Tricarboxylic acid cycle intermediate pool size and estimated cycle flux in human muscle during exercise

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  • Martin J. Gibala
    Copenhagen Muscle Research Centre, Rigshospitalet, DK-2200 Copenhagen N, Denmark; and
  • Dave A. MacLean
    Copenhagen Muscle Research Centre, Rigshospitalet, DK-2200 Copenhagen N, Denmark; and
  • Terry E. Graham
    Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1
  • Bengt Saltin
    Copenhagen Muscle Research Centre, Rigshospitalet, DK-2200 Copenhagen N, Denmark; and

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<jats:p>We examined the relationship between tricarboxylic acid (TCA) cycle intermediate (TCAI) pool size, TCA cycle flux (calculated from leg O<jats:sub>2</jats:sub>uptake), and pyruvate dehydrogenase activity (PDH<jats:sub>a</jats:sub>) in human skeletal muscle. Six males performed moderate leg extensor exercise for 10 min, followed immediately by intense exercise until exhaustion (3.8 ± 0.5 min). The sum of seven measured TCAI (ΣTCAI) increased ( P ≤ 0.05) from 1.39 ± 0.11 at rest to 2.88 ± 0.31 after 10 min and to 5.38 ± 0.31 mmol/kg dry wt at exhaustion. TCA cycle flux increased ∼70-fold during submaximal exercise and was ∼100-fold higher than rest at exhaustion. PDH<jats:sub>a</jats:sub>corresponded to 77 and 90% of TCA cycle flux during submaximal and maximal exercise, respectively. The present data demonstrate that a tremendous increase in TCA cycle flux can occur in skeletal muscle despite a relatively small change in TCAI pool size. It is suggested that the increase in ΣTCAI during exercise may primarily reflect an imbalance between the rate of pyruvate production and its rate of oxidation in the TCA cycle.</jats:p>

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