{"id":"102b38ae-6dcf-5bfc-88b6-1305c35f5734","stable_key":"b7014def-74ec-599e-8347-167e24fec1f0:glutamate-glul-human-loss","predicate":"impairs","statement":"Two infants with homozygous GLUL mutations had profoundly low glutamine and severe neonatal disease; variant expression assays showed reduced enzyme activity.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"57ad5297-d449-5bf0-9bc5-cbe564d1c9e5","mechanism_event_label":"A synthesis defect can prevent conversion of one available amino acid into another.","subject":{"id":"48bf275d-f9b8-51eb-810f-a74e790df155","slug":"human-glul-r324c-r341c","display_name":"Human GLUL R324C/R341C deficiency","entity_type_key":"cellular_process"},"object":{"id":"d38cfc9c-9372-5e5f-8d91-03098155a3c6","slug":"glul","display_name":"Glutamine synthetase / GLUL","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"57ad5297-d449-5bf0-9bc5-cbe564d1c9e5","stable_key":"b7014def-74ec-599e-8347-167e24fec1f0:glutamate-glul-human-loss-event","event_type":"observed_relationship","label":"A synthesis defect can prevent conversion of one available amino acid into another.","description":"Two infants with homozygous GLUL mutations had profoundly low glutamine and severe neonatal disease; variant expression assays showed reduced enzyme activity.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"48bf275d-f9b8-51eb-810f-a74e790df155","slug":"human-glul-r324c-r341c","display_name":"Human GLUL R324C/R341C deficiency","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d38cfc9c-9372-5e5f-8d91-03098155a3c6","slug":"glul","display_name":"Glutamine synthetase / GLUL","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7da684a4-2641-5bc6-93ae-8c6aa384e487","slug":"glutamate","display_name":"L-Glutamate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"8637bb39-2c30-5168-baaf-3e613d831db0","slug":"glutamine","display_name":"L-Glutamine","entity_type_key":"small_molecule"},"role":"context_participant","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":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Two unrelated newborns, patient lymphocytes and mutant expression in COS7 cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This is congenital glutamine-synthesis failure, not evidence of inadequate dietary glutamate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"glutamate","display_name":"L-Glutamate","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A synthesis defect can prevent conversion of one available amino acid into another.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Congenital glutamine deficiency with glutamine synthetase mutations. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16267323/ · DOI 10.1056/NEJMoa050456","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":"2cc6f019-7379-5bed-8ef0-6d8bf6854fb1","evidence_kind":"source_excerpt","locator":"Lines 122-128","start_line":122,"end_line":128,"excerpt":"## glutamate-glul-human-loss\nA synthesis defect can prevent conversion of one available amino acid into another.\nTwo infants with homozygous GLUL mutations had profoundly low glutamine and severe neonatal disease; variant expression assays showed reduced enzyme activity.\nModel: Two unrelated newborns, patient lymphocytes and mutant expression in COS7 cells.\nLimitations: This is congenital glutamine-synthesis failure, not evidence of inadequate dietary glutamate.\nEvidence access: Primary abstract\nCongenital glutamine deficiency with glutamine synthetase mutations. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16267323/ · DOI 10.1056/NEJMoa050456","model_system":"Two unrelated newborns, patient lymphocytes and mutant expression in COS7 cells.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c6a55239-e808-5ed7-9fa3-755a18ecb29f","stable_key":"import-b7014def-74ec-599e-8347-167e24fec1f0","title":"L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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