{"id":"15f32c00-10e2-509c-8d8c-ec0278466eec","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:iodine-syn-heme-trafficking","predicate":"reduces_surface_delivery","statement":"In CHO cells expressing human TPO, inhibition of heme biosynthesis by succinylacetone decreased surface TPO expression by approximately 80%.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"a54fc1ee-21ed-5d00-aa4a-ede106fb8f11","mechanism_event_label":"Blocking heme production kept much of TPO from reaching the surface.","subject":{"id":"8b701577-fe59-56c6-9dcf-eb2488694b92","slug":"succinylacetone","display_name":"Succinylacetone","entity_type_key":"small_molecule"},"object":{"id":"d5e001d7-78aa-5636-8891-07672ef87e0f","slug":"tpo","display_name":"Human thyroid peroxidase","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"a54fc1ee-21ed-5d00-aa4a-ede106fb8f11","stable_key":"aaa7baba-8689-56ab-ba1e-b71542bcb8e9:iodine-syn-heme-trafficking-event","event_type":"biochemical_relationship","label":"Blocking heme production kept much of TPO from reaching the surface.","description":"In CHO cells expressing human TPO, inhibition of heme biosynthesis by succinylacetone decreased surface TPO expression by approximately 80%.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"2e1f7e0a-8b54-5ea3-9d34-01e7167f9097","slug":"heme","display_name":"Heme","entity_type_key":"small_molecule"},"role":"required_prosthetic_group","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"89bcaf42-b4ab-5760-8c2e-44eace10cee0","slug":"iron","display_name":"Iron","entity_type_key":"nutrient_element"},"role":"heme_metal","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8b701577-fe59-56c6-9dcf-eb2488694b92","slug":"succinylacetone","display_name":"Succinylacetone","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"d5e001d7-78aa-5636-8891-07672ef87e0f","slug":"tpo","display_name":"Human thyroid peroxidase","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/iodine-synthesis-sources/10187846.json\", \"json_field\": \"abstractText\", \"text_sha256\": \"97f8a86c7effd5754e2b61c65d769de9e86678a7398c5eb20a0e88ac49a8fdbb\", \"text_characters\": 1855, \"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":"CHO cells expressing human TPO; additional primary thyroid cultures","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Succinylacetone; concentration not stated in abstract.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Pharmacological heme synthesis perturbation; not evidence of a dietary iron threshold.","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":"Homo sapiens protein; Cricetulus griseus host cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Blocking heme production kept much of TPO from reaching the surface.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[iodine-syn-tpo1999] Role of heme in intracellular trafficking of thyroperoxidase and involvement of H2O2 generated at the apical surface of thyroid cells in autocatalytic covalent heme binding. (1999). https://pubmed.ncbi.nlm.nih.gov/10187846/ DOI: 10.1074/jbc.274.15.10533","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"CHO endoplasmic reticulum and cell surface","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"6c72710c-d569-5f16-935d-3d5856322388","evidence_kind":"source_excerpt","locator":"Lines 576-588","start_line":576,"end_line":588,"excerpt":"### iodine-syn-heme-trafficking\nIn CHO cells expressing human TPO, inhibition of heme biosynthesis by succinylacetone decreased surface TPO expression by approximately 80%.\nCondition category: normal\nnutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Blocking heme production kept much of TPO from reaching the surface.\norganism: Homo sapiens protein; Cricetulus griseus host cells\ntissue_or_cell_type: CHO endoplasmic reticulum and cell surface\nexperimental_model: CHO cells expressing human TPO; additional primary thyroid cultures\nlimitations: Pharmacological heme synthesis perturbation; not evidence of a dietary iron threshold.\nexposure: Succinylacetone; concentration not stated in abstract.\ncross_nutrient: true\nevidence_span: {\"source_cache\": \"artifacts/iodine-synthesis-sources/10187846.json\", \"json_field\": \"abstractText\", \"text_sha256\": \"97f8a86c7effd5754e2b61c65d769de9e86678a7398c5eb20a0e88ac49a8fdbb\", \"text_characters\": 1855, \"note\": \"Exact publisher passage retained in the cited local source cache; locator and digest supplied here.\"}\n[iodine-syn-tpo1999] Role of heme in intracellular trafficking of thyroperoxidase and involvement of H2O2 generated at the apical surface of thyroid cells in autocatalytic covalent heme binding. (1999). https://pubmed.ncbi.nlm.nih.gov/10187846/ DOI: 10.1074/jbc.274.15.10533","model_system":"CHO cells expressing human TPO; additional primary thyroid cultures","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [iodine-syn-tpo1999] Role of heme in intracellular trafficking of thyroperoxidase and involvement of H2O2 generated at the apical surface of thyroid cells in autocatalytic covalent heme binding. (1999). https://pubmed.ncbi.nlm.nih.gov/10187846/ DOI: 10.1074/jbc.274.15.10533","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"76da623d-a34a-5a5c-a942-d7571a85c486","stable_key":"import-aaa7baba-8689-56ab-ba1e-b71542bcb8e9","title":"Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"a4885eb6f58bad4a4514c958b63834619e57b10aa7f694aa97d0f65c7d36548f","revision_id":"ea8001a1-b576-5eda-a193-883c7ad59b73","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}