{"id":"c84ed896-d484-5653-bc64-ed178fd10946","stable_key":"b3c3f45a-50fb-5b79-98d7-5e5228df00db:cold-ascorbate-depletion-in-granule","predicate":"reduces","statement":"Incubation with tyramine produced a time-dependent decrease in reduced intragranular ascorbate proportional to extragranular tyramine concentration over 50 microM to 2 mM.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"bb3c6434-1cdc-526e-8235-218c4c4b37be","mechanism_event_label":"Every molecule of noradrenaline made costs the vesicle a molecule of vitamin C.","subject":{"id":"485f2f39-c979-55f2-924e-7817830d1f53","slug":"dbh-catalysis","display_name":"Dopamine beta-hydroxylase catalytic turnover","entity_type_key":"cellular_process"},"object":{"id":"fcffefc5-21c3-53bd-a3f7-adb8e58180bd","slug":"intragranular-ascorbate","display_name":"Reduced ascorbate inside the chromaffin granule","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"bb3c6434-1cdc-526e-8235-218c4c4b37be","stable_key":"b3c3f45a-50fb-5b79-98d7-5e5228df00db:cold-ascorbate-depletion-in-granule-event","event_type":"biochemical_relationship","label":"Every molecule of noradrenaline made costs the vesicle a molecule of vitamin C.","description":"Incubation with tyramine produced a time-dependent decrease in reduced intragranular ascorbate proportional to extragranular tyramine concentration over 50 microM to 2 mM.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"role":"consumed_cofactor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"da1a7137-08f2-5a36-8bb6-377fbd32e327","slug":"vitamin-c","display_name":"Vitamin C","entity_type_key":"chemical_species"},"role":"nutrient_source","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"485f2f39-c979-55f2-924e-7817830d1f53","slug":"dbh-catalysis","display_name":"Dopamine beta-hydroxylase catalytic turnover","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"fcffefc5-21c3-53bd-a3f7-adb8e58180bd","slug":"intragranular-ascorbate","display_name":"Reduced ascorbate inside the chromaffin granule","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/cold-research/3949732.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9db1233389aeb375adfd655ea04f39ccb05e22773f367aaa1292bb21698242e1\", \"start_char\": 0, \"end_char\": 2000, \"text_sha256\": \"9db1233389aeb375adfd655ea04f39ccb05e22773f367aaa1292bb21698242e1\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Intact bovine chromaffin granules undergoing dopamine beta-hydroxylase turnover with labelled ascorbate","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Tyramine- or dopamine-stimulated turnover with extragranular ascorbate","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"An in vitro demonstration in intact granules. Ascorbate itself does not cross the membrane, which is precisely why a shuttle is required.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake.","comparator":null,"unit":null,"notes":"","entity":{"slug":"cold-water-immersion","display_name":"Cold water immersion","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Bovine","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Every molecule of noradrenaline made costs the vesicle a molecule of vitamin C.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[cold-p3949732] Evidence for an ascorbate shuttle for the transfer of reducing equivalents across chromaffin granule membranes. 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Ascorbate itself does not cross the membrane, which is precisely why a shuttle is required.\nexposure: Tyramine- or dopamine-stimulated turnover with extragranular ascorbate\nevidence_span: {\"source_cache\": \"artifacts/cold-research/3949732.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"9db1233389aeb375adfd655ea04f39ccb05e22773f367aaa1292bb21698242e1\", \"start_char\": 0, \"end_char\": 2000, \"text_sha256\": \"9db1233389aeb375adfd655ea04f39ccb05e22773f367aaa1292bb21698242e1\"}\n[cold-p3949732] Evidence for an ascorbate shuttle for the transfer of reducing equivalents across chromaffin granule membranes. (1986). https://pubmed.ncbi.nlm.nih.gov/3949732/ DOI: 10.1016/s0021-9258(17)35819-2","model_system":"Intact bovine chromaffin granules undergoing dopamine beta-hydroxylase turnover with labelled ascorbate","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [cold-p3949732] Evidence for an ascorbate shuttle for the transfer of reducing equivalents across chromaffin granule membranes. 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