{"id":"60274b54-842a-5679-bcba-22c9d6158934","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-sig-gamma-te-hmgcr-turnover","predicate":"accelerates","statement":"At 10 µM gamma-tocotrienol, HepG2 HMG-CoA reductase degradation increased 2.4-fold and its half-life fell from 3.73 to 1.59 h, measured by [35S]methionine pulse-chase and immunoprecipitation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"c43dedbf-22c1-55d0-9d59-22c757729398","mechanism_event_label":"Gamma-tocotrienol made the cholesterol-synthesis enzyme turn over faster in cultured human liver tumor cells.","subject":{"id":"27fc7c66-efe2-57b6-988b-560bb242182d","slug":"gamma-tocotrienol","display_name":"Gamma-tocotrienol","entity_type_key":"small_molecule"},"object":{"id":"a5fb755e-0e91-56aa-abd6-d52f10a2033b","slug":"hmgcr-protein-degradation","display_name":"HMG-CoA reductase protein degradation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"c43dedbf-22c1-55d0-9d59-22c757729398","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-sig-gamma-te-hmgcr-turnover-event","event_type":"biochemical_relationship","label":"Gamma-tocotrienol made the cholesterol-synthesis enzyme turn over faster in cultured human liver tumor cells.","description":"At 10 µM gamma-tocotrienol, HepG2 HMG-CoA reductase degradation increased 2.4-fold and its half-life fell from 3.73 to 1.59 h, measured by [35S]methionine pulse-chase and immunoprecipitation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a8b5e5e1-b5b5-551d-8fd4-72f7b45de78a","slug":"hmgcr","display_name":"HMG-CoA reductase (HMGCR)","entity_type_key":"protein"},"role":"protein undergoing degradation","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"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":1,"notes":""},{"entity":{"id":"a5fb755e-0e91-56aa-abd6-d52f10a2033b","slug":"hmgcr-protein-degradation","display_name":"HMG-CoA reductase protein degradation","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Radiolabeled protein pulse-chase and HMGCR immunoprecipitation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"10 µM gamma-tocotrienol; reported HMGCR half-life 3.73 h control versus 1.59 h treated.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Primary abstract only; these data do not by themselves identify Insig proteins or prove direct binding to the reductase. Human supplementation effects cannot be inferred.","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 made the cholesterol-synthesis enzyme turn over faster in cultured human liver tumor 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":"f56e4981-1d52-5056-8033-0f5a2c6d1d1c","evidence_kind":"source_excerpt","locator":"Lines 1115-1126","start_line":1115,"end_line":1126,"excerpt":"### e-sig-gamma-te-hmgcr-turnover\nAt 10 µM gamma-tocotrienol, HepG2 HMG-CoA reductase degradation increased 2.4-fold and its half-life fell from 3.73 to 1.59 h, measured by [35S]methionine pulse-chase and immunoprecipitation.\nCondition category: normal\nnutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Gamma-tocotrienol made the cholesterol-synthesis enzyme turn over faster in cultured human liver tumor cells.\norganism: Homo sapiens\ntissue_or_cell_type: Hepatoma cell culture\nexperimental_model: Radiolabeled protein pulse-chase and HMGCR immunoprecipitation\nlimitations: Primary abstract only; these data do not by themselves identify Insig proteins or prove direct binding to the reductase. Human supplementation effects cannot be inferred.\nexposure: 10 µM gamma-tocotrienol; reported HMGCR half-life 3.73 h control versus 1.59 h treated.\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 protein pulse-chase and HMGCR immunoprecipitation","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}