{"id":"42508c5d-8922-579c-8b03-8b8f46d9da55","stable_key":"b7014def-74ec-599e-8347-167e24fec1f0:glutamate-gdh-gtp-control","predicate":"inhibits","statement":"Human GLUD1 activity was inhibited by GTP; patient-derived regulatory variants showed reduced sensitivity to that inhibition.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"1fb84b77-c9d0-57de-b1e9-b16e9569d3fb","mechanism_event_label":"An energy-related nucleotide restrains glutamate oxidation.","subject":{"id":"c8ccc03a-29cc-5127-baf5-81eeb92ac780","slug":"gtp","display_name":"Guanosine triphosphate","entity_type_key":"small_molecule"},"object":{"id":"7a2271b6-fae8-5b08-b6ae-df7a0f96919b","slug":"glud1","display_name":"GLUD1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"1fb84b77-c9d0-57de-b1e9-b16e9569d3fb","stable_key":"b7014def-74ec-599e-8347-167e24fec1f0:glutamate-gdh-gtp-control-event","event_type":"observed_relationship","label":"An energy-related nucleotide restrains glutamate oxidation.","description":"Human GLUD1 activity was inhibited by GTP; 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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":"An energy-related nucleotide restrains glutamate oxidation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9571255/ · DOI 10.1056/NEJM199805073381904","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"5b59e26f-49db-57f4-a317-953514ae68be","evidence_kind":"source_excerpt","locator":"Lines 170-176","start_line":170,"end_line":176,"excerpt":"## glutamate-gdh-gtp-control\nAn energy-related nucleotide restrains glutamate oxidation.\nHuman GLUD1 activity was inhibited by GTP; patient-derived regulatory variants showed reduced sensitivity to that inhibition.\nModel: Human lymphoblast enzyme assays from eight unrelated affected children and controls.\nLimitations: GTP regulation is not evidence that dietary purines or glutamate normalize the disease.\nEvidence access: Primary abstract\nHyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9571255/ · DOI 10.1056/NEJM199805073381904","model_system":"Human lymphoblast enzyme assays from eight unrelated affected children and controls.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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