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

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Creatine and Creatine Kinase in Health and Disease

Part of the book series: Subcellular Biochemistry ((SCBI,volume 46))

Abstract

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

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Authors and Affiliations

  1. Laboratory of Fundamental and Applied Bioenergetics, INSERM U 884, Joseph Fourier University, 2280, Rue de la Piscine, BP53X – 38041Grenoble Cedex 9, France

    Valdur Saks, Rita Guzun & Uwe Schlattner

  2. Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618 Tallinn, Estonia

    Valdur Saks, Tuuli Kaambre, Tiia Anmann & Peeter Sikk

  3. Institute of Cell Biology, ETH-Zurich, Hönggerberg HPM D24, Schafmattstrasse 18, CH-8093 Zurich, Switzerland

    Uwe Schlattner & Theo Wallimann

  4. Laboratory of Cardiac Pathology, Cardiology Research Center, Institute of Experimental Cardiology, 121552 Moscow, Russia

    Mayis Aliev

  5. Department of Mechanics and Applied Mathematics, Institute of Cybernetics, Tallinn Technical University, Akadeemia tee 21, 12618 Tallinn, Estonia

    Marko Vendelin

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  1. Valdur Saks
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  1. VU University Medical Center, Amsterdam, The Netherlands

    Gajja S. Salomons

  2. DSM Nutritional Products Ltd, Basel, Switzerland

    Markus Wyss

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Saks, V. et al. (2007). The Creatine Kinase Phosphotransfer Network: Thermodynamic and Kinetic Considerations, the Impact of the Mitochondrial Outer Membrane and Modelling Approaches. In: Salomons, G.S., Wyss, M. (eds) Creatine and Creatine Kinase in Health and Disease. Subcellular Biochemistry, vol 46. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6486-9_3

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