Anaplerotic flux of muscle tricarboxylic acid cycle intermediates during exercise and recovery in humans

We examined changes in tricarboxylic acid cycle intermediates (TCAI) in human skeletal muscle during 5 min of dynamic knee extensor exercise (∼80% of maximum workload) and after 2 min of recovery. The total concentration of TCAI (∑TCAI) increased (P≤0.05) from 1.10±0.08 at rest to 3.12±0.24, 3.86±0.35 and 4.33±0.30 mmol·kg^-1 dry wt (dw) after 1, 3 and 5 min of exercise, respectively. The rapid increase in the ∑TCAI was primarily mediated by changes in succinate, malate, and fumarate, all of which increased (P≤0.05) by ∼250-300% after 1 min. Citrate, isocitrate, and oxaloacetate also increased (P≤0.05) during exercise, however the changes in these 3 TCAI were slower and smaller in magnitude. Following exercise most TCAI tended to decline, however citrate increased (P≤0.05) markedly and the ∑TCAI after 2 min of recovery (3.74±0.30mmol·kg^-1 dw) was not different compared to 5 min of exercise. It is concluded that (1) the ∑TCAI increases ∼2-fold within 1 min of submaximal exercise in humans; (2) the rate of pool expansion (∼2.03 mmol·(kg dw)^-1·min^-1) is substantially higher than previously suggested for human or rodent skeletal muscle; and (3) the large increase in citrate during recovery may serve to inhibit citrate synthase activity and reduce cycle flux.