{"id":"f10f124f-ff2f-58f8-aa2e-50620d0be222","stable_key":"b3c3f45a-50fb-5b79-98d7-5e5228df00db:cold-copper-free-dbh-activity","predicate":"reduces","statement":"Below a ratio of eight copper atoms per tetramer, the measured rate of enzymatic catalysis rose in proportion to the copper present rather than being maximal.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"9f3afdb3-2c71-5aae-bf20-c1b60addf7a1","mechanism_event_label":"Short the enzyme of copper and it runs proportionally slower.","subject":{"id":"76583ff9-f615-5cfe-bd31-f6201937ca87","slug":"copper-free-dbh","display_name":"Dopamine beta-hydroxylase below its eight-copper stoichiometry","entity_type_key":"protein_state"},"object":{"id":"485f2f39-c979-55f2-924e-7817830d1f53","slug":"dbh-catalysis","display_name":"Dopamine beta-hydroxylase catalytic turnover","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"9f3afdb3-2c71-5aae-bf20-c1b60addf7a1","stable_key":"b3c3f45a-50fb-5b79-98d7-5e5228df00db:cold-copper-free-dbh-activity-event","event_type":"biochemical_relationship","label":"Short the enzyme of copper and it runs proportionally slower.","description":"Below a ratio of eight copper atoms per tetramer, the measured rate of enzymatic catalysis rose in proportion to the copper present rather than being maximal.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9f0afdde-1ec1-5c8a-bb5e-f3b2b75f67f6","slug":"copper","display_name":"Copper","entity_type_key":"nutrient_element"},"role":"limiting_metal","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"76583ff9-f615-5cfe-bd31-f6201937ca87","slug":"copper-free-dbh","display_name":"Dopamine beta-hydroxylase below its eight-copper stoichiometry","entity_type_key":"protein_state"},"role":"subject","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":"target","stoichiometry":null,"state_label":"","sequence_order":2,"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/6323422.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"dac85ce0ad7c7d5994b97d55b129050a0e7ca8bf96943578d272054db6a07a62\", \"start_char\": 0, \"end_char\": 1346, \"text_sha256\": \"dac85ce0ad7c7d5994b97d55b129050a0e7ca8bf96943578d272054db6a07a62\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Copper titration of bovine adrenal dopamine beta-hydroxylase followed by NMR, EPR and inhibitor kinetics","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Titration with copper and measurement of catalytic rate","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Stoichiometry measured three independent ways. It establishes how much copper the enzyme needs, not how much copper a person needs.","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 enzyme","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Short the enzyme of copper and it runs proportionally slower.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[cold-p6323422] Kinetic and spectroscopic studies of the interaction of copper with dopamine beta-hydroxylase. (1984). https://pubmed.ncbi.nlm.nih.gov/6323422/ DOI: 10.1016/s0021-9258(17)43105-x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Adrenal medulla enzyme","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"63e32792-d58d-5448-b0f5-33a562616c2a","evidence_kind":"source_excerpt","locator":"Lines 572-583","start_line":572,"end_line":583,"excerpt":"### cold-copper-free-dbh-activity\nBelow a ratio of eight copper atoms per tetramer, the measured rate of enzymatic catalysis rose in proportion to the copper present rather than being maximal.\nCondition category: nutrient_deficiency\nnutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake.\nplain_language: Short the enzyme of copper and it runs proportionally slower.\norganism: Bovine enzyme\ntissue_or_cell_type: Adrenal medulla enzyme\nexperimental_model: Copper titration of bovine adrenal dopamine beta-hydroxylase followed by NMR, EPR and inhibitor kinetics\nlimitations: Stoichiometry measured three independent ways. It establishes how much copper the enzyme needs, not how much copper a person needs.\nexposure: Titration with copper and measurement of catalytic rate\nevidence_span: {\"source_cache\": \"artifacts/cold-research/6323422.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"dac85ce0ad7c7d5994b97d55b129050a0e7ca8bf96943578d272054db6a07a62\", \"start_char\": 0, \"end_char\": 1346, \"text_sha256\": \"dac85ce0ad7c7d5994b97d55b129050a0e7ca8bf96943578d272054db6a07a62\"}\n[cold-p6323422] Kinetic and spectroscopic studies of the interaction of copper with dopamine beta-hydroxylase. (1984). https://pubmed.ncbi.nlm.nih.gov/6323422/ DOI: 10.1016/s0021-9258(17)43105-x","model_system":"Copper titration of bovine adrenal dopamine beta-hydroxylase followed by NMR, EPR and inhibitor kinetics","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [cold-p6323422] Kinetic and spectroscopic studies of the interaction of copper with dopamine beta-hydroxylase. 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