{"id":"e0d7b9b7-abc5-511e-9f0c-2a4a3596451b","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:mg-alpl-high-calcium-zinc-displacement","predicate":"at_high_concentration_inhibits","statement":"Very high calcium displaced or competed with Zn at TNAP M1/M2 sites and reduced activity; concentrations depended on pH.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"d7db07d9-f076-579d-9e38-83c6472e880b","mechanism_event_label":"The same calcium ion can activate one site and interfere with another.","subject":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"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":"d7db07d9-f076-579d-9e38-83c6472e880b","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:mg-alpl-high-calcium-zinc-displacement-event","event_type":"biochemical_relationship","label":"The same calcium ion can activate one site and interfere with another.","description":"Very high calcium displaced or competed with Zn at TNAP M1/M2 sites and reduced activity; concentrations depended on pH.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"bff427ab-35f9-59c2-bb24-fd5953bbaec2","slug":"magnesium-ion","display_name":"Mg2+","entity_type_key":"ion"},"role":"M3_site_context","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"role":"competed_metal","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"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":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Calcium/Zn/Mg interaction depends on site occupancy and local conditions.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified TNAP concentration/pH experiment. Activity was measured using artificial pNPP substrate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Local experimental concentrations cannot be converted to dietary dose cutoffs. This assay does not quantify physiological pyrophosphate turnover or mineral deposition.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Magnesium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"magnesium","display_name":"Magnesium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The same calcium ion can activate one site and interfere with another.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Recombinant human TNAP; cell-free p-nitrophenyl phosphate (pNPP) hydrolysis assay","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"2222952b-214e-547a-8d10-f5da12b624df","evidence_kind":"source_excerpt","locator":"Lines 1491-1501","start_line":1491,"end_line":1501,"excerpt":"### mg-alpl-high-calcium-zinc-displacement\nVery high calcium displaced or competed with Zn at TNAP M1/M2 sites and reduced activity; concentrations depended on pH.\nCondition category: normal\nnutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The same calcium ion can activate one site and interfere with another.\norganism: Homo sapiens\ntissue_or_cell_type: Recombinant human TNAP; cell-free p-nitrophenyl phosphate (pNPP) hydrolysis assay\nexperimental_model: Purified TNAP concentration/pH experiment. Activity was measured using artificial pNPP substrate.\nlimitations: Local experimental concentrations cannot be converted to dietary dose cutoffs. This assay does not quantify physiological pyrophosphate turnover or mineral deposition.\ncross_nutrient: Calcium/Zn/Mg interaction depends on site occupancy and local conditions.\n[mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874","model_system":"Purified TNAP concentration/pH experiment. Activity was measured using artificial pNPP substrate.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"dd101e28-1a2e-5a48-9d1e-809c77514866","stable_key":"import-0f17db03-207f-5910-ac8e-13dfc2f378ce","title":"Magnesium: cross-nutrient mechanisms and deficiency (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":"e111c412f57143a17e8e65e74e8f7888b5bb9a61099873f4767f527fac19bb07","revision_id":"6b7f04f2-66ed-5859-955f-c2b50d4bf041","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}