{"id":"4187e25f-e71c-5184-80dc-92d20a1a0f51","stable_key":"b26c9d01-98fd-50d3-8f39-44db46961ee5:acetate-exercise-overrides","predicate":"preserves_measured_pool","statement":"During exercise acetyl-CoA, citrate and the acetyl-CoA to free CoA ratio were further elevated and the differences present at rest were resolved, with active-form pyruvate dehydrogenase increasing to the same extent with acetate and with the control infusion, so that during exercise its regulation appeared independent of variations in the acetyl-CoA to free CoA ratio and acetate infusion was not effective in perturbing the glucose-fatty acid cycle.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"95c55f2b-a071-5c6f-a53b-1cbcc51452b3","mechanism_event_label":"During exercise the muscle ignored the extra acetate entirely.","subject":{"id":"64627254-5e16-5a14-a97c-97875b74ddf5","slug":"cycling-exercise","display_name":"Cycling exercise at 40 and 80 percent of maximal oxygen uptake","entity_type_key":"cellular_process"},"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":"95c55f2b-a071-5c6f-a53b-1cbcc51452b3","stable_key":"b26c9d01-98fd-50d3-8f39-44db46961ee5:acetate-exercise-overrides-event","event_type":"observed_intervention","label":"During exercise the muscle ignored the extra acetate entirely.","description":"During exercise acetyl-CoA, citrate and the acetyl-CoA to free CoA ratio were further elevated and the differences present at rest were resolved, with active-form pyruvate dehydrogenase increasing to the same extent with acetate and with the control infusion, so that during exercise its regulation appeared independent of variations in the acetyl-CoA to free CoA ratio and acetate infusion was not effective in perturbing the glucose-fatty acid cycle.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"bc1dbe20-ce7f-5565-a3e2-b88bcdd68591","slug":"acetate-infusion","display_name":"Intravenous sodium acetate infusion","entity_type_key":"chemical_species"},"role":"tested_exposure","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":"uncoupled_ratio","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"64627254-5e16-5a14-a97c-97875b74ddf5","slug":"cycling-exercise","display_name":"Cycling exercise at 40 and 80 percent of maximal oxygen uptake","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"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":3,"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":"During exercise the muscle ignored the extra acetate entirely.","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":"ad1a6517-9a2d-5b96-86ce-fa341669882a","evidence_kind":"source_excerpt","locator":"Lines 498-509","start_line":498,"end_line":509,"excerpt":"### acetate-exercise-overrides\nDuring exercise acetyl-CoA, citrate and the acetyl-CoA to free CoA ratio were further elevated and the differences present at rest were resolved, with active-form pyruvate dehydrogenase increasing to the same extent with acetate and with the control infusion, so that during exercise its regulation appeared independent of variations in the acetyl-CoA to free CoA ratio and acetate infusion was not effective in perturbing the glucose-fatty acid cycle.\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: During exercise the muscle ignored the extra acetate entirely.\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. 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