{"id":"1a318524-4f6d-5b0e-bd78-137de04aaecd","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-dhla-copper-oxygen","predicate":"can_release_copper_during","statement":"Oxidation destabilized DHLA-copper complexes near physiological pH, with renewed LDL oxidation and radical detection in the model.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"907b2661-d1c6-5035-9555-89a801b324c8","mechanism_event_label":"Metal binding was not a permanent guarantee against oxidation.","subject":{"id":"7a16802e-38d4-59ac-bafb-6dac1d45c31b","slug":"dhla-copper-complex","display_name":"Dihydrolipoic acid-copper complexes","entity_type_key":"chemical_species"},"object":{"id":"51d16a59-092e-5057-ab80-6a5c1939297f","slug":"copper-ldl-oxidation","display_name":"Copper-driven LDL oxidation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"907b2661-d1c6-5035-9555-89a801b324c8","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-dhla-copper-oxygen-event","event_type":"biochemical_relationship","label":"Metal binding was not a permanent guarantee against oxidation.","description":"Oxidation destabilized DHLA-copper complexes near physiological pH, with renewed LDL oxidation and radical detection in the model.","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":"released_metal","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"7a16802e-38d4-59ac-bafb-6dac1d45c31b","slug":"dhla-copper-complex","display_name":"Dihydrolipoic acid-copper complexes","entity_type_key":"chemical_species"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"51d16a59-092e-5057-ab80-6a5c1939297f","slug":"copper-ldl-oxidation","display_name":"Copper-driven LDL oxidation","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/ala-research/9680174.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1\", \"start_char\": 0, \"end_char\": 2034, \"text_sha256\": \"ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cell-free human LDL oxidation and electron-spin-resonance assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Copper 5 micromolar; DHLA 0–20 micromolar; oxygen and pH varied","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Metal binding, reduction and radical production depend on ratio, oxygen and pH; not evidence for human metal-detoxification efficacy.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"lipoic-acid","display_name":"Lipoic acid","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human LDL; cell-free chemistry","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Metal binding was not a permanent guarantee against oxidation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ala-p9680174] Thiol chelation of Cu2+ by dihydrolipoic acid prevents human low density lipoprotein peroxidation. (1998). https://pubmed.ncbi.nlm.nih.gov/9680174/ DOI: 10.1016/s0891-5849(98)00048-3","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"LDL and copper/DHLA solutions","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"15ef4e02-98aa-5cc5-8e74-aaeb315e26fb","evidence_kind":"source_excerpt","locator":"Lines 1066-1077","start_line":1066,"end_line":1077,"excerpt":"### ala-dhla-copper-oxygen\nOxidation destabilized DHLA-copper complexes near physiological pH, with renewed LDL oxidation and radical detection in the model.\nCondition category: normal\nnutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Metal binding was not a permanent guarantee against oxidation.\norganism: Human LDL; cell-free chemistry\ntissue_or_cell_type: LDL and copper/DHLA solutions\nexperimental_model: Cell-free human LDL oxidation and electron-spin-resonance assays\nlimitations: Metal binding, reduction and radical production depend on ratio, oxygen and pH; not evidence for human metal-detoxification efficacy.\nexposure: Copper 5 micromolar; DHLA 0–20 micromolar; oxygen and pH varied\nevidence_span: {\"source_cache\": \"artifacts/ala-research/9680174.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1\", \"start_char\": 0, \"end_char\": 2034, \"text_sha256\": \"ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1\"}\n[ala-p9680174] Thiol chelation of Cu2+ by dihydrolipoic acid prevents human low density lipoprotein peroxidation. 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