{"id":"f8fa184d-600d-5c41-9669-d2190c28e09b","stable_key":"f992b796-377d-53bf-a39b-7e5d41dbe194:b5-bio-akt-pank4-regulation","predicate":"relieves_suppression_by_phosphorylating","statement":"AKT phosphorylation of PANK4 relieved its suppression of de novo CoA synthesis in the study models.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"447393b6-bef4-540e-88c4-6016bfea7d32","mechanism_event_label":"Growth-factor signalling can ease the PANK4 brake on CoA production.","subject":{"id":"a13cb592-c939-5f92-9206-d774248802fc","slug":"akt-proteins","display_name":"AKT serine/threonine kinase family","entity_type_key":"protein_family"},"object":{"id":"19aa4674-db27-50f2-a232-44e427da4a5a","slug":"pank4","display_name":"Human pantothenate kinase 4 / PANK4","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"447393b6-bef4-540e-88c4-6016bfea7d32","stable_key":"f992b796-377d-53bf-a39b-7e5d41dbe194:b5-bio-akt-pank4-regulation-event","event_type":"biochemical_relationship","label":"Growth-factor signalling can ease the PANK4 brake on CoA production.","description":"AKT phosphorylation of PANK4 relieved its suppression of de novo CoA synthesis in the study models.","status":"provisional","compartment":null,"participants":[{"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":"regulated_process","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"7bc62072-9517-5563-a3b8-8c5ab64a464b","slug":"pantothenate","display_name":"Pantothenate (vitamin B5)","entity_type_key":"small_molecule"},"role":"biosynthetic_precursor","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":"product","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"a13cb592-c939-5f92-9206-d774248802fc","slug":"akt-proteins","display_name":"AKT serine/threonine kinase family","entity_type_key":"protein_family"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"19aa4674-db27-50f2-a232-44e427da4a5a","slug":"pank4","display_name":"Human pantothenate kinase 4 / PANK4","entity_type_key":"protein"},"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":"PI3K–AKT signalling and PANK4 phosphorylation manipulations; no nutrient dosing trial.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Primary abstract with supporting cellular assays; mechanism is not a rationale for treating insulin signalling or increasing B5 intake.","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":"Growth-factor signalling can ease the PANK4 brake on CoA production.","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 cultured-cell models","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"84b05915-100f-5122-9834-5986fb52b280","evidence_kind":"source_excerpt","locator":"Lines 691-702","start_line":691,"end_line":702,"excerpt":"### b5-bio-akt-pank4-regulation\nAKT phosphorylation of PANK4 relieved its suppression of de novo CoA synthesis in the study models.\nCondition category: normal\nnutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Growth-factor signalling can ease the PANK4 brake on CoA production.\norganism: Homo sapiens\ntissue_or_cell_type: Human cultured-cell models\nexperimental_model: Human cultured-cell metabolomics and isotope tracing, PANK4 editing/re-expression and immunopurified human PANK4 phosphatase assays\nlimitations: Primary abstract with supporting cellular assays; mechanism is not a rationale for treating insulin signalling or increasing B5 intake.\nexposure: PI3K–AKT signalling and PANK4 phosphorylation manipulations; no nutrient dosing trial.\ncross_nutrient: false\n[b5-bio-dibble2022] PI3K drives the de novo synthesis of coenzyme A from vitamin B5. 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