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SUMMARY: ABSTRACT MYBURGH, K. H. Can Any Metabolites Partially Alleviate Fatigue Manifestations at the Cross-Bridge? Med. Sci. Sports Exerc., Vol. 36, No. 1, pp. 20-27, 2004. During exercise, intracellular homeostasis depends on the matching of adenosine triphosphate (ATP) supply and ATP demand. Metabolites play a useful role in communicating the extent of ATP demand to the metabolic supply pathways. During fatigue from high-intensity exercise, a major change in the intracellular milieu of skeletal muscle is not ATP depletion but metabolite accumulation that affects the actomyosin cross-bridge interaction. The resulting reduction in myosin ATPase activity, cross-bridge turnover rate, and velocity of contraction can be considered a useful downregulation of ATP demand. Although maximal force is reduced, it is reduced less than myosin ATPase activity. In combination, efficiency of force production at the cross-bridge is thus enhanced. This is a second useful role for metabolites during fatigue because the total ATP cost per unit of force is partially reduced. Theoretical models predict that ADP may alleviate some effects of fatigue by further enhancing cross-bridge efficiency, thus providing a third useful role for metabolite accumulation. Recent experimental evidence reviewed here suggests that this occurs when ATP concentration is dramatically reduced. Single-fiber chemical analyses of fatigued muscle show lower ATP concentrations than other methods, but whether the appropriate microenvironments for effective competition by ADP for the nucleotide binding site occur around some or all of the cross-bridges remains technically difficult to prove at this time. During fatigue, muscle activation is also decreased, a response that potentially has the greatest effect on ATP demand-supply matching. I propose that the mismatch between the expected force production relative to muscle activation and the reduced force production from inorganic phosphate accumulation is the peripheral signal for reduced activation and is therefore the fourth useful role of metabolites in alleviating fatigue. [ABSTRACT FROM AUTHOR]

SUMMARY: ABSTRACT MYBURGH, K. H. Protecting Muscle ATP: Positive Roles for Peripheral Defense Mechanisms-Introduction. Med. Sci. Sports Exerc., Vol. 36, No. 1, pp. 16-19, 2004. Skeletal muscle has evolved an impressive array of mechanisms for peripherally mediated control of ATP homeostasis. Some of these mechanisms are intracellular, and others are extracellular and include influences on the cross-bridge cycle itself and substrate supply. This paper introduces three distinctly different topics that nevertheless all have ATP defense in common. The role of ADP in fatigue is controversial but has recently been more clearly delineated so that an effect on alleviating force declines during extreme fatigue is plausible. AMP plays its role by activating the protein-kinase, AMPK, which is a key sensor of cellular energy stress. AMPK has different isoforms, is not uniformly distributed in the cell, and its activation is carefully controlled. It has multiple effects including improvements in substrate supply for the metabolic pathways producing ATP and inhibition of anabolic processes to further spare ATP. Red blood cells have the capacity to sense hypoxia and to release vasodilators where there is a locally increased demand for blood supply. The papers in this series emphasize the important positive roles of metabolites and sensors of fatigue in the balance between ATP supply and demand. [ABSTRACT FROM AUTHOR]