{"id":"4aef8709-23c4-5eaf-8670-b941eb3c1005","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:low-mg-galpha-exchange-explains-paradox","predicate":"restrains","statement":"Reconstituted G-protein assays supported Mg-dependent restraint of Galpha nucleotide exchange; reduced Mg enhanced signaling associated with basal CaSR activity.","claim_class":"hypothesis_link","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"554ffd43-62f7-5dbe-a6d4-2bb45fa47cab","mechanism_event_label":"Less Mg can loosen the restraint on the G-protein switch, allowing the receptor pathway to suppress PTH more strongly.","subject":{"id":"bff427ab-35f9-59c2-bb24-fd5953bbaec2","slug":"magnesium-ion","display_name":"Mg2+","entity_type_key":"ion"},"object":{"id":"9c9409b9-1a55-5d15-afdb-52314c9082a7","slug":"g-alpha-nucleotide-exchange","display_name":"G protein alpha guanine-nucleotide exchange","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"554ffd43-62f7-5dbe-a6d4-2bb45fa47cab","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:low-mg-galpha-exchange-explains-paradox-event","event_type":"biochemical_relationship","label":"Less Mg can loosen the restraint on the G-protein switch, allowing the receptor pathway to suppress PTH more strongly.","description":"Reconstituted G-protein assays supported Mg-dependent restraint of Galpha nucleotide exchange; reduced Mg enhanced signaling associated with basal CaSR activity.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"1c0d5c58-d358-5501-9bdf-8999bcf79fd4","slug":"casr","display_name":"Calcium-sensing receptor / CaSR","entity_type_key":"protein"},"role":"basally active receptor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"c8ee3465-3054-5b36-ba07-79cb46bd8ec9","slug":"gnai1","display_name":"G protein alpha-i1 subunit / GNAI1","entity_type_key":"protein"},"role":"signaling switch","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"f30bc32c-5319-5d92-a856-135b64d4d043","slug":"gdp","display_name":"Guanosine diphosphate","entity_type_key":"small_molecule"},"role":"released nucleotide","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"bf7dccfe-8518-5e49-aa95-5cface204ec1","slug":"gtp-gamma-s","display_name":"Guanosine 5-prime-O-(3-thiotriphosphate)","entity_type_key":"small_molecule"},"role":"activation assay ligand","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"bff427ab-35f9-59c2-bb24-fd5953bbaec2","slug":"magnesium-ion","display_name":"Mg2+","entity_type_key":"ion"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"9c9409b9-1a55-5d15-afdb-52314c9082a7","slug":"g-alpha-nucleotide-exchange","display_name":"G protein alpha guanine-nucleotide exchange","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; 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unverified.","entity":null}],"evidence":[{"id":"37af685d-820b-508a-842e-d42a3c51cc56","evidence_kind":"source_excerpt","locator":"Lines 457-467","start_line":457,"end_line":467,"excerpt":"### low-mg-galpha-exchange-explains-paradox\nReconstituted G-protein assays supported Mg-dependent restraint of Galpha nucleotide exchange; reduced Mg enhanced signaling associated with basal CaSR activity.\nCondition category: nutrient_deficiency\nnutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Less Mg can loosen the restraint on the G-protein switch, allowing the receptor pathway to suppress PTH more strongly.\norganism: Human receptor-expression system with purified/recombinant G proteins\ntissue_or_cell_type: Reconstituted membrane signaling system\nexperimental_model: CaSR-expressing HEK-293 membranes reconstituted with G proteins\nlimitations: Mechanistic explanation supported by probes; not an established sole cause of human hypomagnesemic hypocalcemia.\ncross_nutrient: magnesium -> CaSR/PTH -> calcium\n[quitterer-2001-magnesium-paradox] Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits (2001). https://pubmed.ncbi.nlm.nih.gov/11102444/ DOI: 10.1074/jbc.M007727200","model_system":"CaSR-expressing HEK-293 membranes reconstituted with G proteins","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [quitterer-2001-magnesium-paradox] Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits (2001). https://pubmed.ncbi.nlm.nih.gov/11102444/ DOI: 10.1074/jbc.M007727200","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}