{"id":"94b5e1d1-fdea-54fd-be17-f71064c67510","stable_key":"f992b796-377d-53bf-a39b-7e5d41dbe194:b5-bio-coasy-r499c-activity","predicate":"loses_detectable_phosphorylation_of","statement":"The recombinant COASY DPCK domain carrying p.Arg499Cys did not produce a detectable CoA HPLC peak, whereas wild-type DPCK converted dephospho-CoA to CoA.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"b689e70b-9f6a-5539-8eaa-0f2a2e829ae6","mechanism_event_label":"This COASY variant disabled the final reaction in the isolated-enzyme test.","subject":{"id":"3a6391f7-e62e-5662-84c2-5dfe294e18bd","slug":"coasy-r499c","display_name":"Human COASY p.Arg499Cys protein","entity_type_key":"protein_state"},"object":{"id":"9bc4f783-5bbd-51de-b3b1-15b6fa910121","slug":"dephospho-coa","display_name":"3′-Dephospho-coenzyme A","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"b689e70b-9f6a-5539-8eaa-0f2a2e829ae6","stable_key":"f992b796-377d-53bf-a39b-7e5d41dbe194:b5-bio-coasy-r499c-activity-event","event_type":"biochemical_relationship","label":"This COASY variant disabled the final reaction in the isolated-enzyme test.","description":"The recombinant COASY DPCK domain carrying p.Arg499Cys did not produce a detectable CoA HPLC peak, whereas wild-type DPCK converted dephospho-CoA to CoA.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"485e7221-d4ad-55fc-a7f2-28caa0d05066","slug":"coasy","display_name":"Coenzyme A synthase / COASY","entity_type_key":"protein"},"role":"wild_type_comparator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"58b974f1-d389-5bf6-81cd-889c44442c42","slug":"atp","display_name":"ATP","entity_type_key":"small_molecule"},"role":"cosubstrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"4faa6456-aff8-59eb-9e3f-3326a436e401","slug":"coenzyme-a","display_name":"Coenzyme A","entity_type_key":"small_molecule"},"role":"assayed_product","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"3a6391f7-e62e-5662-84c2-5dfe294e18bd","slug":"coasy-r499c","display_name":"Human COASY p.Arg499Cys protein","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"9bc4f783-5bbd-51de-b3b1-15b6fa910121","slug":"dephospho-coa","display_name":"3′-Dephospho-coenzyme A","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Two unrelated human NBIA cases, primary fibroblasts, recombinant wild-type and variant COASY DPCK domains and yeast studies","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"HPLC assays with 1 microgram recombinant wild-type or p.Arg499Cys DPCK protein, ATP and dephospho-CoA; substrate concentrations not extracted.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Loss of detectable isolated-domain activity does not mean that every patient cell has no CoA. Wild-type and variant domains were recombinantly produced in bacteria.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"pantothenate","display_name":"Pantothenate (vitamin B5)","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"This COASY variant disabled the final reaction in the isolated-enzyme test.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b5-bio-coasy2014] Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation. (2014). https://pubmed.ncbi.nlm.nih.gov/24360804/ DOI: 10.1016/j.ajhg.2013.11.008","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},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"2eecb69f-7dd0-5bd9-8807-9de0f96ea575","evidence_kind":"source_excerpt","locator":"Lines 730-741","start_line":730,"end_line":741,"excerpt":"### b5-bio-coasy-r499c-activity\nThe recombinant COASY DPCK domain carrying p.Arg499Cys did not produce a detectable CoA HPLC peak, whereas wild-type DPCK converted dephospho-CoA to CoA.\nCondition category: machinery_impairment\nnutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This COASY variant disabled the final reaction in the isolated-enzyme test.\norganism: Homo sapiens\ntissue_or_cell_type: Purified recombinant protein; no intact tissue\nexperimental_model: Two unrelated human NBIA cases, primary fibroblasts, recombinant wild-type and variant COASY DPCK domains and yeast studies\nlimitations: Loss of detectable isolated-domain activity does not mean that every patient cell has no CoA. Wild-type and variant domains were recombinantly produced in bacteria.\nexposure: HPLC assays with 1 microgram recombinant wild-type or p.Arg499Cys DPCK protein, ATP and dephospho-CoA; substrate concentrations not extracted.\ncross_nutrient: false\n[b5-bio-coasy2014] Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation. (2014). https://pubmed.ncbi.nlm.nih.gov/24360804/ DOI: 10.1016/j.ajhg.2013.11.008","model_system":"Two unrelated human NBIA cases, primary fibroblasts, recombinant wild-type and variant COASY DPCK domains and yeast studies","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b5-bio-coasy2014] Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation. (2014). https://pubmed.ncbi.nlm.nih.gov/24360804/ DOI: 10.1016/j.ajhg.2013.11.008","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"0716b500-dd0b-5425-b9d0-d88bc9c09e86","stable_key":"import-f992b796-377d-53bf-a39b-7e5d41dbe194","title":"Pantothenic acid (vitamin B5): coenzyme A, 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":"b5a49f5a2373ca6064c9a4e014e052dad2f6f199a82bb09b26b82b831c36110b","revision_id":"78f3e793-f084-5ee2-8703-b661c4b650bf","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}