{"id":"d6849992-ea30-58fc-940d-f701131e9e7b","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:iodine-syn-lysosomal-inhibition","predicate":"reduces","statement":"Combined inhibition of cathepsins B, D and L reduced long-incubation iodoamino-acid release from radioiodinated rabbit TG by 80–90%.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"faa14781-8ffe-56fb-94a6-25f2c643e9b4","mechanism_event_label":"Blocking these proteases greatly reduced release of iodinated amino acids from TG.","subject":{"id":"3035e1c6-a254-5570-93e3-d0bd398ed113","slug":"lysosomal-cathepsin-inhibitor-combination","display_name":"Experimental cathepsin B/D/L inhibitor combination","entity_type_key":"chemical_species"},"object":{"id":"29fb1815-a373-5d03-86fd-bc23b114324b","slug":"lysosomal-iodoamino-acid-release","display_name":"Lysosomal iodoamino acid release","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"faa14781-8ffe-56fb-94a6-25f2c643e9b4","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:iodine-syn-lysosomal-inhibition-event","event_type":"biochemical_relationship","label":"Blocking these proteases greatly reduced release of iodinated amino acids from TG.","description":"Combined inhibition of cathepsins B, D and L reduced long-incubation iodoamino-acid release from radioiodinated rabbit TG by 80–90%.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9dac418b-7471-5cc6-92b1-d47e58dc5301","slug":"rabbit-thyroglobulin","display_name":"Rabbit thyroglobulin","entity_type_key":"protein"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0b1b8e44-4be8-5734-9795-9f70abbbe1d0","slug":"human-cathepsin-b","display_name":"Human cathepsin B","entity_type_key":"protein"},"role":"inhibited_enzyme","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e7843eb3-8df2-5843-91c2-22f0b2150a06","slug":"human-cathepsin-l","display_name":"Human cathepsin L","entity_type_key":"protein"},"role":"inhibited_enzyme","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5339ea98-c4bd-5977-a59c-215c6332a5a4","slug":"human-cathepsin-d","display_name":"Human cathepsin D","entity_type_key":"protein"},"role":"inhibited_enzyme","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"3035e1c6-a254-5570-93e3-d0bd398ed113","slug":"lysosomal-cathepsin-inhibitor-combination","display_name":"Experimental cathepsin B/D/L inhibitor combination","entity_type_key":"chemical_species"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"29fb1815-a373-5d03-86fd-bc23b114324b","slug":"lysosomal-iodoamino-acid-release","display_name":"Lysosomal iodoamino acid release","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/iodine-synthesis-sources/1903699.json\", \"json_field\": \"abstractText\", \"text_sha256\": \"2fecda8478b67ba815425948ac7198157a2d0e8fe18381b9bf3a9fd0e5190410\", \"text_characters\": 2209, \"note\": \"Exact publisher passage retained in the cited local source cache; locator and digest supplied here.\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"In-vivo-radioiodinated rabbit TG incubated with human thyroid lysosomal extracts and protease inhibitors","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Rabbit [125I]TG with human thyroid lysosomal extracts: 20–45 minutes for peptides; 8 and 24 hours for iodoamino-acid release. Combined protease inhibition.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Iodoamino-acid endpoint includes iodothyronines and iodotyrosines; do not assign the percentage specifically to T4.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Iodine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"iodine","display_name":"Iodine","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Oryctolagus cuniculus substrate; Homo sapiens enzymes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Blocking these proteases greatly reduced release of iodinated amino acids from TG.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[iodine-syn-lysosome1991] Proteolytic processing of thyroglobulin by extracts of thyroid lysosomes. (1991). https://pubmed.ncbi.nlm.nih.gov/1903699/ DOI: 10.1210/endo-128-6-3073","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Human thyroid lysosomal extracts","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"8fd09173-59ed-53da-a88d-da48157ffe40","evidence_kind":"source_excerpt","locator":"Lines 674-686","start_line":674,"end_line":686,"excerpt":"### iodine-syn-lysosomal-inhibition\nCombined inhibition of cathepsins B, D and L reduced long-incubation iodoamino-acid release from radioiodinated rabbit TG by 80–90%.\nCondition category: normal\nnutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Blocking these proteases greatly reduced release of iodinated amino acids from TG.\norganism: Oryctolagus cuniculus substrate; Homo sapiens enzymes\ntissue_or_cell_type: Human thyroid lysosomal extracts\nexperimental_model: In-vivo-radioiodinated rabbit TG incubated with human thyroid lysosomal extracts and protease inhibitors\nlimitations: Iodoamino-acid endpoint includes iodothyronines and iodotyrosines; do not assign the percentage specifically to T4.\nexposure: Rabbit [125I]TG with human thyroid lysosomal extracts: 20–45 minutes for peptides; 8 and 24 hours for iodoamino-acid release. Combined protease inhibition.\ncross_nutrient: false\nevidence_span: {\"source_cache\": \"artifacts/iodine-synthesis-sources/1903699.json\", \"json_field\": \"abstractText\", \"text_sha256\": \"2fecda8478b67ba815425948ac7198157a2d0e8fe18381b9bf3a9fd0e5190410\", \"text_characters\": 2209, \"note\": \"Exact publisher passage retained in the cited local source cache; locator and digest supplied here.\"}\n[iodine-syn-lysosome1991] Proteolytic processing of thyroglobulin by extracts of thyroid lysosomes. (1991). https://pubmed.ncbi.nlm.nih.gov/1903699/ DOI: 10.1210/endo-128-6-3073","model_system":"In-vivo-radioiodinated rabbit TG incubated with human thyroid lysosomal extracts and protease inhibitors","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [iodine-syn-lysosome1991] Proteolytic processing of thyroglobulin by extracts of thyroid lysosomes. 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