An acetyl group deficit limits mitochondrial ATP production at the onset of exercise.
The oxygen deficit at the onset of submaximal exercise represents a period when the energy demand of contraction cannot be met solely by mitochondrial ATP generation, and as a consequence there is an acceleration of ATP re-synthesis from oxygen-independent routes (phosphocreatine hydrolysis and glycolysis). Historically, the origin of the oxygen deficit has been attributed to a lag in muscle blood flow and oxygen availability at the onset of exercise which limits mitochondrial respiration. However, more recent evidence suggests that considerable inertia exists at the level of mitochondrial enzyme activation and substrate supply. In support of this latter hypothesis, we have reported on a number of occasions that pharmacological activation of the pyruvate dehydrogenase complex (and consequent stockpiling of acetyl groups), using dichloroacetate or exercise interventions, can markedly reduce the degree of ATP re-synthesis from oxygen-independent routes during the rest-to-work transition period. This review will focus on these findings, and will offer the hypothesis that acetyl group delivery to the tricarboxylic acid cycle limits mitochondrial flux at the onset of exercise--the so-called acetyl group deficit.
Greenhaff
Paul L
PL
School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, U.K. paul.greenhaff@nottingham.ac.uk
Campbell-O'Sullivan
S P
SP
Constantin-Teodosiu
D
D
Poucher
S M
SM
Roberts
P A
PA
Timmons
J A
JA
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000107:Acetylation; D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D015444:Exercise / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008931:Mitochondria, Muscle / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D005082:Physical Exertion / Q000502:physiology; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism
D011768:Pyruvate Dehydrogenase Complex; D000105:Acetyl Coenzyme A; D000255:Adenosine Triphosphate; D010100:Oxygen