{"id":"9e6687eb-d8f8-5430-8f6d-928ded205473","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-transport-alpl-impaired","predicate":"reduces-activity-of","statement":"Hypophosphatasia fibroblasts retained only 2-5% of control phosphatase activity toward PLP and other tested substrates.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"cc16a9c2-b281-5260-becb-8447628471e3","mechanism_event_label":"A handling defect limits extracellular PLP processing.","subject":{"id":"f7dd2a90-dc95-5a49-9a46-96c957f6aa9b","slug":"human-alpl-hypophosphatasia-genotypes","display_name":"Human hypophosphatasia ALPL impairment","entity_type_key":"gene"},"object":{"id":"3148c377-9b4c-56ca-bc36-081bf1905d57","slug":"alpl","display_name":"Tissue-nonspecific alkaline phosphatase ALPL / TNAP","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"cc16a9c2-b281-5260-becb-8447628471e3","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-transport-alpl-impaired-event","event_type":"biochemical_relationship","label":"A handling defect limits extracellular PLP processing.","description":"Hypophosphatasia fibroblasts retained only 2-5% of control phosphatase activity toward PLP and other tested substrates.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6b656ff5-9532-5da4-8eea-8ca163a48649","slug":"pyridoxal-phosphate","display_name":"PLP","entity_type_key":"small_molecule"},"role":"natural substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f7dd2a90-dc95-5a49-9a46-96c957f6aa9b","slug":"human-alpl-hypophosphatasia-genotypes","display_name":"Human hypophosphatasia ALPL impairment","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"3148c377-9b4c-56ca-bc36-081bf1905d57","slug":"alpl","display_name":"Tissue-nonspecific alkaline phosphatase ALPL / TNAP","entity_type_key":"protein"},"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: intact/disrupted cells, PI-PLC and patient enzyme activity","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Normal and hypophosphatasia human skin fibroblasts.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Patient versus control fibroblast enzyme assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Not an intake-deficiency experiment.","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 handling defect limits extracellular PLP processing.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[fedde1990] Alkaline phosphatase (tissue-nonspecific isoenzyme) is a phosphoethanolamine and pyridoxal-5'-phosphate ectophosphatase: normal and hypophosphatasia fibroblast study. (1990). https://pubmed.ncbi.nlm.nih.gov/2220817/","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Skin fibroblasts","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":"ed979c5a-fe42-558d-88e1-238d8933f24c","evidence_kind":"source_excerpt","locator":"Lines 322-333","start_line":322,"end_line":333,"excerpt":"### b6-transport-alpl-impaired\nHypophosphatasia fibroblasts retained only 2-5% of control phosphatase activity toward PLP and other tested substrates.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A handling defect limits extracellular PLP processing.\norganism: Homo sapiens\ntissue_or_cell_type: Skin fibroblasts\nexperimental_model: Normal and hypophosphatasia human skin fibroblasts.\nlimitations: Not an intake-deficiency experiment.\nexposure: Patient versus control fibroblast enzyme assays.\nevidence_location: Indexed abstract: intact/disrupted cells, PI-PLC and patient enzyme activity\n[fedde1990] Alkaline phosphatase (tissue-nonspecific isoenzyme) is a phosphoethanolamine and pyridoxal-5'-phosphate ectophosphatase: normal and hypophosphatasia fibroblast study. (1990). https://pubmed.ncbi.nlm.nih.gov/2220817/","model_system":"Normal and hypophosphatasia human skin fibroblasts.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [fedde1990] Alkaline phosphatase (tissue-nonspecific isoenzyme) is a phosphoethanolamine and pyridoxal-5'-phosphate ectophosphatase: normal and hypophosphatasia fibroblast study. (1990). https://pubmed.ncbi.nlm.nih.gov/2220817/","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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