PDC activity and acetyl group accumulation in skeletal muscle during prolonged exercise

Abstract

Seven subjects cycled to exhaustion [58 +/- 7 (SE) min] at approximately 75% of their maximal oxygen uptake (VO2max). Needle biopsy samples were taken from the quadriceps femoris muscle at rest, after 3, 10, and 40 min of exercise, at exhaustion, and after 10 min of recovery. After 3 min of exercise, a nearly complete transformation of the pyruvate dehydrogenase complex (PDC) into active form had occurred and was maintained throughout the exercise period. The total in vitro activated PDC was unchanged during exercise. The muscle concentration of acetyl-CoA increased from a resting value of 8.4 +/- 1.0 to 31.6 +/- 3.3 mumol/kg dry wt at exhaustion and that of acetylcarnitine from 2.9 +/- 0.7 to 15.6 +/- 1.6 mmol/kg dry wt. This was accompanied by corresponding decreases in reduced CoA (CoASH) from 45.3 +/- 3.1 to 25.9 +/- 3.1 mumol/kg dry wt and in free carnitine from 18.8 +/- 0.7 to 5.7 +/- 0.5 mmol/kg dry wt. Acetyl group accumulation, in the form of acetyl-CoA and acetylcarnitine, was maintained throughout exercise to exhaustion while the glycogen content decreased by 90%. This suggests that availability of acetyl groups was not limiting to exercise performance despite the nearly total depletion of the glycogen store. The increased acetyl-CoA-to-CoASH ratio during exercise caused inhibition of neither the PDC transformation nor the calculated catalytic activity of active PDC.

Carbohydrate ingestion prior to exercise augments the exercise-induced activation of the pyruvate dehydrogenase complex in human skeletal muscle

“…The PDC controls the rate-limiting step in CHO oxidation, the oxidative decarboxylation of pyruvate to acetyl-CoA. The activity of PDC increases during exercise (Constantin-Teodosiu et al 1992), resulting in an increase in pyruvate flux, the formation of acetyl-CoA and a concomitant increase in CHO oxidation. When the rate of acetyl-CoA formation by the PDC exceeds its rate of oxidation by the TCA cycle, the excess acetyl-CoA is buffered by carnitine, resulting in the formation of acetylcarnitine (Constantin-Teodosiu et al 1992).…”

“…The activity of PDC increases during exercise (Constantin-Teodosiu et al 1992), resulting in an increase in pyruvate flux, the formation of acetyl-CoA and a concomitant increase in CHO oxidation. When the rate of acetyl-CoA formation by the PDC exceeds its rate of oxidation by the TCA cycle, the excess acetyl-CoA is buffered by carnitine, resulting in the formation of acetylcarnitine (Constantin-Teodosiu et al 1992). However, at the onset of exercise there is a delay in the activation of PDC and provision of acetyl groups to the TCA cycle which seems to be responsible for the increased contribution of substrate level phosphorylation to energy metabolism (Timmons et al 1997;Howlett et al 1999).…”

Skeletal muscle energy metabolism during prolonged, fatiguing exercise

“…A significant correlation (r ϭ 0.95; P Ͻ 0.05) was observed between exercise time and glycogen use, indicating that glycogen availability is a limiting factor during prolonged exercise below LT. However, because TAN was not reduced, PCr was not depleted, and no correlation was observed between glycogen content and IMP when glycogen stores were compromised, fatigue may be related to processes other than those involved in muscle high-energy phosphagen metabolism.total adenine nucleotides; phosphocreatine; lactate threshold; glycogen IT IS WELL ESTABLISHED that fatigue during prolonged exercise coincides with low intramuscular glycogen stores (2,3,9,12,13,25,32,34,38). Although there are several possible reasons as to the requirement for carbohydrate in the maintenance of contractile force (for review, see Ref.…”

Carnitine and Fat Oxidation

“…For example, during high intensity endurance exercise the rate of acetylCoA formation from PDC flux is in excess of its utilisation by the tricarboxylic acid (TCA) cycle leading to its subsequent accumulation. Another role of carnitine in skeletal muscle is to buffer the excess acetyl groups formed, in a reaction catalysed by carnitine acetyltransferase (CAT), to ensure that a viable pool of CoASH is maintained for the continuation of the PDC and TCA cycle reactions [19,20,21,22]. Indeed, following a few minutes of high intensity exercise the increase in acetylcarnitine formation is directly related to an increase in muscle acetyl-CoA [21].…”

“…Open circles are a review of results taken from [17,19,20,21,22,24] under standard conditions. Closed circles are results from [17,24] after the muscle free carnitine pool has been manipulated by 6 months of L-carnitine and carbohydrate feeding [24] or at 65% VO 2 max by reducing glycolytic flux [17] -these interventions shift the rate of fat oxidation curve up, rather than to the right.…”