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

We examined the relationship between TCA cycle intermediate pool size and TCA cycle flux (estimated from muscle oxygen uptake) in human skeletal muscle. Six males performed dynamic knee extensor exercise for 10 min at ∼60% of maximum, followed immediately by work at 100% of maximum (77±2 W) until fatigue (Exh; 3.8±05 min). The total concentration of 7 measured intermediates (ΣTCAI) increased (P≤0.05) from 1.39±0.11 at rest to 2.85±0.34 and 2.88±0.31 mmol·kg^-1 dry wt (dw) after 5 and 10 min of exercise, and increased (P≤0.05) further to 5.38±0.31 mmol·kg^-1 dw at Exh. Muscle [pyruvate] also increased (P≤0.05) progressively from 0.24±0.02 at rest to 0.38±0.02 after 5 min, and to 0.54±0.08 mmol·kg^-1 dw at Exh. TCA cycle flux increased (P≤0.05) 70-fold above rest during submaximal exercise, and was 100-fold greater than rest at Exh. The rate of flux was positively correlated with, and appeared curvilinearly related to, changes in ΣTCAI (r=0.77; P≤0.05). These data indicate that a tremendous increase in TCA cycle flux can occur despite a relatively small change in ΣTCAI. It is suggested that the increase in TCAI during exercise primarily represents an imbalance between glycolytic flux and the oxidation of pyruvate-derived acetyl CoA in the TCA cycle.