{"id":"88d94795-f1d0-55ee-a191-81322cfb299c","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-neuro-aldh7a1-metabolite-accumulation","predicate":"increases","statement":"The antiquitin defect was linked to accumulation of alpha-AASA/P6C in the lysine degradation pathway.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"e78abbda-21ea-5b68-908d-bd0f7e071a83","mechanism_event_label":"A blocked lysine pathway builds up B6-reactive metabolites.","subject":{"id":"50591653-9411-5b3d-a08d-1b825c96abad","slug":"aldh7a1-disease-genotypes","display_name":"Biallelic ALDH7A1 disease genotypes studied by Mills 2006","entity_type_key":"gene"},"object":{"id":"9a7b1d83-ebb2-5dea-b4a7-c040502fba4d","slug":"piperideine-6-carboxylate","display_name":"Delta1-piperideine-6-carboxylate","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"e78abbda-21ea-5b68-908d-bd0f7e071a83","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-neuro-aldh7a1-metabolite-accumulation-event","event_type":"biochemical_relationship","label":"A blocked lysine pathway builds up B6-reactive metabolites.","description":"The antiquitin defect was linked to accumulation of alpha-AASA/P6C in the lysine degradation pathway.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"50591653-9411-5b3d-a08d-1b825c96abad","slug":"aldh7a1-disease-genotypes","display_name":"Biallelic ALDH7A1 disease genotypes studied by Mills 2006","entity_type_key":"gene"},"role":"genetic-perturbation","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"7d67a576-2d6f-5556-863c-d1dfd273f687","slug":"alpha-aminoadipate-semialdehyde","display_name":"alpha-Aminoadipate semialdehyde","entity_type_key":"small_molecule"},"role":"accumulating-metabolite","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"9a7b1d83-ebb2-5dea-b4a7-c040502fba4d","slug":"piperideine-6-carboxylate","display_name":"Delta1-piperideine-6-carboxylate","entity_type_key":"small_molecule"},"role":"cyclic-metabolite","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5fff6664-209e-5c35-b88e-ac15c1c5fbc0","slug":"l-lysine","display_name":"L-Lysine","entity_type_key":"small_molecule"},"role":"upstream-nutrient","stoichiometry":null,"state_label":"","sequence_order":3,"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":"Lysine catabolism generates the metabolite that can sequester PLP.","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":"ALDH7A1-associated disease and metabolite analysis.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This is inherited pathway failure, not lysine toxicity in healthy people.","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 blocked lysine pathway builds up B6-reactive metabolites.","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":"Patient biological samples and biochemical pathway analysis","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":"bab26921-56f5-50c7-bba3-773e81a86c01","evidence_kind":"source_excerpt","locator":"Lines 1158-1169","start_line":1158,"end_line":1169,"excerpt":"### b6-neuro-aldh7a1-metabolite-accumulation\nThe antiquitin defect was linked to accumulation of alpha-AASA/P6C in the lysine degradation pathway.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A blocked lysine pathway builds up B6-reactive metabolites.\norganism: Homo sapiens\ntissue_or_cell_type: Patient biological samples and biochemical pathway analysis\nexperimental_model: Affected children, expressed human ALDH7A1 variants and metabolite chemistry\nlimitations: This is inherited pathway failure, not lysine toxicity in healthy people.\nexposure: ALDH7A1-associated disease and metabolite analysis.\ncross_nutrient: Lysine catabolism generates the metabolite that can sequester PLP.\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}