Tricarboxylic acid cycle intermediates accumulate at the onset of intense exercise in man but are not essential for the increase in muscle oxygen uptake

It was proposed that a contraction-induced increase in tricarboxylic acid cycle intermediates (TCAI) is obligatory for the increase in muscle oxygen uptake at the start of exercise. To test this hypothesis, we measured changes in muscle TCAI during the initial seconds of intense exercise and used dichloroacetate (DCA) in an attempt to alter the level of TCAI. Five men performed strenuous leg kicking exercise (64±8 W) under noninfused control (CON) and DCA-supplemented conditions; biopsies (vastus lateralis) were obtained at rest and after 5, 15, and 180 s of exercise. In CON, the total concentration of three measured TCAI (ΣTCAI: citrate, malate, and fumarate) increased (p<0.05) by 71% during the first 15 s of exercise. The ΣTCAI was lower (p<0.05) in DCA than in CON at rest [0.18±0.02 vs 0.64±0.09 mmol kg−1 dry weight (d.w.)], after 5 s (0.30±0.07 vs 0.85±0.14 mmol kg−1 d.w.), and 15 s of exercise (0.60±0.07 vs 1.09±0.16 mmol kg−1 d.w.), but not different after 3 min (3.12±0.53 vs 3.23±0.55 mmol kg−1 d.w.). Despite differences in the level of muscle TCAI, muscle phosphocreatine degradation was similar in DCA and CON during the first 15 s of exercise (17.5±3.3 vs 25.6±4.1 mmol kg−1 d.w.). Taken together with our previous observation that DCA does not alter muscle oxygen uptake during the initial phase of intense leg kicking exercise (Bangsbo et al. Am J Physiol 282:R273–R280, 2002), the present data suggest that muscle TCAI accumulate during the initial seconds of exercise; however, this increase is not essential for the contraction-induced increase in mitochondrial respiration.