{"id":"e344a1b3-014f-5883-aec6-4d025369268b","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-transport-plpbp-fibroblast-accumulation","predicate":"increases","statement":"PLPBP-deficient patient fibroblasts in Darin 2016 accumulated approximately two- to threefold more PLP than controls in the tested culture medium.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"25ef1755-756b-5a93-9d44-6c7e33d7e422","mechanism_event_label":"A cellular handling defect can raise the measured PLP pool.","subject":{"id":"9fcb1a6d-17ec-5677-bbbe-0bac9808095c","slug":"human-plpbp-biallelic-loss-of-function","display_name":"Human biallelic PLPBP impairment","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":"25ef1755-756b-5a93-9d44-6c7e33d7e422","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-transport-plpbp-fibroblast-accumulation-event","event_type":"biochemical_relationship","label":"A cellular handling defect can raise the measured PLP pool.","description":"PLPBP-deficient patient fibroblasts in Darin 2016 accumulated approximately two- to threefold more PLP than controls in the tested culture medium.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"095f4f11-a415-519e-a0e2-d68cb617f397","slug":"plpbp","display_name":"Human PLP-binding protein / PLPBP","entity_type_key":"protein"},"role":"impaired protein","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9fcb1a6d-17ec-5677-bbbe-0bac9808095c","slug":"human-plpbp-biallelic-loss-of-function","display_name":"Human biallelic PLPBP impairment","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"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":2,"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":"Indexed abstract; full-text discussion of cultured patient fibroblasts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Patient fibroblasts and biochemical studies in vitamin-B6-dependent epilepsy.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Patient cells cultured in normal medium containing serum and pyridoxine.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Later different cultures showed lower PLP; bulk PLP is not enzyme-specific cofactor availability.","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":"A cellular handling defect can raise the measured PLP pool.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[darin2016] Mutations in PROSC Disrupt Cellular Pyridoxal Phosphate Homeostasis and Cause Vitamin-B6-Dependent Epilepsy. 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