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Is it possible to predict any properties of oxidative phosphorylation in a theoretical way?

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Abstract

Two theoretical approaches applied to oxidative phosphorylation, namely Metabolic Control Analysis (MCA) [1-7] and Non-Equilibrium Thermodynamics (NET) [8-11], turned out to be very useful tools for quantitative description and understanding of control and regulation of this process. However, they were not able to predict any new properties of the considered system. On the other hand, the previously developed dynamic model of oxidative phosphorylation [12-17], representing a kinetic approach, allowed to formulate several interesting predictions which can be tested experimentally. The most important of these predictions are: (1) Different steps of ATP-production must be directly activated to a similar extent as ATP-consumption during stimulation of ATP turnover by calcium-acting hormones as well as by neural signals during muscle contraction; (2) A universal activator/regulatory mechanism responsible for such a precise balance of activation should be identified; (3) The flux-force relationship for cytochrome oxidase can be inverse during the transition towards hypoxia and anoxia, when oxygen concentration falls below 30 μM; (4) The flux-force relationship can depend on the way in which the thermodynamic force is changed; (5) The pattern of metabolic control is completely different in normoxic and hypoxic conditions; in the latter case cytochrome oxidase has the flux control coefficient close to unity. Thus, the kinetic model of oxidative phosphorylation seems to be a useful scientific tool, offering some novel theoretical predictions, which then can be tested in the experimental way.

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References

  1. Kacser H, Burns JA: The control of flux. Symp Sos Exp Biol 32: 61–104, 1973

    Google Scholar 

  2. Heinrich R, Rapoport TA: A linear steady-state treatment of enzymatic chains. General properties, control and strength. Eur J Biochem 42: 89–95, 1974

    Google Scholar 

  3. Groen AK, Wanders RJA, Westerhoff HV, van der Meer R, Tager JM: Quantification of the contribution of various steps to the control of mitochondrial respiration. J Biol Chem 257: 2754–2757, 1982

    Google Scholar 

  4. Lettelier T, Malgat M, Mazat J-P: Control of oxidative phosphorylation in rat muscle mitochondria: Implications for mitochondrial myopathies. Biochim Biophys Acta 1141: 58–64, 1993

    Google Scholar 

  5. Jouaville L, Ichas F, Lettelier T, Mazat J-P: Control of ATP flux in rat muscle mitochondria. In: S Schuster, M Rigoulet, R Ouabi, J-P Mazat (eds). Modern Trends in BioThermoKinetics. Plenum Press, New York, 1993, pp 319–325

    Google Scholar 

  6. Fell DA: Metabolic Control Analysis: A survey of its theoretical and experimental development. Biochem J 286: 313–330, 1992

    Google Scholar 

  7. Brown GC: Control of respiration and ATP synthesis in mammalian mitochondria and cells. Biochem J 284: 1–13, 1992

    Google Scholar 

  8. Rottenberg H: The thermodynamic description of enzyme-catalyzed reactions. Biophys J 13: 503–511, 1973

    Google Scholar 

  9. Rottenberg H: Non-equilibrium thermodynamics of energy conversion in bioenergetics. Biochim Biophys Acta 549: 225–253, 1979

    Google Scholar 

  10. Westerhoff HV, van Dam K: Thermodynamics and control of free-energy transduction, Elsevier, Amsterdam, 1987

    Google Scholar 

  11. Stucki JW: The optimal efficiency and the economic degrees of coupling of oxidative phosphorylation. Eur J Biochem 109: 269–283, 1980

    Google Scholar 

  12. Korzeniewski B, Froncisz W: An extended dynamic model of oxidative phosphorylation. Biochim Biophys Acta 1060: 210–223, 1991

    Google Scholar 

  13. Korzeniewski B, Froncisz W: Theoretical studies on the control of the oxidative phosphorylation system. Biochim Biophys Acta 1102: 67–75, 1992

    Google Scholar 

  14. Korzeniewski B: Simulation of oxidative phosphorylation in hepatocytes. Biophys Chem 58: 215–224, 1996

    Google Scholar 

  15. Korzeniewski B: Simulation of state 4 → state 3 transition in isolated mitochondria. Biophys Chem 57: 143–153, 1996

    Google Scholar 

  16. Korzeniewski B: Regulation of cytochrome oxidase: Theoretical studies. Biophys Chem 59: 75–86, 1996

    Google Scholar 

  17. Korzeniewski B, Mazat J-P: Theoretical studies on the control of oxidative phosphorylation in muscle mitochondria: Application to mitochondrial deficiencies. Biochem J 319: 143–148, 1996

    Google Scholar 

  18. Mitchell P: Coupling of phosphorylation to electron and hydrogen transfer by a chemiosmotic-type of mechanism. Nature 191:144–148, 1961

    Google Scholar 

  19. Chance B, Williams GR: Respiration enzymes in oxidative phosphorylation. l. Kinetics of oxygen utilization. J Biol Chem 217: 383–393, 1955

    Google Scholar 

  20. Chance B, Williams GR: The respiratory chain and oxidative phosphorylation. Adv Enzymol 17: 65–134, 1956

    Google Scholar 

  21. Nicholls DG: The influence of respiration and ATP hydrolysis on the proton-electrochemical gradient across the inner membrane of rat-liver mitochondria as determined by ion distribution. Eur J Biochem 50: 305–315, 1974

    Google Scholar 

  22. Duszyäski J, Bogucka K, Wojtczak L: Homeostasis of the protonmotive force in phosphorylating mitochondria. Biochim Biophys Acta 767: 540–547, 1984

    Google Scholar 

  23. Bohnensack R, Gellerich FN, Schild L, Kunz W: The function of the adenine nucleotide translocator. Biochim Biophys Acta 1018: 182–184, 1990

    Google Scholar 

  24. Smith CM, Bryla J, Williamson JR: Regulation of mitochondrial α-ketoglutarate metabolism by product inhibition at α-ketoglutarate dehydrogenase. J Biol Chem 249: 1497–1505, 1974

    Google Scholar 

  25. Wilson DF, Ereciriska M, Drown C, Silver IA: The oxygen dependence of cellular energy metabolism. Arch Biochem Biophys 195: 485–493, 1979

    Google Scholar 

  26. Kashiwagura T, Wilson DF, Ereciäska M: Oxygen dependence of cellular metabolism: the effect of O2 tension on gluconeogenesis and urea synthesis in isolated rat hepatocytes. J Cell Physiol 120: 13–18, 1984

    Google Scholar 

  27. Gnaiger E, Steinlechner-Maran R, Mendez G, Eberl T, Margerite R: Control of mitochondrial and cellular respiration by oxygen. J Bioenerg Biomembr 27: 583–596, 1995

    Google Scholar 

  28. Wanders RJA, Westerhoff HV: Sigmoidal relation between mitochondrial respiration and log([ATP]/[ADP])out under conditions of extramitochondrial ATP utilization. Implications for the control and thermodynamics of oxidative phosphorylation. Biochemistry 27: 7832–7840, 1988

    Google Scholar 

  29. Hafner RP, Brown GC, Brand MD: Analysis of the control of respiration rate, phosphorylation rate, proton leak rate and protonmotive force in isolated mitochondria using the ‘top-down’ approach of metabolic control theory. Eur J Biochem 188: 313–319, 1990

    Google Scholar 

  30. Brown GC, Lakin-Thomas PL, Brand MD: Control of respiration and oxidative phosphorylation in isolated rat liver cells. Eur J Biochem 192: 355–362, 1990

    Google Scholar 

  31. Small JR, Kacser H: Responses of metabolic systems to large changes in enzyme activities and effectors. 1. The linear treatment of unbranched chains. Eur J Biochem 213: 613–624, 1993

    Google Scholar 

  32. Small JR, Kacser H: Responses of metabolic systems to large changes in enzyme activities and effectors. 2. The linear treatment of branched pathways and metabolite concentrations. Assessment of the general non-linear case. Eur J Biochem 213: 625–640, 1993

    Google Scholar 

  33. Small JR, Kacser H: A method for increasing the concentration of a specific internal metabolite in steady-state systems. Eur J Biochem 226: 649–656, 1994

    Google Scholar 

  34. Bohnensack R: Control of energy transformation in mitochondria: Analysis by a quantitative model. Biochim Biophys Acta 634: 201–218, 1981

    Google Scholar 

  35. Bohnensack R, Kuster U, Letko G: Rate-controlling steps of oxidative phosphorylation in rat liver mitochondria; a synoptic approach of model and experiment. Biochim Biophys Acta 680: 271–280, 1982

    Google Scholar 

  36. Korzeniewski B, Mazat J-P: Theoretical studies on control of oxidative phosphorylation in muscle mitochondria at different energy demands and oxygen concentrations. Acta Biotheoretica 44: 263–269, 1996

    Google Scholar 

  37. Taylor WM, Van de Pol E, Bygrave FL: On the stimulation of respiration by α-adrenergic agonists in perfused rat liver. Eur J Biochem 155: 319–322, 1986

    Google Scholar 

  38. Kimura S, Suzaki T, Kobayashi S, Abe K, Ogata E: Effects of glucagon on the redox states of cytochromes in mitochondria in situ in perfused rat liver. Biochem Biophys Res Comm 119: 212–219, 1984

    Google Scholar 

  39. Strzelecki T, Thomas JA, Koch CD, LaNoue KF: The effect of hormones on proton compartmentation in hepatocytes. J Biol Chem 259: 4122–4129, 1984

    Google Scholar 

  40. Titheridge MA, Haynes RC: The hormonal stimulation of ureogenesis in isolated hepatocytes through increases in mitochondrial ATP production. Arch Biochem Biophys 201: 44–55, 1980

    Google Scholar 

  41. Quinlan PT, Halestrap AP: The mechanism of the hormonal activation of respiration in isolated hepatocytes and its importance in the regulation of gluconeogenesis. Biochem J 236: 789–800, 1986

    Google Scholar 

  42. Brand MD, Murphy MP: Control of electron flux through the respiration chain in mitochondria and cells. Biol Rev 62: 141–193, 1987

    Google Scholar 

  43. Tager JM, Groen AK, Wanders RJA, Duszyriski J, Westerhoff HV, Vervoorn RC: Control of mitochondrial respiration in rat-liver cells. In: RA Harris, NW Cornell (eds). Isolation characterization and use of hepatocytes. Elsevier, Amsterdam, 1983, pp 313–322

    Google Scholar 

  44. Korzeniewski B, Harper M-E, Brand M: Proportional activation coefficients during stimulation of oxidative phosphorylation by lactate and pyruvate or by vasopressin. Biochim Biophys Acta 1229: 315–322, 1995

    Google Scholar 

  45. Akerboom TM, Bookelman H, Tager JM: Control of ATP transport across the mitochondrial membrane in isolated rat-liver cells. FEBS Lett 74: 50–54, 1977

    Google Scholar 

  46. Lemasters JJ, Sowers AK: Phosphate dependence of and actractyloside inhibition of mitochondrial oxidative phosphorylation. J Biol Chem 254: 1248–1251, 1979

    Google Scholar 

  47. Ereciäska M, Stubbs M, Miyata Y, Ditre CM, Wilson DF: Regulation of cellular metabolism by intracellular phosphate. Biochim Biophys Acta 462: 20–35, 1977

    Google Scholar 

  48. Hassinen JE: Mitochondrial respiratory control in the myocardium. Biochim Biophys Acta 853: 135–151, 1986

    Google Scholar 

  49. Atkinson DE: The energy charge of the adenylate pool as a regulatory parameter. Interaction with feedback modifiers. Biochemistry 7: 4030–4034, 1968

    Google Scholar 

  50. Korzeniewski B: What regulates respiration in mitochondria? Biochem Molec Biol Int 39: 415–419, 1996

    Google Scholar 

  51. Denton RM, McCormack JG: On the role of the calcium cycle in heart and other mammalian mitochondria. FEBS Lett 119: 1–8, 1980

    Google Scholar 

  52. Hansford RG: Control of mitochondrial substrate oxidation. Curr Top Bioenerg 10: 217–278, 1980

    Google Scholar 

  53. McCormack JG, Halestrap AP, Denton RM: Role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physiol Rev 70: 391–425, 1990

    Google Scholar 

  54. McCormack JG, Denton RM: The role of mitochondrial Ca2+ transport and matrix Ca2+ in signal transduction in mammalian tissues. Biochim Biophys Acta 1018: 287–291, 1990

    Google Scholar 

  55. Harris DA, Das AM: Control of mitochondrial ATP synthesis in the heart. Biochem J 280: 561–573, 1991

    Google Scholar 

  56. Moreno-Sanchez R, Hogue BA, Hansford RG: Influence of NAD-linked dehydrogenase activity on flux through oxidative phosphorylation. Biochem J 268: 421–428, 1990

    Google Scholar 

  57. Balaban RS, Kantor HL, Katz LA, Briggs RW: Relation between work and phosphate metabolite in the in vivo paced mammalian heart. Science 232: 1121–1123, 1986

    Google Scholar 

  58. Katz LA, Swain JA, Portman MA, Balaban RS: Relation between phosphate metabolites and oxygen consumption of heart in vivo. Am J Physiol 256: H265–H274, 1989

    Google Scholar 

  59. Balaban RS, Heineman FW: Control of mitochondrial respiration in the heart in vivo. Mol Cell Biochem 89: 191–197, 1989

    Google Scholar 

  60. Heineman FW, Balaban RS: Control of mitochondrial respiration in the heart in vivo. Annu Rev Physiol 52: 523–542, 1990

    Google Scholar 

  61. Kacser H, Acerenza L: A universal method for achieving increases in metabolite production. EurJ Biochem 216: 361–367, 1993

    Google Scholar 

  62. Korzeniewski B: Regulation of ATP supply during muscle contraction. Biochem (in press)

  63. Krämer R, Mayr U, Heberger C, Tsompanidou S: Activation of the ADP/ATP carrier from mitochondria by cationic effectors. Biochim Biophys Acta 855: 201–210, 1986

    Google Scholar 

  64. Korzeniewski B, Froncisz W: Thermodynamic response paradigm and its application to oxidative phosphorylation. In: S Schuster, M Rigoulet, R Ouabi, J-P Mazat (eds). Modern Trends in BioThermoKinetics. Plenum Press, New York, 1993, pp 33–38

    Google Scholar 

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Korzeniewski, B. Is it possible to predict any properties of oxidative phosphorylation in a theoretical way?. Mol Cell Biochem 184, 345–358 (1998). https://doi.org/10.1023/A:1006881618134

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