{"id":"4cca9f54-599f-579b-9c04-339626f43622","stable_key":"b26c9d01-98fd-50d3-8f39-44db46961ee5:acetate-acetate-suppresses-pdh","predicate":"reduces","statement":"Acetate infusion increased muscle acetyl-CoA, citrate and acetylcarnitine, and resting active-form pyruvate dehydrogenase declined during 20 minutes of acetate infusion from 0.37 to 0.16 mmol per minute per kg wet weight, coinciding with an elevation in the acetyl-CoA to free CoA ratio from 0.28 to 0.73, whereas after the bicarbonate control infusion resting activity was similar to that before acetate.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"0f7e47ba-eb6c-53b4-9e39-95896392c39b","mechanism_event_label":"Raising blood acetate in people switched down the enzyme that commits glucose to being burned.","subject":{"id":"bc1dbe20-ce7f-5565-a3e2-b88bcdd68591","slug":"acetate-infusion","display_name":"Intravenous sodium acetate infusion","entity_type_key":"chemical_species"},"object":{"id":"cf592676-afa7-5724-bb20-d5864c65d0b7","slug":"pyruvate-dehydrogenase-activity","display_name":"Active-form pyruvate dehydrogenase in skeletal muscle","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"0f7e47ba-eb6c-53b4-9e39-95896392c39b","stable_key":"b26c9d01-98fd-50d3-8f39-44db46961ee5:acetate-acetate-suppresses-pdh-event","event_type":"observed_intervention","label":"Raising blood acetate in people switched down the enzyme that commits glucose to being burned.","description":"Acetate infusion increased muscle acetyl-CoA, citrate and acetylcarnitine, and resting active-form pyruvate dehydrogenase declined during 20 minutes of acetate infusion from 0.37 to 0.16 mmol per minute per kg wet weight, coinciding with an elevation in the acetyl-CoA to free CoA ratio from 0.28 to 0.73, whereas after the bicarbonate control infusion resting activity was similar to that before acetate.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e366e758-1fb0-5573-aed1-34f6df874ac7","slug":"acetate","display_name":"Acetate","entity_type_key":"small_molecule"},"role":"infused_metabolite","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8f23e8c5-c2e3-5f67-ab34-affa7f8c04ed","slug":"acetyl-coa-to-free-coa-ratio","display_name":"The ratio of acetyl-CoA to free coenzyme A in skeletal muscle","entity_type_key":"cellular_process"},"role":"mediating_ratio","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6d908873-0745-523a-96bf-9cf25bda2676","slug":"pyruvate-dehydrogenase-complex","display_name":"Human pyruvate dehydrogenase complex","entity_type_key":"protein_complex"},"role":"affected_complex","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"b7ed6e4c-e560-5cee-b68f-895f21862e6f","slug":"acetyl-coa","display_name":"Acetyl-CoA","entity_type_key":"small_molecule"},"role":"raised_metabolite","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"1c54abac-4dfd-5303-b0f4-37945245e18e","slug":"citrate","display_name":"Citrate","entity_type_key":"small_molecule"},"role":"raised_metabolite","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"5ce394a9-6ec6-56dd-866f-37d85c0556e4","slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"},"role":"raised_metabolite","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"bc1dbe20-ce7f-5565-a3e2-b88bcdd68591","slug":"acetate-infusion","display_name":"Intravenous sodium acetate infusion","entity_type_key":"chemical_species"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""},{"entity":{"id":"cf592676-afa7-5724-bb20-d5864c65d0b7","slug":"pyruvate-dehydrogenase-activity","display_name":"Active-form pyruvate dehydrogenase in skeletal muscle","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":7,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/acetate-research/7762627.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"343ba052925b754982d178cee1a1c2e3e0a3d1e940e6dd349989c7d6c2704f76\", \"start_char\": 0, \"end_char\": 1730, \"text_sha256\": \"343ba052925b754982d178cee1a1c2e3e0a3d1e940e6dd349989c7d6c2704f76\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Eight human subjects infused with sodium acetate at rest and during cycling, with muscle biopsies","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"400 mmol sodium acetate infused over 20 min rest, 5 min cycling at 40% and 15 min at 80% of maximal oxygen uptake, against a 400 mmol sodium bicarbonate control two weeks later","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A direct human measurement with a matched sodium control. The effect was present at rest and absent during exercise, so it is not a general property of raised acetate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion.","comparator":null,"unit":null,"notes":"","entity":{"slug":"acetic-acid","display_name":"Acetic acid","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Raising blood acetate in people switched down the enzyme that commits glucose to being burned.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[acetate-p7762627] Skeletal muscle pyruvate dehydrogenase activity during acetate infusion in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/7762627/ DOI: 10.1152/ajpendo.1995.268.5.e1007","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Skeletal muscle","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"f52bf135-f12f-5b46-8c6f-626ca06baa4f","evidence_kind":"source_excerpt","locator":"Lines 485-496","start_line":485,"end_line":496,"excerpt":"### acetate-acetate-suppresses-pdh\nAcetate infusion increased muscle acetyl-CoA, citrate and acetylcarnitine, and resting active-form pyruvate dehydrogenase declined during 20 minutes of acetate infusion from 0.37 to 0.16 mmol per minute per kg wet weight, coinciding with an elevation in the acetyl-CoA to free CoA ratio from 0.28 to 0.73, whereas after the bicarbonate control infusion resting activity was similar to that before acetate.\nCondition category: normal\nnutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion.\nplain_language: Raising blood acetate in people switched down the enzyme that commits glucose to being burned.\norganism: Human\ntissue_or_cell_type: Skeletal muscle\nexperimental_model: Eight human subjects infused with sodium acetate at rest and during cycling, with muscle biopsies\nlimitations: A direct human measurement with a matched sodium control. The effect was present at rest and absent during exercise, so it is not a general property of raised acetate.\nexposure: 400 mmol sodium acetate infused over 20 min rest, 5 min cycling at 40% and 15 min at 80% of maximal oxygen uptake, against a 400 mmol sodium bicarbonate control two weeks later\nevidence_span: {\"source_cache\": \"artifacts/acetate-research/7762627.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"343ba052925b754982d178cee1a1c2e3e0a3d1e940e6dd349989c7d6c2704f76\", \"start_char\": 0, \"end_char\": 1730, \"text_sha256\": \"343ba052925b754982d178cee1a1c2e3e0a3d1e940e6dd349989c7d6c2704f76\"}\n[acetate-p7762627] Skeletal muscle pyruvate dehydrogenase activity during acetate infusion in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/7762627/ DOI: 10.1152/ajpendo.1995.268.5.e1007","model_system":"Eight human subjects infused with sodium acetate at rest and during cycling, with muscle biopsies","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [acetate-p7762627] Skeletal muscle pyruvate dehydrogenase activity during acetate infusion in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/7762627/ DOI: 10.1152/ajpendo.1995.268.5.e1007","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"8356baaf-173c-5549-80cd-bbbb2007ffb5","stable_key":"import-b26c9d01-98fd-50d3-8f39-44db46961ee5","title":"Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21)","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":"1441d249b16db25c0d488407e5cc881222acffc2f16af88cb3197d9d5697bccc","revision_id":"9bfeb605-f589-5e99-84b9-e56968a3bc1f","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}