{"id":"952a0e88-f17f-5100-a216-c89fa815ffab","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-neuro-pih-fech-protein","predicate":"reduces","statement":"PIH treatment lowered FECH protein without lowering FECH mRNA in human liver-cell models.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"80f76596-6ac1-58f3-89e7-dd9b7fc6c7bd","mechanism_event_label":"A drug-B6 conjugate affected a heme-making enzyme.","subject":{"id":"af123b94-0b58-5894-83f0-9b8e681b8fe5","slug":"pyridoxal-isonicotinoyl-hydrazone","display_name":"Pyridoxal isonicotinoyl hydrazone","entity_type_key":"small_molecule"},"object":{"id":"b62a3c7f-ddf3-59e8-86c8-6d00c041aa21","slug":"fech","display_name":"Human ferrochelatase / FECH","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"80f76596-6ac1-58f3-89e7-dd9b7fc6c7bd","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-neuro-pih-fech-protein-event","event_type":"biochemical_relationship","label":"A drug-B6 conjugate affected a heme-making enzyme.","description":"PIH treatment lowered FECH protein without lowering FECH mRNA in human liver-cell models.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"af123b94-0b58-5894-83f0-9b8e681b8fe5","slug":"pyridoxal-isonicotinoyl-hydrazone","display_name":"Pyridoxal isonicotinoyl hydrazone","entity_type_key":"small_molecule"},"role":"exposure","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b62a3c7f-ddf3-59e8-86c8-6d00c041aa21","slug":"fech","display_name":"Human ferrochelatase / FECH","entity_type_key":"protein"},"role":"affected-enzyme","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"89bcaf42-b4ab-5760-8c2e-44eace10cee0","slug":"iron","display_name":"Iron","entity_type_key":"nutrient_element"},"role":"interacting-nutrient","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"B6-drug conjugation connects to iron-sensitive heme machinery.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cell-free chemistry, primary human hepatocytes and HepG2/C3A cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"100 micromolar PIH for 16 hours in the initial HepG2/C3A comparison; 24-hour PIH dose-response assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Direct destruction of the FECH iron-sulfur cluster was not demonstrated.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-b6","display_name":"Vitamin B6","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A drug-B6 conjugate affected a heme-making enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[brewer-2019-isoniazid] The Isoniazid Metabolites Hydrazine and Pyridoxal Isonicotinoyl Hydrazone Modulate Heme Biosynthesis (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6390808/ DOI: 10.1093/toxsci/kfy294","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Primary human hepatocytes and HepG2/C3A cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; 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Study references: [brewer-2019-isoniazid] The Isoniazid Metabolites Hydrazine and Pyridoxal Isonicotinoyl Hydrazone Modulate Heme Biosynthesis (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6390808/ DOI: 10.1093/toxsci/kfy294","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"251773bb-16f5-5903-b135-db4a61d9dec4","stable_key":"import-1310afbd-6010-586e-805d-551d846da421","title":"Vitamin B6: 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":"ef0019b344b2219220f801a84d0d138ff6880c1be1a59540d9034bfa4334f61e","revision_id":"cac3555f-48af-5c52-a84e-add4482c87fb","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}