HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 544/2/591    most recent 2002.021097v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Roberts, P. A. Articles by Greenhaff, P. L. Search for Related Content PubMed PubMed Citation Articles by Roberts, P. A. Articles by Greenhaff, P. L.

The acetyl group deficit at the onset of contraction in ischaemic canine skeletal muscle

Paul A. Roberts, Susan J. G. Loxham*, Simon M. Poucher*, Dumitru Constantin-Teodosiu and Paul L. Greenhaff

Considerable debate surrounds the identity of the precise cellular site(s) of inertia that limit the contribution of mitochondrial ATP resynthesis towards a step increase in workload at the onset of muscular contraction. By detailing the relationship between canine gracilis muscle energy metabolism and contractile function during constant-flow ischaemia, in the absence (control) and presence of pyruvate dehydrogenase complex activation by dichloroacetate, the present study examined whether there is a period at the onset of contraction when acetyl-coenzyme A (acetyl-CoA) availability limits mitochondrial ATP resynthesis, i.e. whether a limitation in mitochondrial acetyl group provision exists. Secondly, assuming it does exist, we also aimed to identify the mechanism by which dichloroacetate overcomes this 'acetyl group deficit'. No increase in pyruvate dehydrogenase complex activation or acetyl group availability occurred during the first 20 s of contraction in the control condition, with strong trends for both acetyl-CoA and acetylcarnitine to actually decline (indicating the existence of an acetyl group deficit). Dichloroacetate increased resting pyruvate dehydrogenase complex activation, acetyl-CoA and acetylcarnitine by ~20-fold (P < 0.01), ~3-fold (P < 0.01) and ~4-fold (P < 0.01), respectively, and overcame the acetyl group deficit at the onset of contraction. As a consequence, the reliance upon non-oxidative ATP resynthesis was reduced by ~40 % (P < 0.01) and tension development was increased by ~20 % (P < 0.05) following 5 min of contraction. The present study has demonstrated, for the first time, the existence of an acetyl group deficit at the onset of contraction and has confirmed the metabolic and functional benefits to be gained from overcoming this inertia.

This article has been cited by other articles:

				L. D. Calvert, R. Shelley, S. J. Singh, P. L. Greenhaff, J. Bankart, M. D. Morgan, and M. C. Steiner Dichloroacetate Enhances Performance and Reduces Blood Lactate during Maximal Cycle Exercise in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., May 15, 2008; 177(10): 1090 - 1094. [Abstract] [Full Text] [PDF]

				B. J. Gurd, S. J. Peters, G. J. F. Heigenhauser, P. J. LeBlanc, T. J. Doherty, D. H. Paterson, and J. M. Kowalchuk O2 uptake kinetics, pyruvate dehydrogenase activity, and muscle deoxygenation in young and older adults during the transition to moderate-intensity exercise Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R577 - R584. [Abstract] [Full Text] [PDF]

				F. B. Stephens, D. Constantin-Teodosiu, and P. L. Greenhaff New insights concerning the role of carnitine in the regulation of fuel metabolism in skeletal muscle J. Physiol., June 1, 2007; 581(2): 431 - 444. [Abstract] [Full Text] [PDF]

				B. J. Gurd, S. J. Peters, G. J. F. Heigenhauser, P. J. LeBlanc, T. J. Doherty, D. H. Paterson, and J. M. Kowalchuk Prior heavy exercise elevates pyruvate dehydrogenase activity and speeds O2 uptake kinetics during subsequent moderate-intensity exercise in healthy young adults J. Physiol., December 15, 2006; 577(3): 985 - 996. [Abstract] [Full Text] [PDF]

				P. A. Roberts, S. J. G. Loxham, S. M. Poucher, D. Constantin-Teodosiu, and P. L. Greenhaff Acetyl-CoA provision and the acetyl group deficit at the onset of contraction in ischemic canine skeletal muscle Am J Physiol Endocrinol Metab, February 1, 2005; 288(2): E327 - E334. [Abstract] [Full Text] [PDF]

				J. A Timmons, D. Constantin-Teodosiu, S. M Poucher, and P. L Greenhaff Acetyl group availability influences phosphocreatine degradation even during intense muscle contraction J. Physiol., December 15, 2004; 561(3): 851 - 859. [Abstract] [Full Text] [PDF]

				H. B. Rossiter, S. A. Ward, F. A. Howe, D. M. Wood, J. M. Kowalchuk, J. R. Griffiths, and B. J. Whipp Effects of dichloroacetate on VO2 and intramuscular 31P metabolite kinetics during high-intensity exercise in humans J Appl Physiol, September 1, 2003; 95(3): 1105 - 1115. [Abstract] [Full Text] [PDF]