{"id":"1ada6a1e-162a-523d-8f5b-69294dea7873","stable_key":"research:dio3-thyroxine-inactivation","predicate":"deiodinates_to_produce","statement":"DIO3 catalyzes inner-ring deiodination of T4 to reverse T3 in functional placental-enzyme studies.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"literature_reviewed:direct_experimental","direction":"positive","is_public":true,"mechanism_event_id":"66ae7598-b3df-57a2-9840-e6effcef3c84","mechanism_event_label":"DIO3 lowers thyroid-hormone activity by converting T4 to reverse T3.","subject":{"id":"066966e9-8e21-5e5d-9082-12e81bc4b558","slug":"dio3","display_name":"DIO3","entity_type_key":"protein"},"object":{"id":"72f04ceb-85dc-5abb-88cc-4335ae4e0a0d","slug":"reverse-t3","display_name":"rT3","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"66ae7598-b3df-57a2-9840-e6effcef3c84","stable_key":"research:dio3-thyroxine-inactivation","event_type":"experimentally_scoped_interaction","label":"DIO3 lowers thyroid-hormone activity by converting T4 to reverse T3.","description":"DIO3 catalyzes inner-ring deiodination of T4 to reverse T3 in functional placental-enzyme studies.","status":"active","compartment":null,"participants":[{"entity":{"id":"066966e9-8e21-5e5d-9082-12e81bc4b558","slug":"dio3","display_name":"DIO3","entity_type_key":"protein"},"role":"catalyst","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"72f04ceb-85dc-5abb-88cc-4335ae4e0a0d","slug":"reverse-t3","display_name":"rT3","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"f2b25f38-ec94-57d0-a46d-dd0fee45f01e","slug":"thyroxine","display_name":"T4","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"experimental_model","value_text":"Human placental DIO3 cloning and functional expression.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This experiment-specific relationship does not establish a human dietary-deficiency threshold or supplementation benefit.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Human placental protein in an expression system","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"5114e766-a0a0-5f0e-b6b9-de019450463f","evidence_kind":"curated_literature_summary","locator":"lines 1020-1029","start_line":1020,"end_line":1029,"excerpt":"## dio3-thyroxine-inactivation\n\nDIO3 lowers thyroid-hormone activity by converting T4 to reverse T3.\n\nDIO3 catalyzes inner-ring deiodination of T4 to reverse T3 in functional placental-enzyme studies.\n\nExperimental model: Human placental DIO3 cloning and functional expression.\nOrganism: Human placental protein in an expression system\nLimitations: This experiment-specific relationship does not establish a human dietary-deficiency threshold or supplementation benefit.\nPrimary reference: [Type 3 iodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme](https://www.jci.org/articles/view/118299)","model_system":"Human placental DIO3 cloning and functional expression.","directness":"author_interpretation","verification_status":"secondary_verified","notes":"Curated summary; inspect the linked primary papers for original methods and results.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4f892f13-06ea-5199-a33c-a703f35c80ae","stable_key":"selenium-research-2026-09-17","title":"Selenium: literature corrections and mechanism additions","document_type":"curated_literature_review","citation_label":"Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually","file_path":"","sha256":"0b818b10c1c7120e5caf7f4d4019d7bd025d745692e424f515d3ef903c9ab7f3","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","review_status":"secondary_verified","notes":"Secondary curated summaries of primary experiments, with explicit models and limitations. Not archived primary full text."}}],"relations":[],"conflicts":[],"corrections":[],"research":{"topic":"Thyroid hormone processing","plain_language":"DIO3 lowers thyroid-hormone activity by converting T4 to reverse T3.","evidence_scope":"direct_experimental","papers":[{"key":"catalog-dio3-1995","title":"Type 3 iodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme","url":"https://www.jci.org/articles/view/118299","doi":"10.1172/JCI118299","year":1995,"model":"Human placental DIO3 cloning and functional expression.","summary":"Characterizes inner-ring deiodination of T4 and T3 into less active metabolites."}]}}