{"id":"502d6d5d-d38c-50fa-a043-c12f25f4ed15","stable_key":"f992b796-377d-53bf-a39b-7e5d41dbe194:b5-bio-pank4-flux-suppression","predicate":"suppresses","statement":"Re-expression of active PANK4 in PANK4-knockout AKT p.E17K/+ MCF10A cells suppressed newly synthesized CoA, whereas phosphatase-inactive mutants did not reproduce the suppression.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"b3981aad-7d19-59b8-87b4-235a7cd3d042","mechanism_event_label":"PANK4 phosphatase activity can reduce new CoA production in cultured cells.","subject":{"id":"19aa4674-db27-50f2-a232-44e427da4a5a","slug":"pank4","display_name":"Human pantothenate kinase 4 / PANK4","entity_type_key":"protein"},"object":{"id":"acaab13e-2d2f-5305-b49f-e621ecbfa402","slug":"cellular-coa-biosynthesis","display_name":"Cellular de novo coenzyme A synthesis","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"b3981aad-7d19-59b8-87b4-235a7cd3d042","stable_key":"f992b796-377d-53bf-a39b-7e5d41dbe194:b5-bio-pank4-flux-suppression-event","event_type":"biochemical_relationship","label":"PANK4 phosphatase activity can reduce new CoA production in cultured cells.","description":"Re-expression of active PANK4 in PANK4-knockout AKT p.E17K/+ MCF10A cells suppressed newly synthesized CoA, whereas phosphatase-inactive mutants did not reproduce the suppression.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"7bc62072-9517-5563-a3b8-8c5ab64a464b","slug":"pantothenate","display_name":"Pantothenate (vitamin B5)","entity_type_key":"small_molecule"},"role":"isotope_tracer_precursor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"4faa6456-aff8-59eb-9e3f-3326a436e401","slug":"coenzyme-a","display_name":"Coenzyme A","entity_type_key":"small_molecule"},"role":"synthesis_product","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"aab78666-4f68-5db2-b86e-a3c6b18ed62d","slug":"phosphopantetheine","display_name":"4′-Phosphopantetheine","entity_type_key":"small_molecule"},"role":"phosphatase_target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"19aa4674-db27-50f2-a232-44e427da4a5a","slug":"pank4","display_name":"Human pantothenate kinase 4 / PANK4","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"acaab13e-2d2f-5305-b49f-e621ecbfa402","slug":"cellular-coa-biosynthesis","display_name":"Cellular de novo coenzyme A synthesis","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human cultured-cell metabolomics and isotope tracing, PANK4 editing/re-expression and immunopurified human PANK4 phosphatase assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Wild-type versus D623A or D659A PANK4 re-expression; 3-hour carbon-13/nitrogen-15 vitamin-B5 labelling with growth factors.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Engineered cellular PI3K–AKT context; isotope concentration not verified. No claim that PANK4 controls every tissue or that dietary B5 produces the same response.","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":"PANK4 phosphatase activity can reduce new CoA production in cultured cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b5-bio-dibble2022] PI3K drives the de novo synthesis of coenzyme A from vitamin B5. (2022). https://pubmed.ncbi.nlm.nih.gov/35896750/ DOI: 10.1038/s41586-022-04984-8","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Human MCF10A mammary epithelial cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"52b09679-7634-59cb-a252-bf68d80ac9ef","evidence_kind":"source_excerpt","locator":"Lines 678-689","start_line":678,"end_line":689,"excerpt":"### b5-bio-pank4-flux-suppression\nRe-expression of active PANK4 in PANK4-knockout AKT p.E17K/+ MCF10A cells suppressed newly synthesized CoA, whereas phosphatase-inactive mutants did not reproduce the suppression.\nCondition category: normal\nnutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: PANK4 phosphatase activity can reduce new CoA production in cultured cells.\norganism: Homo sapiens\ntissue_or_cell_type: Human MCF10A mammary epithelial cells\nexperimental_model: Human cultured-cell metabolomics and isotope tracing, PANK4 editing/re-expression and immunopurified human PANK4 phosphatase assays\nlimitations: Engineered cellular PI3K–AKT context; isotope concentration not verified. No claim that PANK4 controls every tissue or that dietary B5 produces the same response.\nexposure: Wild-type versus D623A or D659A PANK4 re-expression; 3-hour carbon-13/nitrogen-15 vitamin-B5 labelling with growth factors.\ncross_nutrient: false\n[b5-bio-dibble2022] PI3K drives the de novo synthesis of coenzyme A from vitamin B5. (2022). https://pubmed.ncbi.nlm.nih.gov/35896750/ DOI: 10.1038/s41586-022-04984-8","model_system":"Human cultured-cell metabolomics and isotope tracing, PANK4 editing/re-expression and immunopurified human PANK4 phosphatase assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b5-bio-dibble2022] PI3K drives the de novo synthesis of coenzyme A from vitamin B5. (2022). https://pubmed.ncbi.nlm.nih.gov/35896750/ DOI: 10.1038/s41586-022-04984-8","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}