{"id":"90572245-2a11-5421-8b08-8edaa0365295","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-neuro-gad65-autoinactivation","predicate":"releases-cofactor-during-autoinactivation","statement":"GAD65 catalytic-loop mobility favors a side reaction producing succinic semialdehyde and releasing the converted cofactor as PMP.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"b5a2e164-99cb-5f79-8a17-83d1b6e7b210","mechanism_event_label":"GAD65 can switch into an inactive cofactor-free form.","subject":{"id":"453252f4-83ef-5064-a3f7-21f976f9a3f3","slug":"gad2","display_name":"Human glutamate decarboxylase 65 / GAD2","entity_type_key":"protein"},"object":{"id":"c8dec85c-c85d-5a55-ba85-ad3c1b3e332b","slug":"pyridoxamine-phosphate","display_name":"Pyridoxamine 5-prime-phosphate","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"b5a2e164-99cb-5f79-8a17-83d1b6e7b210","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-neuro-gad65-autoinactivation-event","event_type":"biochemical_relationship","label":"GAD65 can switch into an inactive cofactor-free form.","description":"GAD65 catalytic-loop mobility favors a side reaction producing succinic semialdehyde and releasing the converted cofactor as PMP.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"453252f4-83ef-5064-a3f7-21f976f9a3f3","slug":"gad2","display_name":"Human glutamate decarboxylase 65 / GAD2","entity_type_key":"protein"},"role":"enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6b656ff5-9532-5da4-8eea-8ca163a48649","slug":"pyridoxal-phosphate","display_name":"PLP","entity_type_key":"small_molecule"},"role":"initial-cofactor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"c8dec85c-c85d-5a55-ba85-ad3c1b3e332b","slug":"pyridoxamine-phosphate","display_name":"Pyridoxamine 5-prime-phosphate","entity_type_key":"small_molecule"},"role":"released-cofactor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5f0527f7-04c3-5630-bee7-10f7d6972dc5","slug":"succinic-semialdehyde","display_name":"Succinic semialdehyde","entity_type_key":"small_molecule"},"role":"side-product","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"7da684a4-2641-5bc6-93ae-8c6aa384e487","slug":"glutamate","display_name":"L-Glutamate","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"experimental_model","value_text":"Recombinant human GAD isoforms; crystallography and enzyme kinetics; Human GAD65/GAD67 recombinant chimeras","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Glutamate incubation and enzyme kinetics.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Loop causality is supported by structure and kinetics; cellular net GABA was not measured.","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":"GAD65 can switch into an inactive cofactor-free form.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[fenalti-2007-gad] GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop (2007). https://doi.org/10.1038/nsmb1228 DOI: 10.1038/nsmb1228\n[langendorf-2013-gad] Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates (2013). https://pmc.ncbi.nlm.nih.gov/articles/PMC3546353/ DOI: 10.1042/BSR20120111","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"revision_history","value_text":"[{\"kind\": \"draft-correction\", \"description\": \"Corrected released cofactor identity from PLP to PMP after checking the source; not a scientific conflict.\"}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified recombinant protein; no intact tissue","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"f2efe449-34e3-5a0d-ae35-90d475951fce","evidence_kind":"source_excerpt","locator":"Lines 973-985","start_line":973,"end_line":985,"excerpt":"### b6-neuro-gad65-autoinactivation\nGAD65 catalytic-loop mobility favors a side reaction producing succinic semialdehyde and releasing the converted cofactor as PMP.\nCondition category: normal\nnutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: GAD65 can switch into an inactive cofactor-free form.\norganism: Homo sapiens\ntissue_or_cell_type: Purified recombinant protein; no intact tissue\nexperimental_model: Recombinant human GAD isoforms; crystallography and enzyme kinetics; Human GAD65/GAD67 recombinant chimeras\nlimitations: Loop causality is supported by structure and kinetics; cellular net GABA was not measured.\nexposure: Glutamate incubation and enzyme kinetics.\nrevision_history: [{\"kind\": \"draft-correction\", \"description\": \"Corrected released cofactor identity from PLP to PMP after checking the source; not a scientific conflict.\"}]\n[fenalti-2007-gad] GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop (2007). https://doi.org/10.1038/nsmb1228 DOI: 10.1038/nsmb1228\n[langendorf-2013-gad] Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates (2013). https://pmc.ncbi.nlm.nih.gov/articles/PMC3546353/ DOI: 10.1042/BSR20120111","model_system":"Recombinant human GAD isoforms; crystallography and enzyme kinetics; Human GAD65/GAD67 recombinant chimeras","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [fenalti-2007-gad] GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop (2007). https://doi.org/10.1038/nsmb1228 DOI: 10.1038/nsmb1228; [langendorf-2013-gad] Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates (2013). https://pmc.ncbi.nlm.nih.gov/articles/PMC3546353/ DOI: 10.1042/BSR20120111","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}