title: Skeletal muscle metabolism is unaffected by DCA infusion and hyperoxia after onset of intense aerobic exercise.
abstract: This study investigated whether hyperoxic breathing (100% O(2)) or increasing oxidative substrate supply [dichloroacetate (DCA) infusion] would increase oxidative phosphorylation and reduce the reliance on substrate phosphorylation at the onset of high-intensity aerobic exercise. Eight male subjects cycled at 90% maximal O(2) uptake (VO(2 max)) for 90 s in three randomized conditions: 1) normoxic breathing and saline infusion over 1 h immediately before exercise (CON), 2) normoxic breathing and saline infusion with DCA (100 mg/kg body wt), and 3) hyperoxic breathing for 20 min at rest and during exercise and saline infusion (HYP). Muscle biopsies from the vastus lateralis were sampled at rest and after 30 and 90 s of exercise. DCA infusion increased pyruvate dehydrogenase (PDH) activation above CON and HYP (3.10 +/- 0.23, 0.56 +/- 0.08, 0.69 +/- 0.05 mmol x kg wet muscle(-1) x min(-1), respectively) and significantly increased both acetyl-CoA and acetylcarnitine (11.0 +/- 0.7, 2.0 +/- 0.5, 2.2 +/- 0.5 mmol/kg dry muscle, respectively) at rest. However, DCA and HYP did not alter phosphocreatine degradation and lactate accumulation and, therefore, the reliance on substrate phosphorylation during 30 s (CON, 51.2 +/- 5.4; DCA, 56.5 +/- 7.1; HYP, 69.5 +/- 6.3 mmol ATP/kg dry muscle) and 90 s of exercise (CON, 90.6 +/- 9.5; DCA, 107.2 +/- 13.0; HYP, 101.2 +/- 15.2 mmol ATP/kg dry muscle). These data suggest that the rate of oxidative phosphorylation at the onset of exercise at 90% VO(2 max) is not limited by oxygen availability to the active muscle or by substrate availability (metabolic inertia) at the level of PDH in aerobically trained subjects.
authors.affiliation: Department of Human Biology & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Savasi
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Evans
authors.forename: George J F
authors.initials: GJ
authors.lastname: Heigenhauser
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: Spriet
mesh_terms: D000328:Adult; D001707:Biopsy, Needle; D003999:Dichloroacetic Acid / Q000008:administration & dosage*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D015444:Exercise / Q000502:physiology*; D006801:Humans; D018496:Hyperoxia / Q000378:metabolism*; D007262:Infusions, Intravenous; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010725:Phosphocreatine / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D005082:Physical Exertion / Q000502:physiology*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D012016:Reference Values
chemical_list: D047428:Protein Kinase Inhibitors; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011768:Pyruvate Dehydrogenase Complex; D010725:Phosphocreatine; D019344:Lactic Acid; D003999:Dichloroacetic Acid; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases