{"id":"7c629d7d-335e-5d5d-800e-1a801e5a3307","stable_key":"27e0c1cf-7726-5164-8b15-27a631584cd0:choline-chat-e441k","predicate":"abolishes_in_assay","statement":"Bacterially expressed human ChAT E441K lacked catalytic activity in the reported kinetic experiment.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"cfe14771-ca86-5c12-9768-94d9fb042748","mechanism_event_label":"Having the nutrient present cannot by itself guarantee synthesis when the enzyme is inactive.","subject":{"id":"433f7712-d5f9-57e4-91c5-d7c2b4849643","slug":"chat-e441k","display_name":"Human ChAT E441K construct in the 2001 study","entity_type_key":"protein_state"},"object":{"id":"5cca6007-b83d-5b13-86ca-f61b244f2f3d","slug":"human-chat-acetylcholine-synthesis","display_name":"Human ChAT acetylcholine synthesis activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"cfe14771-ca86-5c12-9768-94d9fb042748","stable_key":"27e0c1cf-7726-5164-8b15-27a631584cd0:choline-chat-e441k-event","event_type":"biochemical_relationship","label":"Having the nutrient present cannot by itself guarantee synthesis when the enzyme is inactive.","description":"Bacterially expressed human ChAT E441K lacked catalytic activity in the reported kinetic experiment.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a137a526-2735-5ba4-9090-0d686bfa6572","slug":"chat","display_name":"Human choline acetyltransferase / CHAT","entity_type_key":"protein"},"role":"affected_enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"433f7712-d5f9-57e4-91c5-d7c2b4849643","slug":"chat-e441k","display_name":"Human ChAT E441K construct in the 2001 study","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"5cca6007-b83d-5b13-86ca-f61b244f2f3d","slug":"human-chat-acetylcholine-synthesis","display_name":"Human ChAT acetylcholine synthesis activity","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/choline-research/11172068.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"691b96b9c5c149c554b99d8e1532ffee25084a8970f8deb23f0991dfd6013d39\", \"start_char\": 0, \"end_char\": 1231, \"text_sha256\": \"691b96b9c5c149c554b99d8e1532ffee25084a8970f8deb23f0991dfd6013d39\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human CHAT genetics, recombinant expression and enzyme kinetics","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Ten recessive variants in five patients; nine mutant proteins assayed","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Inherited enzyme defects, not a dietary choline-deficiency model. Acetyl-CoA and choline are distinct substrates.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Choline research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"choline","display_name":"Choline","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human CHAT proteins; COS-cell and bacterial expression systems","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Having the nutrient present cannot by itself guarantee synthesis when the enzyme is inactive.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[choline-p11172068] Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11172068/ DOI: 10.1073/pnas.98.4.2017","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Neuromuscular acetylcholine resynthesis","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":"6d5bd104-1c23-5f84-a427-c389a9b184fa","evidence_kind":"source_excerpt","locator":"Lines 425-436","start_line":425,"end_line":436,"excerpt":"### choline-chat-e441k\nBacterially expressed human ChAT E441K lacked catalytic activity in the reported kinetic experiment.\nCondition category: machinery_impairment\nnutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Having the nutrient present cannot by itself guarantee synthesis when the enzyme is inactive.\norganism: Human CHAT proteins; COS-cell and bacterial expression systems\ntissue_or_cell_type: Neuromuscular acetylcholine resynthesis\nexperimental_model: Human CHAT genetics, recombinant expression and enzyme kinetics\nlimitations: Inherited enzyme defects, not a dietary choline-deficiency model. Acetyl-CoA and choline are distinct substrates.\nexposure: Ten recessive variants in five patients; nine mutant proteins assayed\nevidence_span: {\"source_cache\": \"artifacts/choline-research/11172068.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"691b96b9c5c149c554b99d8e1532ffee25084a8970f8deb23f0991dfd6013d39\", \"start_char\": 0, \"end_char\": 1231, \"text_sha256\": \"691b96b9c5c149c554b99d8e1532ffee25084a8970f8deb23f0991dfd6013d39\"}\n[choline-p11172068] Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11172068/ DOI: 10.1073/pnas.98.4.2017","model_system":"Human CHAT genetics, recombinant expression and enzyme kinetics","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [choline-p11172068] Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11172068/ DOI: 10.1073/pnas.98.4.2017","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"0ba2f05e-5cf5-5bd7-ae5d-0ab4945fcb7b","stable_key":"import-27e0c1cf-7726-5164-8b15-27a631584cd0","title":"Choline: metabolism, signaling and nutrient connections (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":"c7afe3d579eba0df6d2a4c26699c653462749e03188348f900c07748cc7282a8","revision_id":"0fa7b48f-2a3c-5adc-b13e-48727dd6f815","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}