Control of Respiration in Intact Muscle

  • Michael Mahler
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 194)


We believe that the hydrolysis of ATP provides the free energy for all cell function, and we know that the ultimate source of almost all ATP produced in muscle is oxidative metabolism (Fig. 1). We’d like to know, in as much detail as possible, the mechanism coupling these two fundamental processes, whereby a change in the rate of ATP utilization leads to a change in the rate of oxidative phosphorylation. That brings me to my second reason for choosing the first figure. In what can be thought of as perhaps the first attempt to model the control of respiration in muscle, Chance and Connelly’ used a scheme little more complicated than this. Having determined the responses of isolated mitochondria to limiting concentrations of ADP or inorganic phosphate (Pi), they assumed that the rest of the cell could be represented simply as an ATPase. I mention this not to impugn or embarass two distinguished scientists, but to illustrate the point that, in general, workers in this field have shown a surprising lack of awareness of, or concern for, events occurring outside the mitochondrial inner membrane. To the extent that this audience shares that attitude, I hope to correct it. Fig. 2 shows a current, schematic description of the reactions believed to couple oxidative phosphorylation to ATP hydrolysis, which I hope will meet with everyone’s approval.


Creatine Kinase Oxidative Phosphorylation Oxidative Metabolism Order Kinetic Frog Skeletal Muscle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    B. Chance and C. M. Connelly, A method for the estimation of the increase in concentration of adenosine diphosphate in muscle sarcosomes following a contraction, Nature (London) 179: 1235 (1957).CrossRefGoogle Scholar
  2. 2.
    E. J. Davis and L. Lumeng, Relationships between the phosphorylation potentials generated by liver mitochondria and respiratory state under conditions of adenosine diphosphate control, J. Biol. Chem. 250: 2275 (1975).Google Scholar
  3. 3.
    K. Nishiki, M. Erecinska, and D. F. Wilson, Energy relationships between cytosolic metabolism and mitochondrial respiration in rat heart, Am. J. Physiol. 234: C73 (1978).PubMedGoogle Scholar
  4. 4.
    J. H. Williamson, Mitochondrial function in the heart, Ann. Rev. Physiol. 41: 485 (1979).CrossRefGoogle Scholar
  5. 5.
    R. G. Hansford, Control of mitochondrial respiration, Curr. Top. Bioenerg. 10: 217 (1980).Google Scholar
  6. 6.
    W. E. Jacobus, R. W. Moreadith, and K. M. Vandegaer, Mitochondrial respiratory control. Evidence against the regulation of respiration by extramitochondrial phosphorylation potentials or by [ATP]/[ADP] ratios, J. Biol. Chem. 257: 2397 (1982).PubMedGoogle Scholar
  7. 7.
    A. K. Groen, R. Van der Meer, H. V. Westerhoff, R. J. A. Wanders, T. P. M. Akerboom, and J. M. Tager, Control of metabolic fluxes, in: “Metabolic Compartmentation”, H. Sies, ed., Academic Press, New York (1982).Google Scholar
  8. 8.
    M. Mahler, The relationship between initial creatine phosphate breakdown and recovery oxygen consumption for a single isometric tetanus of the frog sartorius muscle at 20°C, J. Gen. Physiol. 73: 159 (1979).PubMedCrossRefGoogle Scholar
  9. 9.
    M. Mahler, C. Louy, and E. Homsher, A reappraisal of diffusion, solubility, and consumption of oxygen in frog skeletal muscle, J. Gen. Physiol. (submitted).Google Scholar
  10. 10.
    M. Mahler, Diffusion and consumption of oxygen in the resting frog sartorius muscle, J. Gen. Physiol. 71: 533 (1978).PubMedCrossRefGoogle Scholar
  11. 11.
    M. Mahler, Kinetics of oxygen consumption after a single isometric tetanus of the frog sartorius muscle at 20°C, J. Gen. Physiol. 71: 559 (1978).PubMedCrossRefGoogle Scholar
  12. 12.
    D. K. Hill, The time course of the oxygen consumption of stimulated frog’s muscle, J. Physiol. (London) 98: 207 (1940).Google Scholar
  13. 13.
    D. K. Hill, The time course of evolution of oxidative recovery heat of frog’s muscle, J. Physiol. (London) 98: 454 (1940).Google Scholar
  14. 14.
    F. D. Carlson, The mechanochemistry of muscular contraction, a critical review of in vivo studies, Prog. Biophys. 13: 262 (1962).Google Scholar
  15. 15.
    W. F. H. Mommaerts, Energetics of muscular contraction, Physiol. Rev. 49: 427 (1969).Google Scholar
  16. 16.
    C. Gilbert, K. M. Kretzschmar, D. R. Wilkie, and R. C. Woledge, Chemical change and energy output during muscular contraction, J. Physiol. (London) 218: 163 (1971).Google Scholar
  17. 17.
    E. Homsher, J. A. Rall, A. Wallner, and N. V. Ricciutti, Energy liberation and chemical change in frog skeletal muscle during single isometric contraction, J. Gen. Physiol. 65: 1 (1975).PubMedCrossRefGoogle Scholar
  18. 18.
    M. J. Dawson, D. G. Gadian, and D. R. Wilkie, Contraction and recovery of living muscles studied by 31P nuclear magnetic resonance, J. Physiol. (London) 267: 703 (1977).Google Scholar
  19. 19.
    P. Arese, R. Kirsten, and E. Kirsten, Metabolitgehalte und -gleichgewichte nach tetanischer Kontraktion des Taubebrustmuskels und des Rattenskeletmuskels, Biochem. Z. 341: 523 (1965).Google Scholar
  20. 20.
    R. H. T. Edwards, R. C. Harris, E. Hultman, and L. Nordesjo, Phosphagen utilization and resynthesis in successive isometric contractions, sustained to fatigue, of the quadriceps muscle in man, J. Physiol. (London) 224: 40P (1972).Google Scholar
  21. 21.
    D. C. Gower and K. M. Kretzschmar, Heat production and chemical change during isometric contraction of rat soleus muscle, J. Physiol. (London) 258: 659 (1976).Google Scholar
  22. 22.
    M. T. Crow and M. J. Kushmerick. Chemical energetics of slow and fast-twitch muscles of the mouse, J. Gen. Physiol. 79: 147 (1982).CrossRefGoogle Scholar
  23. 23.
    J. Piiper and P. Spiller, Repayment of 02 debt and resynthesis of high-energy phosphates in gastrocnemius muscle of the dog, J. Appl. Physiol. 28: 657 (1970).PubMedGoogle Scholar
  24. 24.
    M. J. Kushmerick and R. J. Paul, Aerobic recovery metabolism following a single isometric tetanus in frog sartorius muscle at 0°C, J. Physiol. (London) 254: 693 (1976).Google Scholar
  25. 25.
    F. D. Carlson, D. Hardy, and D. R. Wilkie, The relation between heat produced and phosphorylcreatine split during isometric contraction of frog’s muscle, J. Physiol. (London) 189: 209 (1967).Google Scholar
  26. 26.
    H. J. Hohorst, M. Reim, and H. Bartels, Studies on the creatine kinase equilibrium in muscle and the significance of ATP and ADP levels, Biochem. Biophys. Res. Commun. 7: 142 (1962).CrossRefGoogle Scholar
  27. 27.
    J. Piiper, P. E. DiPrampero, and P. Cerretelli, Oxygen debt and high energy phosphates in gastrocnemius muscle of the dog, Am. J. Physiol. 215: 523 (1968).PubMedGoogle Scholar
  28. 28.
    M. J. Kushmerick, unpublished results.Google Scholar
  29. 29.
    W. E. Jacobus and D. M. Diffley, Regulation of heart mitochondrial respiration by [creatine] and [phosphocreatine], Biophys. J. 41: 249a (1983).Google Scholar
  30. 30.
    W. E. Jacobus, Regulation of mitochondrial respiration, (these proceedings).Google Scholar
  31. 31.
    D. F. Wilson, M. Erecinska, and P. L. Dutton, Thermodynamic relationships in mitochondrial oxidative phosphorylation, Annu. Rev. Biophys. Bioeng. 3: 203 (1974).PubMedCrossRefGoogle Scholar
  32. 32.
    B. Chance, G. Mauriello, and X. Aubert, ADP arrival at muscle mitochondria following a twitch, in: “Muscle as a Tissue”, K. Rodahl and S. M. Horvath, eds., McGraw-Hill, New York (1962).Google Scholar
  33. 33.
    P. Mitchell, Chemiosmotic coupling in oxidative and photosynthetic phosphorylation, Biol. Rev. Cambridge Phil. Soc. 41: 445 (1966).CrossRefGoogle Scholar
  34. 34.
    P. Mitchell, Vectorial chemistry and the molecular mechanics of chemiosmotic coupling: power transmission by proticity, Biochem. Soc. Trans. 4: 399 (1976).Google Scholar
  35. 35.
    P. V. Vignais, Molecular and physiological aspects of adenine nucleotide transport in mitochondria, Biochim. Biophys. Acta 456: 1 (1976).Google Scholar
  36. 36.
    M. Klingenberg, The ADP-ATP translocation in mitochondria, a membrane potential controlled transport, J. Membr. Biol. 56: 97 (1980).PubMedCrossRefGoogle Scholar
  37. 37.
    J. M. H. Souverijn, L. A. Huisman, J. Rosing, and A. Kemp, Jr., Comparison of ADP and ATP as substates for the adenine nucleotide translocator, Biochim. Biophys. Acta 305: 185 (1973).CrossRefGoogle Scholar
  38. 38.
    H. Jacobs, H. W. Heldt, and M. Klingenberg, High activity of creatine kinase in mitochondria from heart and brain and evidence for a separate mitochondrial isoenzyme of creatine kinase, Biochem. Biophys. Res. Commun. 16: 516 (1964).CrossRefGoogle Scholar
  39. 39.
    J. A. Illingworth, W. C. L. Ford, K. Kobayashi, and J. R. Williamson, Regulation of myocardial energy metabolism, Recent Adv. Stud. Card. Struct. Metab. 8: 271 (1975).Google Scholar
  40. 40.
    J. W. R. Lawson and R. L. Veech, Effects of pH and free Mg2+ on the Keg of the creatine kinase reaction and other phosphate hydrolyses and phosphate transfer reactions, J. Biol. Chem. 254: 6528 (1979).PubMedGoogle Scholar
  41. 41.
    R. A. Meyer, Am. J. Physiol. (in press).Google Scholar
  42. 42.
    V. A. Saks, N. V. Lipina, V. N. Smirnov, and E. I. Chazov, Studies of energy transport in heart cells. The functional coupling between mitochondrial creatine phosphokinase and ATP-ADP translocase: kinetic evidence, Arch. Biochem. Biophys. 173: 34 (1976).CrossRefGoogle Scholar
  43. 43.
    V. A. Saks, V. V. Kupriyanov, G. V. Elizarova, and W. E. Jacobus, Studies of energy transport in heart cells. The importance of creatine kinase localization for the coupling of mitochondrial phosphorylcreatine production to oxidative phosphorylation, J. Biol. Chem. 255: 755 (1980).PubMedGoogle Scholar
  44. 44.
    R. W. Moreadith and W. E. Jacobus, Creatine kinase of heart mitochondria. Functional coupling of ADP transfer to the adenine nucleotide translocase, J. Biol. Chem. 257: 899 (1982).PubMedGoogle Scholar
  45. 45.
    S. Erickson-Viitanen, P. Viitanen, P. J. Geiger, W. C. T. Yang, and S. P. Bessman, Compartmentation of mitochondrial creatine phosphokinase. I. Direct demonstration of compartmentation with the use of labeled precurcors, J. Biol. Chem. 257: 14395 (1982).Google Scholar
  46. 46.
    S. Erickson-Viitanen, P. J. Geiger, P. Viitanen, and S. P. Bess-man, Compartmentation of mitochondrial creatine phosphokinase. II. The importance of the outer mitochondrial membrane for mitochondrial compartmentation, J. Biol. Chem. 257: 14405 (1982).PubMedGoogle Scholar
  47. 47.
    E. Pfaff, H. W. Heldt, and M. Klingenberg, Adenine translocation of mitochondria. Kinetics of the adenine nucleotide exchange, Eur. J. Biochem. 10: 484 (1969).PubMedCrossRefGoogle Scholar
  48. 48.
    I. H. Segel, “Biochemical Calculations”, Wiley, New York (1967), p. 245.Google Scholar
  49. 49.
    B. Chance and G. R. Williams, Respiratory enzymes in oxidative phosphorylation. VI. The effects of adenosine diphosphate on azide-treated mitochondria, J. Biol. Chem. 221: 477 (1956).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Michael Mahler
    • 1
  1. 1.Department of Kinesiology and Jerry Lewis NeuromuscularResearch Center, UCLALos AngelesUSA

Personalised recommendations