{"id":"f90b4b5b-8324-598a-af30-46ab5c150e1d","stable_key":"f992b796-377d-53bf-a39b-7e5d41dbe194:b5-bio-pank2-model-complex-i-rescue","predicate":"restores_in_model","statement":"Oral 4′-phosphopantetheine corrected the complex I activity defect in globus-pallidus-enriched brain tissue from Pank2-null mice.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"82347f56-1ae2-5f10-9df9-0ecb1e8bca38","mechanism_event_label":"A downstream intermediate improved a mitochondrial enzyme measurement in this genetic mouse model.","subject":{"id":"aab78666-4f68-5db2-b86e-a3c6b18ed62d","slug":"phosphopantetheine","display_name":"4′-Phosphopantetheine","entity_type_key":"small_molecule"},"object":{"id":"153f1c0b-d5c1-5e57-93d7-2f33bfc14493","slug":"pank2-mouse-brain-complex-i-activity","display_name":"Mitochondrial complex I activity in Pank2-mutant mouse brain","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"82347f56-1ae2-5f10-9df9-0ecb1e8bca38","stable_key":"f992b796-377d-53bf-a39b-7e5d41dbe194:b5-bio-pank2-model-complex-i-rescue-event","event_type":"biochemical_relationship","label":"A downstream intermediate improved a mitochondrial enzyme measurement in this genetic mouse model.","description":"Oral 4′-phosphopantetheine corrected the complex I activity defect in globus-pallidus-enriched brain tissue from Pank2-null mice.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3a8b4e61-4772-53f4-9a80-0d4071f12561","slug":"mouse-pank2-null-genotype","display_name":"Mouse Pank2 loss-of-function genotype","entity_type_key":"gene"},"role":"impaired_machinery","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":"pathway_context","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":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"153f1c0b-d5c1-5e57-93d7-2f33bfc14493","slug":"pank2-mouse-brain-complex-i-activity","display_name":"Mitochondrial complex I activity in Pank2-mutant mouse brain","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"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":"C57/BL6 Pank2-null mice, both sexes aged 3–6 months, with globus-pallidus-enriched brain dissection; human PKAN cell experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Oral 4′-phosphopantetheine in 10% sucrose for 14 days; efficacy regimen 5 micrograms/g body weight (5 mg/kg); both-sex Pank2-null C57/BL6 mice aged 3–6 months; Fig. 2E n=5 per genotype/treatment group.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Biochemical rescue in mice, not a human efficacy result or proof of intact blood–brain-barrier delivery. The tissue was GP-enriched, not purified GP. Loss of Pank2 is machinery impairment, not dietary B5 withdrawal.","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":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A downstream intermediate improved a mitochondrial enzyme measurement in this genetic mouse model.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b5-bio-salvage2019] 4'-Phosphopantetheine corrects CoA, iron, and dopamine metabolic defects in mammalian models of PKAN. (2019). https://pubmed.ncbi.nlm.nih.gov/31660701/ DOI: 10.15252/emmm.201910489","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Globus-pallidus-enriched brain region; crude dissection also included neighboring structures","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":"a615874e-3aae-5f88-9268-c07880d25a06","evidence_kind":"source_excerpt","locator":"Lines 782-793","start_line":782,"end_line":793,"excerpt":"### b5-bio-pank2-model-complex-i-rescue\nOral 4′-phosphopantetheine corrected the complex I activity defect in globus-pallidus-enriched brain tissue from Pank2-null mice.\nCondition category: machinery_impairment\nnutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A downstream intermediate improved a mitochondrial enzyme measurement in this genetic mouse model.\norganism: Mus musculus\ntissue_or_cell_type: Globus-pallidus-enriched brain region; crude dissection also included neighboring structures\nexperimental_model: C57/BL6 Pank2-null mice, both sexes aged 3–6 months, with globus-pallidus-enriched brain dissection; human PKAN cell experiments\nlimitations: Biochemical rescue in mice, not a human efficacy result or proof of intact blood–brain-barrier delivery. The tissue was GP-enriched, not purified GP. Loss of Pank2 is machinery impairment, not dietary B5 withdrawal.\nexposure: Oral 4′-phosphopantetheine in 10% sucrose for 14 days; efficacy regimen 5 micrograms/g body weight (5 mg/kg); both-sex Pank2-null C57/BL6 mice aged 3–6 months; Fig. 2E n=5 per genotype/treatment group.\ncross_nutrient: false\n[b5-bio-salvage2019] 4'-Phosphopantetheine corrects CoA, iron, and dopamine metabolic defects in mammalian models of PKAN. (2019). https://pubmed.ncbi.nlm.nih.gov/31660701/ DOI: 10.15252/emmm.201910489","model_system":"C57/BL6 Pank2-null mice, both sexes aged 3–6 months, with globus-pallidus-enriched brain dissection; human PKAN cell experiments","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b5-bio-salvage2019] 4'-Phosphopantetheine corrects CoA, iron, and dopamine metabolic defects in mammalian models of PKAN. (2019). https://pubmed.ncbi.nlm.nih.gov/31660701/ DOI: 10.15252/emmm.201910489","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}