{"id":"46e77cd6-0d62-5b47-8ccf-6e8fd2710c7d","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-neuro-p6c-plp-sequestration","predicate":"chemically-inactivates","statement":"P6C reacts with PLP to form a Knoevenagel condensation product that inactivates the cofactor.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"9019bbff-4c27-5002-9d0b-526488488560","mechanism_event_label":"The accumulated lysine metabolite chemically traps activated B6.","subject":{"id":"9a7b1d83-ebb2-5dea-b4a7-c040502fba4d","slug":"piperideine-6-carboxylate","display_name":"Delta1-piperideine-6-carboxylate","entity_type_key":"small_molecule"},"object":{"id":"6b656ff5-9532-5da4-8eea-8ca163a48649","slug":"pyridoxal-phosphate","display_name":"PLP","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"9019bbff-4c27-5002-9d0b-526488488560","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-neuro-p6c-plp-sequestration-event","event_type":"biochemical_relationship","label":"The accumulated lysine metabolite chemically traps activated B6.","description":"P6C reacts with PLP to form a Knoevenagel condensation product that inactivates the cofactor.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9a7b1d83-ebb2-5dea-b4a7-c040502fba4d","slug":"piperideine-6-carboxylate","display_name":"Delta1-piperideine-6-carboxylate","entity_type_key":"small_molecule"},"role":"reactant","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6b656ff5-9532-5da4-8eea-8ca163a48649","slug":"pyridoxal-phosphate","display_name":"PLP","entity_type_key":"small_molecule"},"role":"reactant","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"f77e1b69-046e-54c2-89f1-4564fc5a539a","slug":"plp-p6c-condensation-product","display_name":"PLP-P6C Knoevenagel condensation product","entity_type_key":"small_molecule"},"role":"product","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":"Direct lysine-metabolite to vitamin-B6 antagonism.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Affected children, expressed human ALDH7A1 variants and metabolite chemistry","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Biochemical P6C-PLP reaction.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Direct chemistry supports sequestration; it does not quantify PLP loss in every neuronal compartment.","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":"The accumulated lysine metabolite chemically traps activated B6.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mills-2006-aldh7a1] Mutations in antiquitin in individuals with pyridoxine-dependent seizures (2006). https://doi.org/10.1038/nm1366 DOI: 10.1038/nm1366","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cell-free chemistry","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"a61d8af3-21c9-590f-8bda-5a4504a28e9a","evidence_kind":"source_excerpt","locator":"Lines 1171-1182","start_line":1171,"end_line":1182,"excerpt":"### b6-neuro-p6c-plp-sequestration\nP6C reacts with PLP to form a Knoevenagel condensation product that inactivates the cofactor.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The accumulated lysine metabolite chemically traps activated B6.\norganism: Homo sapiens\ntissue_or_cell_type: Cell-free chemistry\nexperimental_model: Affected children, expressed human ALDH7A1 variants and metabolite chemistry\nlimitations: Direct chemistry supports sequestration; it does not quantify PLP loss in every neuronal compartment.\nexposure: Biochemical P6C-PLP reaction.\ncross_nutrient: Direct lysine-metabolite to vitamin-B6 antagonism.\n[mills-2006-aldh7a1] Mutations in antiquitin in individuals with pyridoxine-dependent seizures (2006). https://doi.org/10.1038/nm1366 DOI: 10.1038/nm1366","model_system":"Affected children, expressed human ALDH7A1 variants and metabolite chemistry","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [mills-2006-aldh7a1] Mutations in antiquitin in individuals with pyridoxine-dependent seizures (2006). https://doi.org/10.1038/nm1366 DOI: 10.1038/nm1366","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}