The Creatine Kinase Phosphotransfer Network: Thermodynamic and Kinetic Considerations, the Impact of the Mitochondrial Outer Membrane and Modelling Approaches

  • Valdur Saks
  • Tuuli Kaambre
  • Rita Guzun
  • Tiia Anmann
  • Peeter Sikk
  • Uwe Schlattner
  • Theo Wallimann
  • Mayis Aliev
  • Marko Vendelin
Part of the Subcellular Biochemistry book series (SCBI, volume 46)


In this review, we summarize the main structural and functional data on the role of the phosphocreatine (PCr) -- creatine kinase (CK) pathway for compartmentalized energy transfer in cardiac cells. Mitochondrial creatine kinase, MtCK, fixed by cardiolipin molecules in the vicinity of the adenine nucleotide translocator, is a key enzyme in this pathway. Direct transfer of ATP and ADP between these proteins has been revealed both in experimental studies on the kinetics of the regulation of mitochondrial respiration and by mathematical modelling as a main mechanism of functional coupling of PCr production to oxidative phosphorylation. In cells in vivo or in permeabilized cells in situ, this coupling is reinforced by limited permeability of the outer membrane of the mitochondria for adenine nucleotides due to the contacts with cytoskeletal proteins. Due to these mechanisms, at least 80% of total energy is exported from mitochondria by PCr molecules. Mathematical modelling of intracellular diffusion and energy transfer shows that the main function of the PCr -- CK pathway is to connect different pools (compartments) of ATP and, by this way, to overcome the local restrictions and diffusion limitation of adenine nucleotides due to the high degree of structural organization of cardiac cells


Creatine Kinase Oxidative Phosphorylation Mitochondrial Outer Membrane Adenine Nucleotide Adenylate Kinase 
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Copyright information

© Springer 2007

Authors and Affiliations

  • Valdur Saks
    • 1
    • 2
  • Tuuli Kaambre
    • 2
  • Rita Guzun
    • 1
  • Tiia Anmann
    • 2
  • Peeter Sikk
    • 2
  • Uwe Schlattner
    • 1
    • 3
  • Theo Wallimann
    • 3
  • Mayis Aliev
    • 4
  • Marko Vendelin
    • 5
  1. 1.Laboratory of Fundamental and Applied Bioenergetics, INSERM U 884Joseph Fourier University2280, Rue de la PiscineFrance
  2. 2.Laboratory of BioenergeticsNational Institute of Chemical Physics and BiophysicsAkadeemia tee 23Estonia
  3. 3.Institute of Cell BiologyETH-Zurich, Hönggerberg HPM D24Switzerland
  4. 4.Laboratory of Cardiac PathologyCardiology Research Center, Institute of Experimental Cardiology121552 MoscowRussia
  5. 5.Department of Mechanics and Applied Mathematics, Institute of CyberneticsTallinn Technical UniversityAkadeemia tee 21Estonia

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