{"id":"43642cc8-8972-5bfd-a29e-2274199541da","stable_key":"e3f6ce02-0bd7-5103-acc1-68503ab6751b:tmlhe-histone-loss","predicate":"decreases_in_recorded_comparison","statement":"TMLHE knockdown reduced histone acetylation and nuclear acetyl-CoA in the 2026 cancer-cell study.","claim_class":"observational","status":"source_recorded","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"d1a7356b-cd81-5b3c-a456-bfef999aa0a3","mechanism_event_label":"TMLHE knockdown reduced histone acetylation and nuclear acetyl-CoA in the 2026 cancer-cell study.","subject":{"id":"3f888cec-e779-5b46-bd59-e5317d4bf6aa","slug":"tmlhe","display_name":"Trimethyllysine hydroxylase / TMLHE","entity_type_key":"protein"},"object":{"id":"9b97798e-bd7b-54c6-b5e8-0e8800223543","slug":"human-cancer-histone-acetylation","display_name":"Human cancer-cell histone acetylation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"d1a7356b-cd81-5b3c-a456-bfef999aa0a3","stable_key":"e3f6ce02-0bd7-5103-acc1-68503ab6751b:tmlhe-histone-loss-event","event_type":"experimental_observation","label":"TMLHE knockdown reduced histone acetylation and nuclear acetyl-CoA in the 2026 cancer-cell study.","description":"### tmlhe-histone-loss\n\nTMLHE knockdown reduced histone acetylation and nuclear acetyl-CoA in the 2026 cancer-cell study.\nL-carnitine or ALCAR rescued acetylation downstream of TMLHE loss; alpha-ketoglutarate did not. This distinguishes a blocked enzyme step from insufficient upstream cosubstrate.\nModel and exposure: Human FT282-CCNE1 and Ovcar8-CCNE1 models; Fig. 3g,j.\nLimitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.\nReference: αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | 2026 | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3f888cec-e779-5b46-bd59-e5317d4bf6aa","slug":"tmlhe","display_name":"Trimethyllysine hydroxylase / TMLHE","entity_type_key":"protein"},"role":"tested factor","stoichiometry":null,"state_label":"TMLHE knockdown","sequence_order":0,"notes":""},{"entity":{"id":"9b97798e-bd7b-54c6-b5e8-0e8800223543","slug":"human-cancer-histone-acetylation","display_name":"Human cancer-cell histone acetylation","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"decrease","sequence_order":1,"notes":""},{"entity":{"id":"628ddc2d-e4d9-59c7-ae76-0c0cab80a6b1","slug":"2-oxoglutarate","display_name":"2-Oxoglutarate","entity_type_key":"small_molecule"},"role":"upstream cosubstrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"6e34c035-9371-578f-b799-fd2a14e9e40f","slug":"l-carnitine","display_name":"L-Carnitine","entity_type_key":"small_molecule"},"role":"downstream rescue","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"5ce394a9-6ec6-56dd-866f-37d85c0556e4","slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"},"role":"downstream rescue","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"b7ed6e4c-e560-5cee-b68f-895f21862e6f","slug":"acetyl-coa","display_name":"Acetyl-CoA","entity_type_key":"small_molecule"},"role":"measured compartmental metabolite","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_contrast","value_text":"{\"intervention\": \"TMLHE knockdown\", \"comparator\": \"Control shRNA\", \"endpoint\": \"TMLHE knockdown reduced histone acetylation and nuclear acetyl-CoA in the 2026 cancer-cell study.\", \"effect_direction\": \"decrease\", \"combination\": \"single\", \"conditions\": []}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"Human FT282-CCNE1 and Ovcar8-CCNE1 models; Fig. 3g,j.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Source-derived curation with stated access limits; ungraded, not independent replication.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation.","comparator":null,"unit":null,"notes":"","entity":{"slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"TMLHE knockdown reduced histone acetylation and nuclear acetyl-CoA in the 2026 cancer-cell study.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference tmlhe-histone-loss; L-carnitine or ALCAR rescued acetylation downstream of TMLHE loss; alpha-ketoglutarate did not. This distinguishes a blocked enzyme step from insufficient upstream cosubstrate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"3554908a-822a-5834-ae6b-5bfd139250f1","evidence_kind":"source_excerpt","locator":"Lines 288-294","start_line":288,"end_line":294,"excerpt":"### tmlhe-histone-loss\n\nTMLHE knockdown reduced histone acetylation and nuclear acetyl-CoA in the 2026 cancer-cell study.\nL-carnitine or ALCAR rescued acetylation downstream of TMLHE loss; alpha-ketoglutarate did not. This distinguishes a blocked enzyme step from insufficient upstream cosubstrate.\nModel and exposure: Human FT282-CCNE1 and Ovcar8-CCNE1 models; Fig. 3g,j.\nLimitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.\nReference: αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | 2026 | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","model_system":"Human FT282-CCNE1 and Ovcar8-CCNE1 models; Fig. 3g,j.","directness":"reported_statement","verification_status":"source_recorded","notes":"Original paraphrase in the retained reviewed reference, not a verbatim primary-paper quotation. Access level is explicit.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"2588f904-245a-597a-8a12-65118013fb90","stable_key":"import-e3f6ce02-0bd7-5103-acc1-68503ab6751b","title":"Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026)","document_type":"imported_text","citation_label":"AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed.","file_path":"","sha256":"84cc82d6fbb0fd5d73c4ce779e9f88e7f0184ba2d29b18ad0f153815380f2975","revision_id":"dac7a950-dbe5-5c7a-9c70-2ea711d5c71a","review_status":"source_recorded","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}