{"id":"59155bae-9c2a-5218-b161-27b0ce5dbf5c","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-transport-slc25a38-tracer","predicate":"impairs-accumulation-of","statement":"After a 100 nM D3-PN pulse, labeled PLP appeared in whole cells but scarcely in SLC25A38-null mitochondria.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"ea16164b-7fee-55c2-ad4c-b4b27bd8c5a4","mechanism_event_label":"Synthesis persisted while mitochondrial accumulation failed.","subject":{"id":"ef2b6140-11ac-5633-9af3-c2aab23ccc89","slug":"human-slc25a38-knockout","display_name":"Human SLC25A38 knockout genotype","entity_type_key":"gene"},"object":{"id":"6b656ff5-9532-5da4-8eea-8ca163a48649","slug":"pyridoxal-phosphate","display_name":"PLP","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"ea16164b-7fee-55c2-ad4c-b4b27bd8c5a4","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-transport-slc25a38-tracer-event","event_type":"biochemical_relationship","label":"Synthesis persisted while mitochondrial accumulation failed.","description":"After a 100 nM D3-PN pulse, labeled PLP appeared in whole cells but scarcely in SLC25A38-null mitochondria.","status":"provisional","compartment":{"slug":"mitochondria","display_name":"Mitochondria"},"participants":[{"entity":{"id":"aa6648f2-8962-5567-9939-ef4145e40ed1","slug":"pyridoxine","display_name":"Pyridoxine","entity_type_key":"small_molecule"},"role":"isotopically labeled precursor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d2d46db7-13a4-595f-adaa-70ad6ca31a6c","slug":"pdxk","display_name":"Pyridoxal kinase / PDXK","entity_type_key":"protein"},"role":"activation enzyme","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a01d08b9-a749-5bc3-934b-af0b35024b54","slug":"pnpo","display_name":"Pyridoxine 5-prime-phosphate oxidase / PNPO","entity_type_key":"protein"},"role":"activation enzyme","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"ef2b6140-11ac-5633-9af3-c2aab23ccc89","slug":"human-slc25a38-knockout","display_name":"Human SLC25A38 knockout genotype","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"6b656ff5-9532-5da4-8eea-8ca163a48649","slug":"pyridoxal-phosphate","display_name":"PLP","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":"evidence_location","value_text":"Figure 4A-B","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"100 nM D3-PN, one-hour tracing after 10 nM PN conditioning.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Import, retention and indirect regulation remain alternatives.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-b6","display_name":"Vitamin B6","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Synthesis persisted while mitochondrial accumulation failed.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[pena2025] SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. (2025). https://pubmed.ncbi.nlm.nih.gov/39856062/ DOI: 10.1038/s41467-025-56130-3","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"K562 cells","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":"b00154e4-bbe3-5047-921f-d5abd4cd2ea3","evidence_kind":"source_excerpt","locator":"Lines 465-476","start_line":465,"end_line":476,"excerpt":"### b6-transport-slc25a38-tracer\nAfter a 100 nM D3-PN pulse, labeled PLP appeared in whole cells but scarcely in SLC25A38-null mitochondria.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Synthesis persisted while mitochondrial accumulation failed.\norganism: Homo sapiens\ntissue_or_cell_type: K562 cells\nexperimental_model: Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing.\nlimitations: Import, retention and indirect regulation remain alternatives.\nexposure: 100 nM D3-PN, one-hour tracing after 10 nM PN conditioning.\nevidence_location: Figure 4A-B\n[pena2025] SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. (2025). https://pubmed.ncbi.nlm.nih.gov/39856062/ DOI: 10.1038/s41467-025-56130-3","model_system":"Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [pena2025] SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. (2025). https://pubmed.ncbi.nlm.nih.gov/39856062/ DOI: 10.1038/s41467-025-56130-3","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"251773bb-16f5-5903-b135-db4a61d9dec4","stable_key":"import-1310afbd-6010-586e-805d-551d846da421","title":"Vitamin B6: mechanisms, 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. 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