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The Journal of Experimental Biology 204, 3189-3194 (2001)
© 2001 The Company of Biologists Limited

Review

Limits to sustainable muscle performance: interaction between glycolysis and oxidative phosphorylation

Kevin E. Conley^1,2,3,*, William F. Kemper² and Gregory J. Crowther²

¹ Department of Radiology,
² Department of Physiology and Biophysics and
³ Department of Bioengineering, University of Washington Medical Center, Seattle, WA 98195-7115, USA

*Address for correspondence: Department of Radiology, Box 357115, University of Washington Medical Center, Seattle, WA 98195-7115, USA (e-mail: kconley{at}u.washington.edu)

Accepted July 2, 2001

This paper proposes a mechanism responsible for setting the sustainable level of muscle performance. Our contentions are that the sustainable work rate is determined (i) at the muscle level, (ii) by the ability to maintain ATP supply and (iii) by the products of glycolysis that may inhibit the signal for oxidative phosphorylation. We argue below that no single factor ‘limits’ sustainable performance, but rather that the flux through and the interaction between glycolysis and oxidative phosphorylation set the level of sustainable ATP supply. This argument is based on magnetic resonance spectroscopy measurements of the sources and sinks for energy in vivo in human muscle and rattlesnake tailshaker muscle during sustained contractions. These measurements show that glycolysis provides between 20% (human muscle) and 40% (tailshaker muscle) of the ATP supply during sustained contractions in these muscles. We cite evidence showing that this high glycolytic flux does not reflect an O₂ limitation or mitochondria operating at their capacity. Instead, this flux reflects a pathway independent of oxidative phosphorylation for ATP supply during aerobic exercise. The consequence of this high glycolytic flux is accumulation of H⁺, which we argue inhibits the rise in the signal activating oxidative phosphorylation, thereby restricting oxidative ATP supply to below the oxidative capacity. Thus, both glycolysis and oxidative phosphorylation play important roles in setting the highest steady-state ATP synthesis flux and thereby determine the sustainable level of work by exercising muscle.

Key words: ³¹P magnetic resonance spectroscopy, muscle, energetics, human muscle, rattlesnake.

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