Muscle acetyl group availability is a major determinant of oxygen deficit in humans during submaximal exercise.
The delay in skeletal muscle mitochondrial ATP production at the onset of exercise is thought to be a function of a limited oxygen supply. The delay, termed the oxygen deficit, can be quantified by assessing the above baseline oxygen consumption during the first few minutes of recovery from exercise. During submaximal exercise, the oxygen deficit is reflected by the extent of muscle phosphocreatine (PCr) breakdown. In the present study, nine male subjects performed 8 min of submaximal, single leg knee extension exercise after saline (Control) and dichloroacetate (DCA) infusion on two separate occasions. Administration of DCA increased resting skeletal muscle pyruvate dehydrogenase complex activation status threefold (Control = 0.4 +/- 0.1 vs. DCA = 1.3 +/- 0.1 mmol acetyl-CoA.min-1.kg wet muscle-1 at 37 degrees C, P < 0.01) and elevated acetylcarnitine concentration fivefold (Control = 2.2 +/- 0.5 vs. DCA = 10.9 +/- 1.2 mmol/kg dry mass, P < 0.01). During exercise, PCr degradation was reduced by approximately 50% after DCA (Control = 33.2 +/- 7.1 vs. DCA = 18.4 +/- 7.1 mmol/kg dry mass, P < 0.05). It would appear, therefore, that in humans acetyl group availability is a major determinant of the rate of increase in mitochondrial respiration at the onset of exercise and hence the oxygen deficit.
Timmons
J A
JA
Department of Physiology and Pharmacology, University Medical School, Queen's Medical Centre, Nottingham, United Kingdom.
Gustafsson
T
T
Sundberg
C J
CJ
Jansson
E
E
Greenhaff
P L
PL
D000107:Acetylation; D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003999:Dichloroacetic Acid / Q000378:metabolism; D004789:Enzyme Activation; D015444:Exercise / Q000502:physiology*; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology*; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*
D001786:Blood Glucose; D011768:Pyruvate Dehydrogenase Complex; D010725:Phosphocreatine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D003999:Dichloroacetic Acid