{"id":"f82e7d4e-c933-520c-8263-4deec3c83218","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:vc-enzyme-amidation-copper-recovery","predicate":"restores-after-chelation","statement":"Pituitary peptide-amidating activity inhibited by divalent-metal chelators was restored above control by copper addition; the assayed reaction also required molecular oxygen.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"408f67e3-73f3-5d9b-9959-78aca34b324b","mechanism_event_label":"Vitamin C and copper participate together, and removing available metal stops this peptide-processing assay.","subject":{"id":"2a870bb5-05a0-5e51-a70c-a9a843a8b571","slug":"copper-ii","display_name":"Copper(II) ion","entity_type_key":"ion"},"object":{"id":"a34aa332-22a3-505c-899f-0e8a2b7bc2b3","slug":"bovine-pam","display_name":"Bovine peptidylglycine alpha-amidating monooxygenase","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"408f67e3-73f3-5d9b-9959-78aca34b324b","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:vc-enzyme-amidation-copper-recovery-event","event_type":"biochemical_relationship","label":"Vitamin C and copper participate together, and removing available metal stops this peptide-processing assay.","description":"Pituitary peptide-amidating activity inhibited by divalent-metal chelators was restored above control by copper addition; the assayed reaction also required molecular oxygen.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"2a870bb5-05a0-5e51-a70c-a9a843a8b571","slug":"copper-ii","display_name":"Copper(II) ion","entity_type_key":"ion"},"role":"restoring-metal","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"role":"reducing-cofactor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a34aa332-22a3-505c-899f-0e8a2b7bc2b3","slug":"bovine-pam","display_name":"Bovine peptidylglycine alpha-amidating monooxygenase","entity_type_key":"protein"},"role":"bovine-enzyme-source","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"0df518fc-508b-5187-94c1-22642c4cb772","slug":"d-tyr-val-gly","display_name":"D-Tyr-Val-Gly","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"899c7ab0-6f81-5b38-a6bd-fbb33d66ac8d","slug":"oxygen","display_name":"Molecular oxygen","entity_type_key":"small_molecule"},"role":"cosubstrate","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Rat pituitary and bovine intermediate-pituitary secretory-granule preparations","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Synthetic D-Tyr-Val-Gly amidation with varied ascorbate, oxygen and divalent-metal chelators/copper.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Study included rat and bovine preparations; this cofactor observation is scoped to those preparations rather than a human nutritional copper trial.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin C research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-c","display_name":"Vitamin C","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Rattus norvegicus; Bos taurus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Vitamin C and copper participate together, and removing available metal stops this peptide-processing assay.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[pam1983] Identification in pituitary tissue of a peptide alpha-amidation activity that acts on glycine-extended peptides and requires molecular oxygen, copper, and ascorbic acid. (1983). https://pubmed.ncbi.nlm.nih.gov/6576381/ DOI: 10.1073/pnas.80.16.5144","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Pituitary secretory granules","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"bf80421e-d1db-5d13-a261-4b141ffbb680","evidence_kind":"source_excerpt","locator":"Lines 872-883","start_line":872,"end_line":883,"excerpt":"### vc-enzyme-amidation-copper-recovery\nPituitary peptide-amidating activity inhibited by divalent-metal chelators was restored above control by copper addition; the assayed reaction also required molecular oxygen.\nCondition category: normal\nnutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Vitamin C and copper participate together, and removing available metal stops this peptide-processing assay.\norganism: Rattus norvegicus; Bos taurus\ntissue_or_cell_type: Pituitary secretory granules\nexperimental_model: Rat pituitary and bovine intermediate-pituitary secretory-granule preparations\nlimitations: Study included rat and bovine preparations; this cofactor observation is scoped to those preparations rather than a human nutritional copper trial.\ncross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.\nexposure: Synthetic D-Tyr-Val-Gly amidation with varied ascorbate, oxygen and divalent-metal chelators/copper.\n[pam1983] Identification in pituitary tissue of a peptide alpha-amidation activity that acts on glycine-extended peptides and requires molecular oxygen, copper, and ascorbic acid. (1983). https://pubmed.ncbi.nlm.nih.gov/6576381/ DOI: 10.1073/pnas.80.16.5144","model_system":"Rat pituitary and bovine intermediate-pituitary secretory-granule preparations","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [pam1983] Identification in pituitary tissue of a peptide alpha-amidation activity that acts on glycine-extended peptides and requires molecular oxygen, copper, and ascorbic acid. 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