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Department of Human Biology and Nutritional Sciences, University of Guelph, Ontario N1G 2W1; Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5; and Department of Physiology, The University of Melbourne, Parkville, 3052, Australia
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 µmol · min
1 · kg
wet muscle1 in trained and untrained subjects,
respectively (pH 7.0, 37°C). The sensitivity to M-CoA was greater
in trained muscle; the IC50 for M-CoA was 0.17 ± 0.04 and
0.49 ± 0.17 µM 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.
long-chain fatty acids; fatty acid transport; mitochondria; aerobic
training; 
-oxidation; carnitine palmitoyltransferase I; malonyl-coenzyme A
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