{"id":"dcd23b49-ec1a-5a52-80ba-c387e9464948","stable_key":"a9828b14-fbd7-57bf-9e01-0d52d1b42a1f:citrulline-calcium-nos","predicate":"regulates","statement":"The calcium ionophore A23187 increased arginine-to-citrulline conversion in cells expressing human endothelial NOS.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"175be3cf-ac3b-5f17-a412-ea9b9d66b005","mechanism_event_label":"Calcium signaling can activate this enzyme; this experiment did not test taking calcium tablets.","subject":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"object":{"id":"5e0c46ae-303d-51a2-aa1a-248d36fa7c70","slug":"human-enos-catalytic-activity","display_name":"Human eNOS catalytic activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"175be3cf-ac3b-5f17-a412-ea9b9d66b005","stable_key":"a9828b14-fbd7-57bf-9e01-0d52d1b42a1f:citrulline-calcium-nos-event","event_type":"biochemical_relationship","label":"Calcium signaling can activate this enzyme; this experiment did not test taking calcium tablets.","description":"The calcium ionophore A23187 increased arginine-to-citrulline conversion in cells expressing human endothelial NOS.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"8a9c57f6-eafd-5243-afaf-d4e830939c4b","slug":"nos3","display_name":"Human endothelial nitric oxide synthase / eNOS / NOS3","entity_type_key":"protein"},"role":"enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"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":1,"notes":""},{"entity":{"id":"5e0c46ae-303d-51a2-aa1a-248d36fa7c70","slug":"human-enos-catalytic-activity","display_name":"Human eNOS catalytic activity","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/citrulline-research/1378832.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"265be186f6d8172b272e7b1e75b4fbae12a6df78c7396cad499bce2b195b1206\", \"start_char\": 0, \"end_char\": 1652, \"text_sha256\": \"265be186f6d8172b272e7b1e75b4fbae12a6df78c7396cad499bce2b195b1206\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Functional expression and reporter-cell coculture","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"NOS3 transfection and calcium ionophore A23187","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Heterologous expression; reporter activation supports bioactive NO production, not a clinical calcium supplementation effect.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Citrulline research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"citrulline","display_name":"L-Citrulline","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human NOS3 expressed in NIH3T3 cells; rat reporter fibroblasts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Calcium signaling can activate this enzyme; this experiment did not test taking calcium tablets.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[citrulline-p1378832] Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase. (1992). https://pubmed.ncbi.nlm.nih.gov/1378832/ DOI: 10.1016/s0021-9258(18)42066-2","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Arginine conversion and NO-dependent reporter guanylate cyclase activity","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"87b15ee6-14ce-55ae-88b3-85b1f0e3f17f","evidence_kind":"source_excerpt","locator":"Lines 476-487","start_line":476,"end_line":487,"excerpt":"### citrulline-calcium-nos\nThe calcium ionophore A23187 increased arginine-to-citrulline conversion in cells expressing human endothelial NOS.\nCondition category: normal\nnutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Calcium signaling can activate this enzyme; this experiment did not test taking calcium tablets.\norganism: Human NOS3 expressed in NIH3T3 cells; rat reporter fibroblasts\ntissue_or_cell_type: Arginine conversion and NO-dependent reporter guanylate cyclase activity\nexperimental_model: Functional expression and reporter-cell coculture\nlimitations: Heterologous expression; reporter activation supports bioactive NO production, not a clinical calcium supplementation effect.\nexposure: NOS3 transfection and calcium ionophore A23187\nevidence_span: {\"source_cache\": \"artifacts/citrulline-research/1378832.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"265be186f6d8172b272e7b1e75b4fbae12a6df78c7396cad499bce2b195b1206\", \"start_char\": 0, \"end_char\": 1652, \"text_sha256\": \"265be186f6d8172b272e7b1e75b4fbae12a6df78c7396cad499bce2b195b1206\"}\n[citrulline-p1378832] Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase. 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