its activity.\norganism: Homo sapiens\ntissue_or_cell_type: NSCLC cell cultures\nexperimental_model: Human NSCLC cells cultured in RPMI-1640 +10% FBS; L-ascorbic acid stocks neutralized to pH 7.0; total-cell aconitase activity assay and adenoviral catalase rescue\nlimitations: Short pharmacological culture exposure; dose per cell, medium and density alter toxicity. Enzyme activity loss is consistent with Fe-S damage but does not directly trace individual iron atoms leaving a cluster. Total assay does not resolve cytosolic ACO1 from mitochondrial ACO2.\nexposure: 15 pmol ascorbate/cell (approximately 8 mM), 1 h; catalase rescue 50-MOI vector transduction 36 h before treatment.\ncross_nutrient: true\nevidence_location: Figure 6C\n[c-reg-schoenfeld] O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. (2017). https://pubmed.ncbi.nlm.nih.gov/28366679/ DOI: 10.1016/j.ccell.2017.02.018","model_system":"Human NSCLC cells cultured in RPMI-1640 +10% FBS; L-ascorbic acid stocks neutralized to pH 7.0; total-cell aconitase activity assay and adenoviral catalase rescue","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [c-reg-schoenfeld] O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. (2017). https://pubmed.ncbi.nlm.nih.gov/28366679/ DOI: 10.1016/j.ccell.2017.02.018","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}