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Cellular Processes Integrating the Metabolic Response to Exercise

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Abstract

The sections in this article are:

1 The Central Role of Adenine Nucleotides
1.1 Components of the High‐Energy Phosphate System
1.2 Phosphate Metabolites are a Linked Network
2 Approaches to Understanding Metabolic Control
2.1 Classic Enzyme Kinetics
2.2 Nonequilibrium Thermodynamics
2.3 Regulated Enzymes and the Role of Calcium
3 Determinants of Muscle Cell ATPase Rate
3.1 The Basal ATPase
3.2 The Contractile ATPase
4 Metabolite Changes During Muscle Stimulation
4.1 Methodology
4.2 The Low‐Rate, Nonfatiguing Domain
4.3 The High‐Rate, Fatiguing Domain
4.4 The Transitional Domain
5 Control of Oxidative Phosphorylation in Muscle
5.1 Kinetic Control by [ADP]
5.2 Thermodynamic Control by Cytoplasmic Phosphates
5.3 Experimental Tests of Control Models
5.4 The Importance of Muscle Aerobic Capacity
6 Control of Glycogenolysis/Glycolysis in Muscle
6.1 The Conventional View
6.2 Problems with the Conventional View
6.3 Reaction Disequilibria and Metabolite Diffusion
6.4 Enzyme Organization
7 Control of Force Generation
8 Summary and Future Directions
Figure 1. Figure 1.

Schematic illustrating the key roles of calcium and phosphate metabolites in regulating force and ATP production in skeletal muscle.

Figure 2. Figure 2.

A, Calculated changes in normalized metabolite levels as a function of high‐energy phosphate depletion assuming constant pH = 7. PCr is normalized as a fraction of the total creatine pool (TCr), adenine nucleotides as fractions of the total adenine nucleotide pool (TAN), and high‐energy phosphate (PCr + 2ATP + ADP) as a fraction of (TCr + 2TAN). [Recalculated from Connett 26.] B, Changes in ΔGATP as a function of high‐energy phosphate depletion, assuming constant pH = 7, TCr = 40 mM, TAN = 10 mM, and Pi = 0 at PCr/TCr = 1.

Figure 3. Figure 3.

A, Dependence of the net reaction rate of an enzyme‐catalyzed reaction on substrate concentration, [S], assuming classic Michaelis‐Menton kinetics with Kms = 0.5 mM, and [P] = 0. B, Dependence of net reaction rate on substrate concentration assuming Keq = 1, Kms = 0.5 mM, Kmp = 1 mM, and [P] = 1 mM. C, Dependence of net reaction rate on reaction affinity, assuming Keq = 100, Kms = 0.5 mM, Kmp = 1 mM, [S] + [P] = 10 mM.

Figure 4. Figure 4.

Schematic illustrating some important features of excitation‐contraction coupling and calcium cy cling in skeletal muscle. DHP‐R, dihy dropyridine‐sensitive voltage‐gated calcium channel; RY‐R, ryanodine‐sensitive SR calcium release channel; SERCA, sarcoplasmic/endoplasmic reticulum calcium ATPase.

Figure 5. Figure 5.

High‐energy phosphate utilization (∼P) as a function of tetanus tension–time integral in mouse soleus and EDL muscle at 20°C.

From Crow and Kushmerick 31
Figure 6. Figure 6.

A, Time course of PCr changes in rat gastrocnemius muscle during and after nonfatiguing twitch stimulation. [From Meyer 117.] B, Relationship between steady‐state PCr and oxygen consumption in rat gastrocnemius muscle during nonfatiguing stimulation. [From Meyer 117.] C, Relationship between time constant for PCr changes (τ) and muscle total creatine content. Total creatine content of rat gastrocnemius muscle was depleted by 2 or 4 weeks feeding the creatine analog, β‐guanidinopropionate. [From Meyer 118.] D, Relationship between rate constant for PCr recovery (1/τ) and muscle mitochondrial content. Mitochondrial content of rat gastrocnemius muscle was increased by endurance training (10 weeks' duration, 1 h/day on a running wheel, final mean speed 38 m/min). Mitochondrial content was decreased by chemical thyroidectomy (0.025% methiamizole in drinking water for 8 weeks).

From Paganini, Foley, and Meyer, unpublished observations
Figure 7. Figure 7.

Time course of changes in peak twitch force (A), PCr (B), ATP (C), and intracellular pH (D) during fatiguing (5 Hz) stimulation. PCr, ATP, and pH measured by 31P‐NMR as described in Meyer et al. 120.

From Paganini and Meyer, unpublished observations
Figure 8. Figure 8.

Schematic illustrating main features of mitochondrial oxidative phosphorylation.

Figure 9. Figure 9.

A, Steady‐state as a function of stimulation rate in cat soleus muscles perfused at 37°C with red cell suspension in Krebs‐Hensleit solution equilibrated with 5% CO2 (perfusate pH 7.4) and 70% CO2 (perfusate pH 6.7). Intracellular pH was 7.1 and 6.5, respectively. B, Relationship between steady‐state PCr and in cat soleus muscles during normocapnic and hypercapnic perfusion. C, Relationship between steady‐state calculated [ADP] and .

From Harkema and Meyer 65
Figure 10. Figure 10.

Parallel dose‐dependent effects of perfusion with my‐xothiazol on peak and NADH–cytochrome reductase activity in rat hindlimb muscle.

From McAllister and Terjung 112
Figure 11. Figure 11.

Schematic illustrating important control points in muscle glycogenolysis and glycolysis.

Figure 12. Figure 12.

Top, Kinetic model for the creatine kinase reaction 130. The assumed equilibrium constants for the depicted substrate binding reactions are given in mM. The rate constants kt and kr were selected so that model yielded equilibrium unidirectional fluxes of 10 mM/s for [ATP] = 10 mM, [PCr] = 36 mM, and [Cr] = 10 mM. pH was held constant at 7. ADP changes during tetani and twitches were computed by Euler's method (dt = 10 μs) assuming step changes in ATPase rate, Q. Bottom, Calculated [ADP] during tetanic and twitch contractions using the above model with high and low initial [PCr]/[Cr] ratio. Total phosphagen use was assumed to be 1.5 mM and 0.3 mM for single tetani and twitches, respectively 49,75. Solid lines are [ADP] calculated from the kinetic model, and dashed lines are [ADP] calculated from the same PCr levels assuming instantaneous equilibrium of the net creatine kinase re action.

Figure 13. Figure 13.

Calculated drop in ΔGATP at the center of a cylinder in which ATP is consumed at a constant, steady‐state rate (Q = 1 mM/s), as a function of cylinder radius, and in the presence or absence of the creatine kinase reaction at equilibrium (Keq = 1.66 × 109 M−1, pH 7). Metabolites outside the cylinder were assumed to be constant at the indicated levels. Diffusion coefficients of Pi, adenine nucleotides, and PCr and creatine were assumed to be 3 × 10−6, 1 × 10−6, and 2 × 10−6 cm2/s, respectively 125. Even over the dimensions of a large cyclindrical cell (radius 30 μm) the creatine kinase reaction virtually abolishes any radial gradient in ΔGATP.

Figure 14. Figure 14.

Relationship between intracellular pH and peak tetanic force during repetitive tetanic stimulation (open circles) and during perfusion with hypercapnic media (closed), in cat biceps brachii (top) and soleus (bottom) muscles.

From Adams et al. (1


Figure 1.

Schematic illustrating the key roles of calcium and phosphate metabolites in regulating force and ATP production in skeletal muscle.



Figure 2.

A, Calculated changes in normalized metabolite levels as a function of high‐energy phosphate depletion assuming constant pH = 7. PCr is normalized as a fraction of the total creatine pool (TCr), adenine nucleotides as fractions of the total adenine nucleotide pool (TAN), and high‐energy phosphate (PCr + 2ATP + ADP) as a fraction of (TCr + 2TAN). [Recalculated from Connett 26.] B, Changes in ΔGATP as a function of high‐energy phosphate depletion, assuming constant pH = 7, TCr = 40 mM, TAN = 10 mM, and Pi = 0 at PCr/TCr = 1.



Figure 3.

A, Dependence of the net reaction rate of an enzyme‐catalyzed reaction on substrate concentration, [S], assuming classic Michaelis‐Menton kinetics with Kms = 0.5 mM, and [P] = 0. B, Dependence of net reaction rate on substrate concentration assuming Keq = 1, Kms = 0.5 mM, Kmp = 1 mM, and [P] = 1 mM. C, Dependence of net reaction rate on reaction affinity, assuming Keq = 100, Kms = 0.5 mM, Kmp = 1 mM, [S] + [P] = 10 mM.



Figure 4.

Schematic illustrating some important features of excitation‐contraction coupling and calcium cy cling in skeletal muscle. DHP‐R, dihy dropyridine‐sensitive voltage‐gated calcium channel; RY‐R, ryanodine‐sensitive SR calcium release channel; SERCA, sarcoplasmic/endoplasmic reticulum calcium ATPase.



Figure 5.

High‐energy phosphate utilization (∼P) as a function of tetanus tension–time integral in mouse soleus and EDL muscle at 20°C.

From Crow and Kushmerick 31


Figure 6.

A, Time course of PCr changes in rat gastrocnemius muscle during and after nonfatiguing twitch stimulation. [From Meyer 117.] B, Relationship between steady‐state PCr and oxygen consumption in rat gastrocnemius muscle during nonfatiguing stimulation. [From Meyer 117.] C, Relationship between time constant for PCr changes (τ) and muscle total creatine content. Total creatine content of rat gastrocnemius muscle was depleted by 2 or 4 weeks feeding the creatine analog, β‐guanidinopropionate. [From Meyer 118.] D, Relationship between rate constant for PCr recovery (1/τ) and muscle mitochondrial content. Mitochondrial content of rat gastrocnemius muscle was increased by endurance training (10 weeks' duration, 1 h/day on a running wheel, final mean speed 38 m/min). Mitochondrial content was decreased by chemical thyroidectomy (0.025% methiamizole in drinking water for 8 weeks).

From Paganini, Foley, and Meyer, unpublished observations


Figure 7.

Time course of changes in peak twitch force (A), PCr (B), ATP (C), and intracellular pH (D) during fatiguing (5 Hz) stimulation. PCr, ATP, and pH measured by 31P‐NMR as described in Meyer et al. 120.

From Paganini and Meyer, unpublished observations


Figure 8.

Schematic illustrating main features of mitochondrial oxidative phosphorylation.



Figure 9.

A, Steady‐state as a function of stimulation rate in cat soleus muscles perfused at 37°C with red cell suspension in Krebs‐Hensleit solution equilibrated with 5% CO2 (perfusate pH 7.4) and 70% CO2 (perfusate pH 6.7). Intracellular pH was 7.1 and 6.5, respectively. B, Relationship between steady‐state PCr and in cat soleus muscles during normocapnic and hypercapnic perfusion. C, Relationship between steady‐state calculated [ADP] and .

From Harkema and Meyer 65


Figure 10.

Parallel dose‐dependent effects of perfusion with my‐xothiazol on peak and NADH–cytochrome reductase activity in rat hindlimb muscle.

From McAllister and Terjung 112


Figure 11.

Schematic illustrating important control points in muscle glycogenolysis and glycolysis.



Figure 12.

Top, Kinetic model for the creatine kinase reaction 130. The assumed equilibrium constants for the depicted substrate binding reactions are given in mM. The rate constants kt and kr were selected so that model yielded equilibrium unidirectional fluxes of 10 mM/s for [ATP] = 10 mM, [PCr] = 36 mM, and [Cr] = 10 mM. pH was held constant at 7. ADP changes during tetani and twitches were computed by Euler's method (dt = 10 μs) assuming step changes in ATPase rate, Q. Bottom, Calculated [ADP] during tetanic and twitch contractions using the above model with high and low initial [PCr]/[Cr] ratio. Total phosphagen use was assumed to be 1.5 mM and 0.3 mM for single tetani and twitches, respectively 49,75. Solid lines are [ADP] calculated from the kinetic model, and dashed lines are [ADP] calculated from the same PCr levels assuming instantaneous equilibrium of the net creatine kinase re action.



Figure 13.

Calculated drop in ΔGATP at the center of a cylinder in which ATP is consumed at a constant, steady‐state rate (Q = 1 mM/s), as a function of cylinder radius, and in the presence or absence of the creatine kinase reaction at equilibrium (Keq = 1.66 × 109 M−1, pH 7). Metabolites outside the cylinder were assumed to be constant at the indicated levels. Diffusion coefficients of Pi, adenine nucleotides, and PCr and creatine were assumed to be 3 × 10−6, 1 × 10−6, and 2 × 10−6 cm2/s, respectively 125. Even over the dimensions of a large cyclindrical cell (radius 30 μm) the creatine kinase reaction virtually abolishes any radial gradient in ΔGATP.



Figure 14.

Relationship between intracellular pH and peak tetanic force during repetitive tetanic stimulation (open circles) and during perfusion with hypercapnic media (closed), in cat biceps brachii (top) and soleus (bottom) muscles.

From Adams et al. (1
References
 1. Adams, G. R., M. J. Fisher, and R. A. Meyer. Hypercapnic acidosis and increased H2PO4‐ concentration do not decrease force in cat skeletal muscle. Am. J. Physiol. 260 (Cell Physiol. 29): C805–C812, 1991.
 2. Adams, G. R., J. M. Foley, and R. A. Meyer. Muscle buffer capacity estimated from pH changes during rest‐to‐work transitions. J. Appl. Physiol. 69: 968–972, 1990.
 3. Alberty, R. A. Effect of pH and metal ion concentration on the equilibrium hydrolysis of adenosine triphosphate to adenosine diphosphate. J. Biol. Chem. 243: 1337–1343, 1968.
 4. Aragon, J. J., K. Tornheim, and J. M. Lowenstein. On the possible role of IMP in the regulation of phosphorylase activity in skeletal muscle. FEBS Lett. 117: K56–K64, 1980.
 5. Baker, A. J., M. C. Longuemare, R. Brandes, and M. W. Weiner. Intracellular tetanic calcium signals are reduced in fatigue of whole skeletal muscle. Am. J. Physiol. 264 (Cell Physiol. 33): C577–C582, 1993.
 6. Balaban, R. S. Regulation of oxidative phosphorylation in the mammalian cell. Am. J. Physiol. 258 (Cell Physiol. 27): C377–C389, 1990.
 7. Bárány, M. ATPase activity of myosin correlated with speed of shortening. J. Gen. Physiol. 50: 197–216, 1967.
 8. Barstow, T. J., S. Buchthal, S. Zanconato, and D. M. Cooper. Muscle energetics and pulmonary O2 uptake kinetics during moderate exercise. J. Appl. Physiol. 77: 1742–1749, 1994.
 9. Benders, A., T. van Kuppevelt, A. Oseterhof, R. A. Wevers, and J. H. Veerkamp. Adenosine triphosphatases during maturation of cultured human skeletal muscle cells and in adult human muscle. Biochim. Biophys. Acta 1112: 89–98, 1992.
 10. Blinks, J. R., R. Rudel, and S. R. Taylor. Calcium transients in isolated amphibian skeletal muscle fibres: detection with aequorin. J. Physiol. (Lond.) 277: 291–323, 1978.
 11. Blum, H., M. D. Schnall, B. Chance, and G. P. Buzby. Intracellular sodium flux and high‐energy phosphorus metabolites in ischemic skeletal muscle. Am. J. Physiol. 255 (Cell Physiol. 24): C377–C384, 1988.
 12. Bockman, E. L., and J. E. McKenzie. Tissue adenosine content in active soleus and gracilis muscles of cats. Am. J. Physiol. 244 (Heart Circ. Physiol. 13): H555–H559, 1983.
 13. Boska, M. ATP production rate as a function of force level in the human gastrocnemius/soleus using 31P MRS. Magn. Reson. Med. 32: 1–10, 1994.
 14. Brand, M. D., M. E. Harper, and H. C. Taylor. Control of the effective P/O ratio of oxidative phosphorylation in liver mitochondria and hepatocytes. Biochem. J. 291: 739–748, 1993.
 15. Briggs, F. N., J. L. Poland, and R. J. Solaro. Relative capabilities of sarcoplasmic reticulum in fast and slow mammalian skeletal muscles. J. Physiol. (Lond.) 266: 587–594, 1977.
 16. Brooks, G. A. Anaerobic threshold: review of the concept and directions for future research. Med. Sci. Sports Exerc. 17: 22–34, 1985.
 17. Brooks, G. A., and J. Mercier. Balance of carbohydrate and lipid utilization during exercise: the “crossover” concept. J. Appl. Physiol. 76: 2253–2261, 1994.
 18. Brown, D. H., and C. F. Cori. Animal and plant phospho‐rylases. In: The Enzymes V, edited by P. D. Boyer, H. Lardy, and K. Myrback. New York: Academic Press, 1961, p. 207–228, 1961.
 19. Caplan, S. R., and A. Essig. Bioenergetics and Linear Non‐Equilibrium Thermodynamics: The Steady State. Cambridge, MA: Harvard University Press, 1983.
 20. Chance, B., J. S. Leigh, Jr., B. J. Clark, J. Maris, J. Kent, S. Nioka, and D. Smith. Control of oxidative metabolism and oxygen delivery in human skeletal muscle: a steady‐state analysis of the work/energy cost transfer function. Proc. Natl. Acad. Sci. U.S.A. 82: 8384–8388, 1985.
 21. Chance, B., and C. M. Williams. The respiratiory chain and oxidative phosphorylation. Adv. Enzymol. 17: 65–134, 1956.
 22. Chasiotis, D. The regulation of glycogen phosphorylase and glycogen breakdown in human skeletal muscle. Acta Physiol. Scand. Suppl. 518: 1–68, 1983.
 23. Chinet, A., T. Clausen, and L. Girardier. Microcalorimetric determination of energy expenditure due to active sodium‐potassium transport in soleus muscle and brown adipose tissue of the rat. J. Physiol. (Lond.) 256: 43–61, 1977.
 24. Close, R. Dynamic properties of mammalian skeletal muscle. Ann. Rev. Physiol. 52: 129–196, 1972.
 25. Conlee, R. K., J. A. McLane, M. J. Rennie, W. W. Winder, and J. O. Holloszy. Reversal of phosphorylase activation in muscle despite continued contractile activity. Am. J. Physiol. 237 (Regulatory Integrative Comp. Physiol. 6): R291–R296, 1979.
 26. Connett, R. J. Analysis of metabolic control: new insights using a scaled creatine kinase model. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R949–R959, 1988.
 27. Connett, R. J., E. J. Gayeski, and C. R. Honig. Lactate accumulation in fully aerobic, working dog gracilis muscle. Am. J. Physiol. 246 (Heart Circ. Physiol. 15): H120–H128, 1984.
 28. Connett, R. J., T. Gayeski, and C. R. Honig. Energy sources in fully aerobic rest‐work transitions. Am. J. Physiol. 248 (Heart Circ. Physiol. 17): H922–H929, 1985.
 29. Connett, R. J., C. R. Honig, T. E. J. Gayeski, and G. A. Brooks. Defining hypoxia: a systems view of VO2, glyco‐lyis, energetics, and intracellular PO2. J. Appl. Physiol. 68: 833–842, 1990.
 30. Cornish‐Bowden, A., and M. L. Cardenas (Eds.). Control of Metabolic Processes. NATO ASI Series A: Life Sci. 190. New York: Plenum Press, 1989.
 31. Crow, M. X., and M. J. Kushmerick. Chemical energetics of slow and fast twitch muscles of the mouse. J. Gen. Physiol. 79: 147–166, 1982.
 32. Crow, M. T., and M. J. Kushmerick. Correlated reduction of velocity of shortening and the rate of energy utilization in mouse fast‐twitch muscle during a continuous tetanus. J. Gen. Physiol. 82: 703–720, 1983.
 33. Cuenda, A., F. Centeno, and C. Gutierrez‐Merino. Modulation of phosphorylation of glycogen phosphorylase‐sarcoplasmic reticulum interaction. FEBS Lett. 283: 273–276, 1991.
 34. Curtin, N. A. Buffer power and intracellular pH of frog sartorius muscle. Biophys. J. 50: 837–841, 1986.
 35. Dawson, M. J., D. G. Gadian, and D. R. Wilkie. Mechanical relaxation rate and metabolism studied in fatiguing muscle by phosphorus nuclear magnetic resonance. J. Physiol. (Lond.) 299: 456–585, 1980.
 36. Dawson, M. J., D. G. Gadian, and D. R. Wilkie. Muscular fatigue investigated by phosphorus nuclear magnetic resonance. Nature 274: 861–866, 1978.
 37. Dudley, G. A., and R. L. Terjung. Influence of acidosis on AMP deaminase activity in contracting fast‐twitch muscle. Am. J. Physiol. 248 (Cell Physiol. 17): C43–C50, 1985.
 38. Dudley, G. A., and R. L. Terjung. Influence of aerobic metabolism on IMP accumulation in fast‐twitch muscle. Am. J. Physiol. 248 (Cell Physiol. 17): C37–C42, 1985.
 39. Dudley, G. A., P. C. Tullson, and R. L. Terjung. Influence of mitochondrial content on the sensitivity of respiratory control. J. Biol. Chem. 262: 9109–9114, 1987.
 40. Echteld, C. J. A., J. H. G. M. van Beek, J. H. Kirkels, P. van der Meer, T. J. C. Ruigrok, and N. Westerhof. 31P NMR study of the response of myocardial energy metabolism to heart rate steps. Yufuin, Japan: International Congress on Muscle Energetics: 1989.
 41. Edstrom, L., E. Hultman, K. Sahlin, and H. Sjoholm. The contents of high‐energy phosphates in different fibre types in skeletal muscles from rat, guinea‐pig, and man. J. Physiol. (Lond.) 332: 47–58, 1982.
 42. Edstrom, R. D., M. H. Meinke, M. E. Gurnack, D. M. Steinhorn, X. Yang, R. Yang, and D. F. Evans. Regulation of muscle glycogenolysis. In: Control of Metabolic Processes. NATO ASI Series A: Life Sci. 190. edited by A. Cornish‐Bowden and M. L. Cardenas. New York: Plenum Press, 1989, p. 209–217.
 43. Erecinska, M., D. F. Wilson, and K. Nishiki. Homeostatic regulation of cellular energy metabolism: experimental characterization in vivo and fit to a model. Am. J. Physiol. 234 (Cell Physiol. 3): C82–C89, 1978.
 44. Everts, M. E., J. P. Andersen, T. Clausen, and O. Hansen. Quantitative determination of Ca2+‐dependent Mg2+‐ATP‐ase from sarcoplasmic reticulum in muscle biopsies. Biochem. J. 260: 443–448, 1989.
 45. Ferguson, S. J., and M. C. Sorgato. Proton electrochemical gradients and energy transduction processes. Ann. Rev. Biochem. 51: 185–217, 1982.
 46. Fitts, R. H. Cellular mechanisms of muscle fatigue. Physiol. Rev. 74: 49–94, 1994.
 47. Foley, J. M., G. R. Adams, and R. A. Meyer. Utility of AICAr for metabolic studies is diminished by systemic effects in situ. Am. J. Physiol. 257 (Cell Physiol. 26): C488–C494, 1989.
 48. Foley, J. M., S. J. Harkema, and R. A. Meyer. Decreased ATP cost of isometric contractions in ATP‐depleted rat fast‐twitch muscle. Am. J. Physiol. 261 (Cell Physiol. 30): C872–C881, 1991.
 49. Foley, J. M., and R. A. Meyer. Energy cost of twitch and tetanic contractions of rat muscle estimated in situ by gated 31P NMR. NMR Biomed. 5: 32–38, 1993.
 50. Fruen, B. R., J. R. Michelson, N. H. Shomer, T. J. Roghair, and C. F. Louis. Regulation of the sarcoplasmic reticulum ryanodine receptor by inorganic phosphate. J. Biol. Chem. 269: 192–198, 1994.
 51. Funk, C. I., A. Clark, Jr., and R. J. Connett. A simple model of aerobic metabolism: applications to work transitions in muscle. Am. J. Physiol. 258 (Cell Physiol. 27): C995–C1005, 1990.
 52. Gadian, D. G. Nuclear Magnetic Resonance and Its Applications to Living Systems. London: Oxford University Press, 1982.
 53. Galione, A. Cyclic ADP‐ribose: a new way to control calcium. Science 259: 325–326, 1993.
 54. Garcia‐Tejedor, A. J., J. M. Riol‐Cimas, F. Morani, E. Melendez‐Hevia, and F. Montero. Transition state of the glycolytic pathway under FDP saturating conditions: experimental studies and a theoretical model. Int. J. Biochem. 20: 421–426, 1988.
 55. Gladden, L. B., W. N. Stainsby, and B. R. Macintosh. Norepinephrine increases canine skeletal muscle Vo2 during recovery. Med. Sci. Sports Exerc. 14: 471–478, 1982.
 56. Gollnick, P., and B. Saltin. Significance of skeletal muscle oxidative enzyme enhancement with endurance training. Clin. Physiol. 2: 1–12, 1992.
 57. Graham, T. E., J. K. Barclay, and B. A. Wilson. Skeletal muscle lactate release and glycolytic intermediates during hypercapnia. J. Appl. Physiol. 60: 568–575, 1986.
 58. Graham, T. E., and B. Saltin. Estimation of the mitochondrial redox state in human skeletal muscle during exercise. J. Appl. Physiol. 66: 561–566, 1989.
 59. Green, N. M. Evolutionary relationships within the family of P‐type cation pumps. Ann. N. Y. Acad. Sci. 671: 104–112, 1992.
 60. Gyulai, L., J. Z. Roth, J. S. Leigh, Jr., and B. Chance. Bioenergetic studies of mitochondrial oxidative phosphorylation using 31‐phosphorus NMR. J. Biol. Chem. 260: 3947–3954, 1985.
 61. Hak, J. B., J. H. G. M. van Beek, M. H. van Wijhe, and N. Westerhof. Influence of temperature on the response time of mitochondrial oxygen consumption in isolated rabbit heart. J. Physiol. (Lond.) 447: 17–31, 1992.
 62. Hansford, R. G. Relation between mitochondrial calcium transport and control of energy metabolism. Rev. Physiol. Biochem. Pharmacol. 102: 1–72, 1985.
 63. Hansford, R. G. Role of calcium in respiratory control. Med. Sci. Sports Exerc. 26: 44–51, 1994.
 64. Harkema, S. J., and R. A. Meyer. Control of oxidative metabolism by cytosolic phosphorylation potential in slow twitch muscle in situ. Physiologist 35: 206, 1992.
 65. Harkema, S. J., and R. A. Meyer. Evidence that ADP does not control respiration in acidotic skeletal muscle. Proceedings of the Society of Magnetic Resonance (2nd meeting), 1994, p. 358.
 66. Harris, D. A., and A. M. Das. Control of mitochondrial ATP synthesis in the heart. Biochem. J. 280: 561–573, 1991.
 67. Harris, R. C., R. H. T. Edwards, E. Hultman, and L. O. Nordesto. The time course of phosphorylcreatine resynthesis during recovery of the quadriceps muscle in man. Pflugers Arch. 367: 137–142, 1976.
 68. Hillered, L., L. Ernster, and B. K. Siesjo. Influence of in vitro lactic acidosis and hypercapnia on respiratory activity of isolated rat brain mitochondria. J. Cereb. Blood Flow Metab. 4: 430–437, 1984.
 69. Hintz, C. S., M. M.‐Y. Chi, R. D. Fell, J. L. Ivy, K. K. Kaiser, C. V. Lowry, and O. H. Lowry. Metabolite changes in individual rat muscle fibers during stimulation. Am. J. Physiol. 242 (Cell Physiol. 11): C218–C228, 1982.
 70. Hobbs, S. F., and D. I. McCloskey. Effects of blood pressure on force production in cat and human muscle. J. Appl. Physiol. 63: 834–839, 1987.
 71. Hochachka, P. W., and G. O. Matheson. Regulating ATP turnover rates over broad dynamic work ranges in skeletal muscles. J. Appl. Physiol. 73: 1697–1703, 1992.
 72. Hochachka, P. W., and T. P. Mommsen. Protons and ana‐erobiosis. Science 219: 1391–1397, 1983.
 73. Homsher, E., and C. J. Kean. Skeletal muscle energetics and metabolism. Ann. Rev. Physiol. 40: 93–131, 1978.
 74. Homsher, E., W. F. H. M. Mommaerts, N. V. Ricchiuti, and A. Wallner. Activation heat, activation metabolism and tension‐related heat in frog semitendinosis muscles. J. Physiol. (Lond.) 220: 601–625, 1972.
 75. Hood, D. A., J. Gorski, and R. L. Terjung. Oxygen cost of twitch and tetanic isometric contractions in rat skeletal muscle. Am. J. Physiol. 250 (Endocrinol. Metab. 13): E449–E456, 1986.
 76. Hood, D. A., and G. Paren. Metabolic and contractile responses of rat fast‐twitch muscle to 10–Hz stimulation. Am. J. Physiol. 260 (Cell Physiol. 29): C832–C840, 1991.
 77. Horton, E. S., and R. L. Terjung (Eds.). Exercise, Nutrition, and Energy Metabolism. New York: Macmillan Publishing Company, 1988.
 78. Hutchinson, W. L., P. G. Morris, and J. Mowbray. The molecular structure of a rapidly formed oligomeric adenosine tetraphosphate derivative from rat heart. Biochem. J. 234: 623–627, 1986.
 79. Huxley, H.E. Cross‐bridge movement and filament overlap. Biophys. J. 11: 235a, 1971.
 80. Inesi, G., and M. R. Kirtley. Structural features of cation transport ATPases. J. Bioenerg. Biomembr. 24: 271–283, 1992.
 81. Ivy, J. L., R. T. Withers, P. J. Van Handel, D. H. Elger, and D. L. Costill. Muscle respiratory capacity and fiber type as determinants of the lactate threshold. J. Appl. Physiol. 48: 523–527, 1980.
 82. Jacobus, W. E. Respiratory control and the integration of heart high‐energy phosphate metabolism by mitochondrial creatine kinase. Ann. Rev. Physiol. 47: 707–725, 1985.
 83. Jacobus, W. E., R. W. Moreadith, and K. M. Wandegaer. Mitochondrial respiratory control: evidence against the regulation of respiration by extramitochondrial phosphorylation potential or ATP/ADP ratios. J. Biol. Chem. 257: 2397–2402, 1982.
 84. Jeneson, J. A. L., H. V. Westerhoff, T. R. Brown, C. J. A. van Echteld, and R. Berger. Quasi‐linear relationship between Gibbs free energy of ATP hydrolysis and power‐output in human forearm muscle. Am. J. Physiol. 268 (Cell Physiol. 37): C1474–C1484, 1995.
 85. Jobsis, F. F., and W. N. Stainsby. Oxidation of NADH during contractions of circulated skeletal muscle. Respir. Physiol. 4: 291–300, 1968.
 86. Katz, A. Mitochondrial redox state in skeletal muscle cannot be estimated with glutamate dehyrogenase system (letter). Am. J. Physiol. 254 (Cell Physiol. 23): C587–C590, 1988.
 87. Katz, A., and K. Sahlin. Regulation of lactic acid production during exercise. J. Appl. Physiol. 65: 509–518, 1988.
 88. Katz, A., and K. Sahlin. Effect of decreased oxygen availablity on NADH and lactate contents in human skeletal muscle during exercise. Acta Physiol. Scand. 131: 119–127, 1987.
 89. Katz, A., M. K. Spencer, and K. Sahlin. Failure of glutamate dehydrogenase system to predict oxygenation state of human skeletal muscle. Am. J. Physiol. 259 (Cell Physiol. 28): C26–C28, 1990.
 90. Kemp, G. J., D. J. Taylor, and G. K. Radda. Control of phosphocreatine synthesis during recovery from exercise in human skeletal muscle. NMR Biomed. 6: 66–72, 1993.
 91. Kemp, G. J., C. H. Thompson, A. L. Sanderson, and G. K. Radda. pH control in rat skeletal muscle during exercise, recovery from exercise, and acute respiratory acidosis. Magn. Reson. Med. 31: 103–109, 1994.
 92. Klug, G. A., and G. F. Tibbits. The effect of activity on calcium‐mediated events in striated muscle. Exerc. Sport Sci. Rev. 16: 1–60, 1988.
 93. Koretsky, A. P., and R. S. Balaban. Changes in pyridine nucleotide levels alter oxygen consumption and extramitochondrial phosphates in isolated mitochondria: a 31P NMR and NAD(P)H fluorescence study. Biochim. Biophys. Acta 893: 398–408, 1987.
 94. Kowalchuk, J. M., G. J. F. Heigenhauser, M. I. Lindinger, J. R. Sutton, and N. L. Jones. Factors influencing hydrogen ion concentration in muscle after intense exercise. J. Appl. Physiol. 65: 2080–2089, 1988.
 95. Kunz, W. S., A. V. Kuznetsov, W. Schulze, K. Eichorn, L. Schild, F. Stiggow, R. Bohnensack, S. Neuhof, H. Grasshoff, and H. W. Neumann. Functional characterization of mitochondrial oxidative phosphorylation in saponin‐skinned human muscle fibers. Biochim. Biophys. Acta 1144: 46–53, 1993.
 96. Kushmerick, M. J. Energetics of muscle contraction. In: Handbook of Physiology, Skeletal Muscle, Skeletal Muscle, edited by L. D. Peachey, R. H. Adrian, and S. R. Gieger. Bethesda, MD: Am. Physiol. Soc., 1983, p. 189–236, 1983.
 97. Kushmerick, M. J., and R. E. Davies. The chemical energetics of muscle contraction. II. The chemistry, efficiency, and power of maximally working sartorius muscles. Proc. R. Soc. Lond. B 174: 315–353, 1969.
 98. Kushmerick, M. J., and R. A. Meyer. Chemical changes in rat leg muscle by phosphorus nuclear magnetic resonance. Am. J. Physiol. 248 (Cell Physiol. 13): C542–C549, 1985.
 99. Kushmerick, M. J., R. A. Meyer, and T. R. Brown. Regulation of oxygen consumption in fast‐ and slow‐twitch muscle. Am. J. Physiol. 263 (Cell Physiol. 32): C598–C606, 1992.
 100. Kushmerick, M., T. S. Moerland, and R. W. Wiseman. Mammalian skeletal muscle fibers distinguished by contents of phosphocreatine, ATP, and Pi. Proc. Natl. Acad. Sci. U. S. A. 89: 7521–7525, 1992.
 101. La Noue, K. F., F. M. H. Jeffries, and G. K. Radda. Kinetic control of mitochondrial ATP systhesis. Biochemistry 25: 7667–7675, 1986.
 102. Lawson, J. W. R., and R. L. Veech. Effects of pH and free Mg2+ on the Keq of the creatine kinase reaction and other phosphate hydrolyses and phosphate transferases. J. Biol. Chem. 254: 6528–6537, 1979.
 103. Lawson, R., and J. Mowbray. Purine nucleotide metabolism: the discovery of a major new oligomeric adenosine tetraphosphate derivative in rat heart. Int. J. Biochem. 18: 407–412, 1986.
 104. Leberer, E., and D. Pette. Immunochemical quantification of sarcoplasmic reticulum Ca‐ATPase, of calsequestrin and of parvalbumin in rabbit skeletal muscles of defined fiber composition. Eur. J. Biochem. 156: 489–496, 1986.
 105. Lewis, S. F., and R. G. Haller. The pathophysiology of McArdle's disease: clues to regulation in exercise and fatigue. J. Appl. Physiol. 61: 391–401, 1986.
 106. Lowenstein, J. M. Ammonia production in muscle and other tissues: the purine nucleotide cycle. Physiol. Rev. 52: 382–414, 1972.
 107. Lowey, S., G. S. Waller, and K. M. Trybus. Function of skeletal muscle myosin heavy chain and light chain isoforms by an in vitro motility assay. J. Biol. Chem. 268: 20414–20418, 1993.
 108. Lowrey, O. H., D. W. Schulz, and J. V. Passonneau. Effects of adenylic acid on the kinetics of muscle phosphorylase a. J. Biol. Chem. 239: 1947–1953, 1964.
 109. Ma, J., M. Fill, C. M. Knudson, K. P. Campbell, and R. Coronado. Ryanodine receptor of skeletal muscle is a gap junction‐type channel. Science 242: 99–102, 1988.
 110. Mahler, M. First‐order kinetics of muscle oxygen consumption, and an equivalent proportionality between Qo2 and phosphorylcreatine level. J. Gen. Physiol. 86: 135–165, 1985.
 111. McAllister, R. M., R. W. Ogilvie, and R. L. Terjung. Impact of reduced cytochrome oxidase activity on peak oxygen consumption of muscle. J. Appl. Physiol. 69: 384–389, 1990.
 112. McAllister, R. M., and R. L. Terjung. Acute inhibition of respiratory capacity of muscle reduces peak oxygen consumption. Am. J. Physiol. 259 (Cell Physiol. 28): C889–C896, 1990.
 113. McCormack, J. G., A. P. Halestrap, and R. M. Denton. Role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physiol. Rev. 70: 391–425, 1990.
 114. McCully, K. K., S. Iotti, K. Kendrick, Z. Wang, J. D. Posner, J. Leigh, Jr., and B. Chance. Simultaneous in vivo measurements of HbO2 saturation and PCr kinetics after exercise in normal humans. J. Appl. Physiol. 77: 5–10, 1994.
 115. McMillin, J. B., and M. C. Madden. The role of calcium in the control of respiration by muscle mitochondria. Med. Sci. Sports Exerc. 21: 406–410, 1989.
 116. McMillin, J. B., and D. F. Pauly. Control of mitochondrial respiration in muscle. Mol. Cell. Biochem. 81: 121–129, 1988.
 117. Meyer, R. A. A linear model of muscle respiration explains monoexponential phosphocreatine changes. Am. J. Physiol. 254 (Cell Physiol. 23): C548–C553, 1988.
 118. Meyer, R. A. Linear dependence of muscle phosphocreatine kinetics on total creatine content. Am. J. Physiol. 257 (Cell Physiol. 26): C1149–C1157, 1989.
 119. Meyer, R. A., G. R. Adams, M. J. Fisher, P. F. Dillon, J. M. Krisanda, T. R. Brown, and M. J. Kushmerick. Effect of decreased pH on force and phosphocreatine in mammalian skeletal muscle. Can. J. Physiol. Pharmacol. 69: 305–310, 1991.
 120. Meyer, R. A., T. R. Brown, B. L. Krilowicz, and M. J. Kushmerick. Phosphagen and intracellular pH changes during contraction of reatine depleted rat muscle. Am. J. Physiol. 250 (Cell Physiol. 19): C264–C274, 1986.
 121. Meyer, R. A., T. R. Brown, and M. J. Kushmerick. Phosphorus nuclear magnetic resonance of fast‐ and slow‐twitch muscle. Am. J. Physiol. 248 (Cell Physiol. 17): C279–C287, 1985.
 122. Meyer, R. A., M. J. Fisher, S. J. Nelson, and T. R. Brown. Evaluation of manual methods for integration of in vivo phosphorus NMR spectra. NMR Biomed. 1: 131–135, 1988.
 123. Meyer, R. A., M. J. Kushmerick, and T. R. Brown. Application of 31P‐NMR spectroscopy to the study of striated muscle metabolism. Am. J. Physiol. 242 (Cell Physiol. 11): C1–C11, 1982.
 124. Meyer, R. A., and R. L. Terjung. Differences in ammonia and adenylate metabolism in contracting fast‐ and slow‐twitch muscle. Am. J. Physiol. 237 (Cell Physiol. 6): C111–C118, 1979.
 125. Meyer, R. A., H. L. Sweeney, and M. J. Kushmerick. A simple analysis of the “phosphocreatine shuttle”. Am. J. Physiol. 246 (Cell Physiol. 15): C365–C377, 1984.
 126. Meyer, R. A., and R. L. Terjung. AMP deamination and IMP resamination in working skeletal muscle. Am. J. Physiol. 239 (Cell Physiol. 8): C32–C38, 1980.
 127. Moerland, T. S., N. G. Wolf, and M. J. Kushmerick. Administration of a creatine analogue induces isomyosin transitions in muscle. Am. J. Physiol. 257 (Cell Physiol. 26): C810–C816, 1989.
 128. Moon, R. B., and J. H. Richards. Determination of intracellular pH by 31P magnetic resonance. J. Biol. Chem. 248: 7276–7278, 1973.
 129. Morgan, H. E., and A. Parmeggiani. Regulation of glycogenolysis in muscle HI: control of muscle glycogen phosphorylase activity. J. Biol. Chem. 239: 2440–2445, 1964.
 130. Morrison, J. F., and W. W. Cleland. Isotope exchange studies of the mechanism of the reaction catalyzed by adenosine triphosphate: creatine phosphotransferase. J. Biol. Chem. 241: 673–683, 1966.
 131. Needham, D. M. Machina Carnis: The Biochemistry of Muscular Contraction and its Historical Development. Cambridge: Cambridge University Press, 1971.
 132. Nioka, S., Z. Argov, G. P. Dobson, R. E. Forster, H. V. Subramanian, R. L. Veech, and B. Chance. Substrate regulation of mitochondrial oxidative phosphorylation in hypercapnic rabbit muscle. J. Appl. Physiol. 72: 521–528, 1992.
 133. Paddle, B. M. A cytoplasmic component of pyridine nucleotide flouresence in rat diaphragm: evidence from comparisons with flavoprotein flourescence. Pflugers Arch. 404: 326–331, 1985.
 134. Parkhouse, W. S. Regulation of skeletal muscle metabolism by enzyme binding. Can. J. Physiol. Pharmacol. 70: 150–156, 1992.
 135. Peachey, L. D. Excitation‐contraction coupling: the link between the surface and the interior of a muscle cell. J. Exp. Biol. 115: 91–98, 1985.
 136. Pessah, I. N., R. A. Stambuk, and J. E. Casida. Ca2+‐activated ryanodine binding: mechanisms of sensitivity and intensity modulation by Mg2+, caffeine, and adenine nucleotides. Mol. Pharmacol. 31: 232–238, 1987.
 137. Pette, D., and R. S. Staron. Cellular and molecular diversities of mammalian skeletal muscle fibers. Rev. Physiol. Biochem. Pharmacol. 116: 1–76, 1990.
 138. Rall, J. A. Energetic aspects of skeletal muscle contraction: implication of fiber types. Exerc. Sport Sci. Rev. 13: 33–74, 1985.
 139. Rall, J. A. Sense and nonsense about the Fenn effect. Am. J. Physiol. 242 (Heart Circ. Physiol. 11): H1–H6, 1982.
 140. Rall, J. A. Energetics of Ca2+ cycling during skeletal muscle contraction. Federation Proc. 41: 155–160, 1982.
 141. Ren, J. M., and E. Hultman. Regulation of glycogenolysis in human skeletal muscle. J. Appl. Physiol. 67: 2243–2248, 1989.
 142. Ren, J. M., B. A. Marshall, E. A. Gulve, J. Gao, D. W. Johnson, J. O. Holloszy, and M. Mueckler. Evidence from transgenic mice that glucose transport is rate‐limiting for glycogen deposition and glycolysis in skeletal muscle. J. Biol. Chem. 268: 16113–16115, 1993.
 143. Rios, E., and G. Pizarro. Voltage sensor of excitation‐contraction coupling in skeletal muscle. Physiol. Rev. 71: 849–908, 1991.
 144. Roos, A., and W. F. Boron. Intracellular pH. Physiol. Rev. 61: 296–434, 1981.
 145. Rossi, A. M., H. M. Eppenberger, P. Volpe, R. Cutrofo, and T. Wallimann. Muscle‐type MM creatine kinase is specifically bound to sarcoplasmic reticulum and can support Ca2+ uptake and regulate local ATP/ADP ratios. J. Biol. Chem. 265: 5258–5266, 1990.
 146. Rossini, L., P. Rossini, and B. Chance. Continuous readout of cytochrome b, flavin and pyridine nucleotide oxido‐reduction processes in the perfused frog heart and contracting skeletal muscle. Pharm. Res. 22: 349–365, 1991.
 147. Roth, D. A., and G. A. Brooks. Lactate transport is mediated by a membrane‐bound carrier in rat skeletal muscle sarcolemmal vesicles. Arch. Biochem. Biophys. 944: 213–222, 1988.
 148. Rottenberg, H. The thermodynamic description of enzyme‐catalyzed reactions. Biophys. J. 13: 503–511, 1973.
 149. Rouslin, W. The mitochondrial adenosine 5′‐triphosphatase in slow and fast rate hearts. Am. J. Physiol. 252 (Heart Circ. Physiol. 21): H622–H637, 1987.
 150. Rowell, L. B. Muscle blood flow in humans: how high can it go? Med. Sci. Sports Exerc. 20: S97–S103, 1988.
 151. Rundell, K. W., P. C. Tullson, and R. L. Terjung. AMP deaminase binding in contracting rat skeletal muscle. Am. J. Physiol. 263 (Cell Physiol. 32): C287–C293, 1992.
 152. Rundell, K. W., P. C. Tullson, and R. L. Terjung. Altered kinetics of AMP deaminase by myosin binding. Am. J. Physiol. 263 (Cell Physiol. 32): C294–C299, 1992.
 153. Sabbadini, R. A., and A. S. Dahms. Biochemical properties of isolated transverse tubular membranes. J. Bioenerg. Biomembr. 21: 163–213, 1989.
 154. Sahlin, K. Intracellular pH and energy metabolism in skeletal muscle of man. Acta Physiol. Scand. 455: 1–56, 1978.
 155. Sahlin, K. Control of energetic processes in contracting human skeletal muscle. Biochem. Soc. Trans. 19: 353–358, 1991.
 156. Sahlin, K. NADH and NADPH in human skeletal muscle at rest and during ischaemia. Clin. Physiol. 3: 477–485, 1983.
 157. Sahlin, K., J. Gorski, and L. Edstrom. Influence of ATP turnover and metabolite changes on IMP formation and glycolysis in rat skeletal muscle. Am. J. Physiol. 259 (Cell Physiol. 28): C409–C412, 1990.
 158. Sahlin, K., R. C. Harris, and E. Hultman. Creatine kinase equilibrium and lactate content compared with muscle pH in tissue samples obtained after isometric exercise. Biochem. J. 152: 173–180, 1975.
 159. Sahlin, K., R. C. Harris, and E. Hultman. Resynthesis of creatine phosphate in human muscle after exercise in relation to intramuscular pH and availability of oxygen. Scand. J. Clin. Lab. Invest. 39: 551–558, 1979.
 160. Sahlin, K., R. C. Harris, B. Nylind, and E. Hultman. Lactate content and pH in muscle samples obtained after dynamic exercise. Pflugers Arch. 367: 143–149, 1976.
 161. Sahlin, K., A. Katz, and J. Henriksson. Redox state and lactate accumulation in human skeletal muscle during dynamic exercise. Biochem. J. 245: 551–556, 1987.
 162. Sapega, A. A., D. P. Sokolow, T. J. Graham, and B. Chance. Phosphorus nuclear magnetic resonance: a non‐invasive technique for the study of muscle bioenergetics during exercise. Med. Sci. Sports Exerc. 19: 410–420, 1987.
 163. Segel, I. H. Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady‐State Enzyme Systems. New York: John Wiley & Sons, 1975.
 164. Shoubridge, E. A., R. A. J. Challiss, D. J. Hayes, and G. K. Radda. Biochemical adaptation in the skeletal muscle of rats depleted of creatine with the substrate analogue β‐guanidinopropionic acid. Biochem. J. 232: 125–131, 1985.
 165. Shoubridge, E. A., and G. K. Radda. A gated 31P‐NMR study of tetanic contraction in rat muscle depleted of phosphocreatine. Am. J. Physiol. 252 (Cell Physiol. 21): C532–C542, 1987.
 166. Smith, I. C. H. Energetics of activation in frog and toad muscle. J. Physiol. (Lond.) 220: 583–599, 1972.
 167. Smith, J. S., R. Coronado, and G. Meissner. Sarcoplasmic reticulum contains adenine nucleotide‐activated calcium channels. Nature 316: 446–449, 1985.
 168. Soderlund, K., and E. Hultman. ATP and phosphocreatine changes in single human muscle fibers after intense electrical stimulation. Am. J. Physiol. 261 (Endocrinol. Metab. 25): E737–E741, 1991.
 169. Spriet, L. L. Anaerobic metabolism in human skeletal muscle during short‐term, intense activity. Can. J. Physiol. Pharmacol. 70: 157–165, 1992.
 170. Spriet, L. L., K. Soderlund, and E. Hultman. Energy cost and metabolic regulation during intermittent and continuous tetanic contractions in human skeletal muscle. Can. J. Physiol. Pharmacol. 66: 134–139, 1988.
 171. Srere, P. A. Complexes of sequential metabolic enzymes. Ann. Rev. Biochem. 56: 89–124, 1987.
 172. Stanley, W. C., and R. J. Connett. Regulation of muscle carbohydrate metabolism during exercise. FASEB J. 5: 2155–2159, 1991.
 173. Stewart, P. A. Modern quantitative acid‐base chemistry. Can. J. Physiol. Pharmacol. 61: 1444–1461, 1983.
 174. Stoner, C. D. An investigation of the relationships between rate and driving force in simple uncatalyzed and enzyme‐catalyzed reactions with appplications of the findings to chemiosmotic reactions. Biochem. J. 283: 541–552, 1992.
 175. Sweeney, H. L. The importance of the creatine kinase reaction: the concept of metabolic capacitance. Med. Sci. Sports Exerc. 26: 30–36, 1994.
 176. Sweeney, H. L., B. Bowman, and J. T. Stull. Myosin light chain phosphorylation in vertebrate striated muscle: regulation and function. Am. J. Physiol. 264 (Cell Physiol. 33): C1085–C1095, 1993.
 177. Sweeney, H. L., M. J. Kushmerick, K. Mabuchi, F. A. Streter, and J. Gergely. Myosin alkali light chain and heavy chain variations correlate with altered shortening velocity of isolated skeletal muscle muscle fibers. J. Biol. Chem. 263: 9034–9039, 1988.
 178. Tamura, M., O. Hazeki, S. Nioka, and B. Chance. In vivo study of tissue oxygen metabolism using optical and nuclear magnetic resonance spectroscopies. Ann. Rev. Physiol. 51: 813–834, 1989.
 179. Tate, C. A., and G. E. Taffet. The regulatory role of calcium in striated muscle. Med. Sci. Sports Exerc. 21: 393–398, 1989.
 180. Teodosiu, D. C., G. Cederblad, and E. Hultman. PDC activity and acetyl group accumulation in skeletal muscle during isometric contraction. J. Appl. Physiol. 74: 1712–1718, 1993.
 181. Trevida, B., and W. H. Danforth. Effect of pH on the kinetics of frog muscle phosphofructokinase. J. Biol. Chem. 241: 4110–4114, 1966.
 182. Tsika, R. W. Transgenic animal models. Exerc. Sport Sci. Rev. 22: 361–388, 1994.
 183. Tullson, P. C., D. M. Whitlock, and R. L. Terjung. Adenine nucleotide degradation in slow‐twitch red muscle. Am. J. Physiol. 258 (Cell Physiol. 27): C258–C265, 1990.
 184. Ugurbil, K., P. B. Kingsley‐Hickman, E. Y. Sako, S. Zimmer, P. Mohanakrishnan, P. M. L. Robitaille, W. J. Thoma, A. Johnson, J. E. Foker, and A. H. L. From. 31P NMR studies of the kinetics and regulation of oxidative phosphorylation in the intact myocardium. Ann. N. Y. Acad. Sci. 508: 265–286, 1987.
 185. Van der Meer, R., H. V. Westerhoff, and K. van Dam. Linear relation between rate and thermodynamic force in enzyme‐catalyzed reactions. Biochim. Biophys. Acta 591: 488–493, 1980.
 186. Van Deursen, J., A. Heerschap, F. Oerlemans, W. Rutten‐beek, P. Jap, H. ter Leak, and B. Wieringa. Skeletal muscles of mice deficient in muscle creatine kinase lack burst activity. Cell 74: 621–631, 1993.
 187. Veech, R. L., J. W. R. Lawson, N. W. Cornell, and H. A. Krebs. Cytosolic phosphorylation potential. J. Biol. Chem. 254: 6538–6547, 1979.
 188. Wallimann, T., and H. M. Eppenberger. The subcellular compartmentation of creatine kinase isozymes as a precondition for a proposed phosphoryl‐creatine circuit. Prog. Clin. Biol. Res. 344: 877–889, 1990.
 189. Wallimann, T., and H. M. Eppenberger. Localization and function of M‐line‐bound creatine kinase: M‐band model and creatine phosphate shuttle. Cell Muscle Motil. 6: 239–285, 1985.
 190. Wallimann, T. T. Schlosser, and H. M. Eppenberger. Function of M‐line‐bound creatine kinase as intramyofibrillar ATP regenerator at the receiving end of the phosphoryl‐creatine shuttle in muscle. J. Biol. Chem. 259: 5238–5246, 1984.
 191. Weibel, E. R. The Pathway for Oxygen. Cambridge, MA: Harvard University Press, 1984.
 192. Wendt, I. R., and J. B. Chapman. Flourometric studies of recovery metabolism of rat fast‐ and slow‐twitch muscles. Am. J. Physiol. 230: 1644–1649, 1976.
 193. Wendt, I. R., and C. L. Gibbs. Energy production of rat extensor digitorum longus muscle. Am. J. Physiol. 224: 1081–1086, 1973.
 194. Westerblad, H., J. A. Lee, J. Lannergren, and D. G. Allen. Cellular mechanisms of fatigue in skeletal muscle. Am. J. Physiol. 261 (Cell Physiol. 30): C195–C209, 1991.
 195. Westerhoff, H. V, and K. van Dam. Thermodynamics and Control of Biological Free‐Energy Transduction. Amsterdam: Elsevier, 1987.
 196. Whalen, R. G. Myosin isozymes as molecular markers for muscle physiology. J. Exp. Biol. 115: 43–53, 1985.
 197. Wheeler, T. J., and J. M. Lowenstein. Adenylate deaminase from rat muscle. Regulation by purine nucleotides and orthophosphate in the presense of 150mM KCl. J. Biol. Chem. 254: 8994–8999, 1979.
 198. Whitlock, D. M., and R. L. Terjung. ATP depletion in slow‐twitch red muscle of rat. Am. J. Physiol. 253 (Cell Physiol. 22): C426–C432, 1987.
 199. Wilson, D. F. Factors affecting the rate and energetics of mitochondrial oxidative phosphorylation. Med. Sci. Sports Exerc. 26: 37–43, 1994.
 200. Woledge, R. C., N. A. Curtin, and E. Homsher. Energetic aspects of muscle contraction. Monogr. Physiol. Soc., Vol. 41, London: Academic Press, 1985.
 201. Wolfe, B. R., T. E. Graham, and J. K. Barclay. Hyperoxia, mitochondrial redox state, and lactate metabolism of in situ canine muscle. Am. J. Physiol. 253 (Cell Physiol. 22): C263–C268, 1987.
 202. Wu, K. D., and J. Lytton. Molecular cloning and quantification of sarcoplasmic reticulum Ca2+‐ATPase isoforms in rat muscles. Am. J. Physiol. 264 (Cell Physiol. 33): C333–C341, 1993.
 203. Zamanyi, I., and I. N. Pessah. Comparison of [3H]ryanodine receptors and Ca++ release from rat cardiac and rabbit skeletal muscle sarcoplasmic reticulum. J. Pharmacol. Exp. Ther. 256: 938–946, 1991.

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Ronald A. Meyer, Jeanne M. Foley. Cellular Processes Integrating the Metabolic Response to Exercise. Compr Physiol 2011, Supplement 29: Handbook of Physiology, Exercise: Regulation and Integration of Multiple Systems: 841-869. First published in print 1996. doi: 10.1002/cphy.cp120118