Effect of short-term training on mitochondrial ATP production rate in human skeletal muscle

Seven untrainedvolunteers [3 men, 4 women, 20.1 ± 2.0 (SD) yr, 66.0 ± 11.0 kg, 171 ± 13 cm] participated in a 10-day cycle exercisetraining program. Resting muscle samples were obtained from vastuslateralis before and after 5 and 10 days of training. Mitochondrial ATPproduction rate (MAPR) was assayed in isolated mitochondria by using abioluminescence technique and referenced to the activity of glutamatedehydrogenase in the muscle sample. MAPR increased 136 and 161% after10 days of training for the mitochondrial substrate combinationspyruvate + palmitoyl-L-carnitine + -ketoglutarate + malate andpalmitoyl-L-carnitine + malate, respectively. Total muscle glutamate dehydrogenase and citrate synthaseactivity increased 53 and 16%, respectively, after 5 days but did notsignificantly increase further after 10 days. The results from thepresent study indicate that MAPR, measured by using the substratecombinations pyruvate + palmitoyl-L-carnitine + -ketoglutarate + malate andpalmitoyl-L-carnitine + malate, can rapidly increase in response to endurance training.     

Sensitivity of CPT I to malonyl-CoA in trained and untrained human skeletal muscle

The present study examined the sensitivity of carnitine palmitoyltransferase I (CPT I) activity to its inhibitor malonyl-CoA (M-CoA), and simulated metabolic conditions of rest and exercise, in aerobically trained and untrained humans. Maximal CPT I activity was measured in mitochondria isolated from resting human skeletal muscle. Mean CPT I activity was 492.8 +/- 72.8 and 260.8 +/- 33.6 micromol. min(-1). kg wet muscle(-1) in trained and untrained subjects, respectively (pH 7.0, 37 degrees C). The sensitivity to M-CoA was greater in trained muscle; the IC(50) for M-CoA was 0.17 +/- 0.04 and 0.49 +/- 0.17 microM in trained and untrained muscle, respectively. The presence of acetyl-CoA, free coenzyme A (CoASH), and acetylcarnitine, in concentrations simulating rest and exercise conditions did not release the M-CoA-induced inhibition of CPT I activity. However, CPT I activity was reduced at pH 6.8 vs. pH 7.0 in both trained and untrained muscle in the presence of physiological concentrations of M-CoA. The results of this study indicate that aerobic training is associated with an increase in the sensitivity of CPT I to M-CoA. Accumulations of acetyl-CoA, CoASH, and acetylcarnitine do not counteract the M-CoA-induced inhibition of CPT I activity. However, small decreases in pH produce large reductions in the activity of CPT I and may contribute to the decrease in fat metabolism that occurs during moderate and intense aerobic exercise intensities.