{"id":"629cd451-1d77-5547-a8ac-1cfc939dc65b","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-sig-gamma-te-cholesterol","predicate":"inhibits","statement":"In HepG2 cells, gamma-tocotrienol inhibited incorporation of [14C]acetate into cholesterol with approximately 50% inhibition at 2 µM and maximal approximately 80% inhibition within 6 h, while incorporation of [3H]mevalonate was not inhibited.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"eb9a4059-8f38-5c8d-8a48-899847b31ba1","mechanism_event_label":"Gamma-tocotrienol reduced cholesterol production from an early precursor, while leaving production from the later precursor mevalonate intact in cultured liver cells.","subject":{"id":"27fc7c66-efe2-57b6-988b-560bb242182d","slug":"gamma-tocotrienol","display_name":"Gamma-tocotrienol","entity_type_key":"small_molecule"},"object":{"id":"ef9c7fea-7698-5a51-a415-318ec65de8b5","slug":"cholesterol-biosynthesis","display_name":"Cholesterol biosynthesis","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"eb9a4059-8f38-5c8d-8a48-899847b31ba1","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-sig-gamma-te-cholesterol-event","event_type":"biochemical_relationship","label":"Gamma-tocotrienol reduced cholesterol production from an early precursor, while leaving production from the later precursor mevalonate intact in cultured liver cells.","description":"In HepG2 cells, gamma-tocotrienol inhibited incorporation of [14C]acetate into cholesterol with approximately 50% inhibition at 2 µM and maximal approximately 80% inhibition within 6 h, while incorporation of [3H]mevalonate was not inhibited.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"27fc7c66-efe2-57b6-988b-560bb242182d","slug":"gamma-tocotrienol","display_name":"Gamma-tocotrienol","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ef9c7fea-7698-5a51-a415-318ec65de8b5","slug":"cholesterol-biosynthesis","display_name":"Cholesterol biosynthesis","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Radiolabeled precursor incorporation in HepG2 cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Gamma-tocotrienol approximately 2 µM for half-maximal inhibition; response developed within 6 h.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Primary abstract only; media and viability protocol unavailable. Tracer localization supports action upstream of mevalonate use, not a human cholesterol-lowering recommendation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin E research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-e","display_name":"Vitamin E","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Gamma-tocotrienol reduced cholesterol production from an early precursor, while leaving production from the later precursor mevalonate intact in cultured liver cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[parker1993] Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. (1993). https://pubmed.ncbi.nlm.nih.gov/8388388/ DOI: 10.1016/s0021-9258(18)82115-9","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Hepatoma cell culture","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b4dec546-e472-56ea-b543-92baacdce228","evidence_kind":"source_excerpt","locator":"Lines 1102-1113","start_line":1102,"end_line":1113,"excerpt":"### e-sig-gamma-te-cholesterol\nIn HepG2 cells, gamma-tocotrienol inhibited incorporation of [14C]acetate into cholesterol with approximately 50% inhibition at 2 µM and maximal approximately 80% inhibition within 6 h, while incorporation of [3H]mevalonate was not inhibited.\nCondition category: normal\nnutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Gamma-tocotrienol reduced cholesterol production from an early precursor, while leaving production from the later precursor mevalonate intact in cultured liver cells.\norganism: Homo sapiens\ntissue_or_cell_type: Hepatoma cell culture\nexperimental_model: Radiolabeled precursor incorporation in HepG2 cells\nlimitations: Primary abstract only; media and viability protocol unavailable. Tracer localization supports action upstream of mevalonate use, not a human cholesterol-lowering recommendation.\nexposure: Gamma-tocotrienol approximately 2 µM for half-maximal inhibition; response developed within 6 h.\ncross_nutrient: false\n[parker1993] Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. (1993). https://pubmed.ncbi.nlm.nih.gov/8388388/ DOI: 10.1016/s0021-9258(18)82115-9","model_system":"Radiolabeled precursor incorporation in HepG2 cells","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [parker1993] Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. (1993). https://pubmed.ncbi.nlm.nih.gov/8388388/ DOI: 10.1016/s0021-9258(18)82115-9","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"3ac41dba-4727-5116-a556-ac3bbb0dc41c","stable_key":"import-e0ea2d6a-7429-5e9f-b774-41e5e3288da3","title":"Vitamin E: transport, membrane protection 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":"a90b6565e092c6a2da07f74cf758792c2cf63b40746260c8ff12bd64322c36f4","revision_id":"956793d1-23e4-5397-9291-25c1732a8e02","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}