{"id":"00aa6eac-0472-50f3-ad7f-856c9e2af993","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:alpl-pyrophosphate-hydrolysis","predicate":"hydrolyzed_to","statement":"ALPL/TNAP hydrolyzes extracellular pyrophosphate to inorganic phosphate, reducing an inhibitor of matrix mineralization.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"46da876c-01db-5d79-b28c-658913ad7dab","mechanism_event_label":"TNAP removes a local brake on calcium phosphate crystal growth.","subject":{"id":"cd026fef-529f-5e03-b6b5-37ede8ce9127","slug":"pyrophosphate","display_name":"Inorganic pyrophosphate","entity_type_key":"small_molecule"},"object":{"id":"ee63fe8e-92f3-552f-8049-a5f1fa1e1523","slug":"phosphate-ion","display_name":"Inorganic phosphate (Pi; protonation depends on pH)","entity_type_key":"ion"},"evidence_count":1,"mechanism_event":{"id":"46da876c-01db-5d79-b28c-658913ad7dab","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:alpl-pyrophosphate-hydrolysis-event","event_type":"biochemical_relationship","label":"TNAP removes a local brake on calcium phosphate crystal growth.","description":"ALPL/TNAP hydrolyzes extracellular pyrophosphate to inorganic phosphate, reducing an inhibitor of matrix mineralization.","status":"provisional","compartment":{"slug":"bone-extracellular-matrix","display_name":"Bone extracellular matrix"},"participants":[{"entity":{"id":"3148c377-9b4c-56ca-bc36-081bf1905d57","slug":"alpl","display_name":"Tissue-nonspecific alkaline phosphatase ALPL / TNAP","entity_type_key":"protein"},"role":"catalyst","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"cd026fef-529f-5e03-b6b5-37ede8ce9127","slug":"pyrophosphate","display_name":"Inorganic pyrophosphate","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"d31225b7-8e94-5857-9ea1-67ac794b1f15","slug":"water","display_name":"H2O","entity_type_key":"small_molecule"},"role":"hydrolysis_cosubstrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"ee63fe8e-92f3-552f-8049-a5f1fa1e1523","slug":"phosphate-ion","display_name":"Inorganic phosphate (Pi; 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this is not evidence that calcium activates TNAP.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Calcium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"calcium","display_name":"Calcium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"TNAP removes a local brake on calcium phosphate crystal growth.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[hessle2002] Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization (2002). https://pmc.ncbi.nlm.nih.gov/articles/PMC123160/ DOI: 10.1073/pnas.142063399","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Osteoblast matrix and matrix vesicles","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"6677cb0a-2a7b-52bc-9a53-68c32457cc22","evidence_kind":"source_excerpt","locator":"Lines 931-941","start_line":931,"end_line":941,"excerpt":"### alpl-pyrophosphate-hydrolysis\nALPL/TNAP hydrolyzes extracellular pyrophosphate to inorganic phosphate, reducing an inhibitor of matrix mineralization.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: TNAP removes a local brake on calcium phosphate crystal growth.\norganism: Mus musculus\ntissue_or_cell_type: Osteoblast matrix and matrix vesicles\nexperimental_model: Genetic and ex vivo pyrophosphate/mineralization experiments\nlimitations: Pi and PPi labels pool protonation states; this is not evidence that calcium activates TNAP.\ncompartment_description: Extracellular matrix and vesicle surface\n[hessle2002] Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization (2002). https://pmc.ncbi.nlm.nih.gov/articles/PMC123160/ DOI: 10.1073/pnas.142063399","model_system":"Genetic and ex vivo pyrophosphate/mineralization experiments","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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