{"id":"856e0fcb-faad-557c-8e35-8a74ef70d8fc","stable_key":"c3df3634-4c3a-5099-a5d9-e4f6344c1084:gcdh-high-lysine-glutarate","predicate":"impairment_accumulates","statement":"High lysine intake in Gcdh-null mice increases glutarate accumulation and produces age-dependent brain injury.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"a50dcab3-5f53-5b8e-9437-ee796424d341","mechanism_event_label":"Lysine loading can worsen a blocked breakdown pathway.","subject":{"id":"27a3d8c4-8a68-5288-aa1e-6cbeb663f463","slug":"gcdh","display_name":"Glutaryl-CoA dehydrogenase / GCDH","entity_type_key":"protein"},"object":{"id":"0c9a7ccc-f689-52ae-b3b6-bb461b27ff97","slug":"glutarate","display_name":"Glutarate","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"a50dcab3-5f53-5b8e-9437-ee796424d341","stable_key":"c3df3634-4c3a-5099-a5d9-e4f6344c1084:gcdh-high-lysine-glutarate-event","event_type":"biochemical_relationship","label":"Lysine loading can worsen a blocked breakdown pathway.","description":"High lysine intake in Gcdh-null mice increases glutarate accumulation and produces age-dependent brain injury.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"27a3d8c4-8a68-5288-aa1e-6cbeb663f463","slug":"gcdh","display_name":"Glutaryl-CoA dehydrogenase / GCDH","entity_type_key":"protein"},"role":"impaired_machinery","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"5fff6664-209e-5c35-b88e-ac15c1c5fbc0","slug":"l-lysine","display_name":"L-Lysine","entity_type_key":"small_molecule"},"role":"upstream_substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"0c9a7ccc-f689-52ae-b3b6-bb461b27ff97","slug":"glutarate","display_name":"Glutarate","entity_type_key":"small_molecule"},"role":"accumulating_metabolite","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"f83f2113-a4de-5cdf-bda7-84fe4582785b","slug":"striatal-injury","display_name":"Striatal injury","entity_type_key":"cellular_process"},"role":"outcome","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"affected_machinery","value_text":"GCDH","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"deficiency_not_equivalent","value_text":"Nutrient deficiency or normal human lysine intake","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"High-lysine dietary challenge of Gcdh-knockout mice","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Genetic susceptibility and age are essential; does not show comparable toxicity in healthy humans.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Lysine loading can worsen a blocked breakdown pathway.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[zinnanti2006] A diet-induced mouse model for glutaric aciduria type I (2006). https://pubmed.ncbi.nlm.nih.gov/16446282/ DOI: 10.1093/brain/awl009","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Brain and systemic circulation","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":"c7145f01-c6c0-5306-965a-82d402bcfe8f","evidence_kind":"source_excerpt","locator":"Lines 290-300","start_line":290,"end_line":300,"excerpt":"### gcdh-high-lysine-glutarate\nHigh lysine intake in Gcdh-null mice increases glutarate accumulation and produces age-dependent brain injury.\nPlain language: Lysine loading can worsen a blocked breakdown pathway.\nCondition category: machinery_impairment\norganism: Mus musculus\ntissue_or_cell_type: Brain and systemic circulation\nexperimental_model: High-lysine dietary challenge of Gcdh-knockout mice\nlimitations: Genetic susceptibility and age are essential; does not show comparable toxicity in healthy humans.\naffected_machinery: GCDH\ndeficiency_not_equivalent: Nutrient deficiency or normal human lysine intake\n[zinnanti2006] A diet-induced mouse model for glutaric aciduria type I (2006). https://pubmed.ncbi.nlm.nih.gov/16446282/ DOI: 10.1093/brain/awl009","model_system":"High-lysine dietary challenge of Gcdh-knockout mice","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact quote from the accompanying curation document, not from publisher text. Original study references: [zinnanti2006] A diet-induced mouse model for glutaric aciduria type I (2006). https://pubmed.ncbi.nlm.nih.gov/16446282/ DOI: 10.1093/brain/awl009","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"7633bde7-dcc9-5086-91c6-a45eb96857f3","stable_key":"import-c3df3634-4c3a-5099-a5d9-e4f6344c1084","title":"L-Lysine: mechanism-first literature curation (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":"93998d47c21525409ba82f1c82ededf2893dff15fbe61c7deffc175b0e298e97","revision_id":"3897e31f-6624-59e1-a053-8a81b7361632","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}