Dissociation between muscle tricarboxylic acid cycle pool size and aerobic energy provision during prolonged exercise in humans

It has been suggested that a decrease in the total concentration of tricarboxylic acid cycle intermediates (TCAIs) ‐ secondary to a reduction in glycogen availability ‐ compromises oxidative energy provision in skeletal muscle during prolonged exercise. However, no study has directly tested this hypothesis. We therefore studied six men (28 ± 2 years) during 90 min of leg kicking exercise at an intensity equivalent to 70 % of maximum. Biopsies (vastus lateralis) were obtained at rest and after 5, 10, 15, 30, 60 and 90 min of exercise, and thigh oxygen uptake ( V O2,thigh ) was calculated according to the Fick principle. The sum of six measured TCAIs (≈95 % of total pool size) was 1.30 ± 0.15 mmol (kg dry wt) −1 at rest and increased ( P ≤ 0.05 ) rapidly during exercise to a peak value of 3.15 ± 0.23 mmol (kg dry wt) −1 after 10 min. Thereafter, the [TCAI] declined to 2.14 ± 0.23, 1.73 ± 0.32 and 1.62 ± 0.10 mmol (kg dry wt) −1 after 30, 60 and 90 min, respectively ( P ≤ 0.05 vs. 10 min). Despite the 50 % decrease in [TCAI], aerobic energy provision was not compromised, as evidenced by stable V O2 ,thigh values throughout the entire exercise bout and little change in muscle [phosphocreatine] after 10 min. The largest decrease in [TCAI] (Δ+ 1.00 ± 0.24 mmol (kg dry wt) −1 ) occurred from 10 to 30 min of exercise despite the fact that muscle [glycogen] remained relatively high at this point in exercise (≈274 ± 24 mmol (kg dry wt) −1 after 30 min; ≈65 % of rest value). Conversely, there was little change in [TCAI] during the final 30 min of exercise (Δ+ 0.11 ± 0.29 mmol (kg dry wt) −1 ) despite a decrease in [glycogen] to ≈72 ± 3 mmol (kg dry wt) −1 after 90 min (≈13 % of rest value). We conclude that there is a progressive decrease in muscle [TCAI] during prolonged exercise in humans; however this decrease does not compromise aerobic energy provision and is not attributable to the depletion of muscle [glycogen].