{"id":"843e5f9d-3084-57c5-9dfb-b91649429981","stable_key":"b7014def-74ec-599e-8347-167e24fec1f0:glutamate-vglut2-acetoacetate","predicate":"inhibits","statement":"Acetoacetate reversibly inhibited reconstituted rat VGLUT2 uptake with a chloride-dependent shift consistent with competition at allosteric regulation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"e48d329c-2b2a-5d66-93a8-82c85a917758","mechanism_event_label":"A metabolic fuel-related molecule altered transmitter packaging in a biochemical system.","subject":{"id":"1b77cb4a-1f79-50e2-b4f0-fd0953cb914e","slug":"acetoacetate","display_name":"Acetoacetate","entity_type_key":"small_molecule"},"object":{"id":"336a46b8-622b-5f7d-8075-a56f55eba636","slug":"rat-slc17a6","display_name":"Rat vesicular glutamate transporter 2 / Slc17a6","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"e48d329c-2b2a-5d66-93a8-82c85a917758","stable_key":"b7014def-74ec-599e-8347-167e24fec1f0:glutamate-vglut2-acetoacetate-event","event_type":"observed_relationship","label":"A metabolic fuel-related molecule altered transmitter packaging in a biochemical system.","description":"Acetoacetate reversibly inhibited reconstituted rat VGLUT2 uptake with a chloride-dependent shift consistent with competition at allosteric regulation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"1b77cb4a-1f79-50e2-b4f0-fd0953cb914e","slug":"acetoacetate","display_name":"Acetoacetate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"336a46b8-622b-5f7d-8075-a56f55eba636","slug":"rat-slc17a6","display_name":"Rat vesicular glutamate transporter 2 / Slc17a6","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":"6f35aa38-f875-5759-b749-97a2f6480ff3","slug":"chloride-ion","display_name":"Chloride ion","entity_type_key":"ion"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified rat transporter; controlled chloride/acetoacetate concentrations and washout.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This mechanism alone does not establish the effects of fasting or a ketogenic diet in humans.","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 metabolic fuel-related molecule altered transmitter packaging in a biochemical system.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"40bd6702-5204-5e22-88d5-eb92f9aa535c","evidence_kind":"source_excerpt","locator":"Lines 282-288","start_line":282,"end_line":288,"excerpt":"## glutamate-vglut2-acetoacetate\nA metabolic fuel-related molecule altered transmitter packaging in a biochemical system.\nAcetoacetate reversibly inhibited reconstituted rat VGLUT2 uptake with a chloride-dependent shift consistent with competition at allosteric regulation.\nModel: Purified rat transporter; controlled chloride/acetoacetate concentrations and washout.\nLimitations: This mechanism alone does not establish the effects of fasting or a ketogenic diet in humans.\nEvidence access: Primary full text\nMetabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002","model_system":"Purified rat transporter; controlled chloride/acetoacetate concentrations and washout.","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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