8.1 Mechanisms and Modeling of Energy Transfer Between Intracellular Compartments

Saks, Valdur; Vendelin, Marko; Aliev, Mayis; Kekelidze, Téa; Engelbrecht, Jüri

doi:10.1007/978-0-387-30411-3_30

Cited by 13 publications

(26 citation statements)

References 201 publications

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“…This is due to the significant heterogeneity and local restrictions in the diffusion of adenine nucleotides in cells and to the necessity of rapid removal of ADP from the vicinity of Mg-ATPases to avoid their inhibition by the accumulating product MgADP. As is described in many chapters of this book, not only is ATP delivered by diffusion but also intracellular energy transfer is facilitated via networks consisting of phosphoryl group-transferring enzymes such as creatine kinase (CK), adenylate kinase (AK), and glycolytic phosphoryl-transferring enzymes [39,[87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105]. Most important among them is the creatine kinase system.…”

Section: Unitary (Modular) Organization Of Energy Metabolism and Compmentioning

confidence: 99%

“…Specific mitochondrial CK isoenzymes (MtCK), called ubiquitous (uMtCK) and sarcomeric (sMtCK), are functionally coupled to oxidative phosphorylation and produce PCr from mitochondrial ATP. PCr in turn is used for local regeneration of ATP by the muscle cytoplasmic isoform of CK (M-CK), driving myosin ATPases or ion pump ATPases [87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105]. Recent studies in CKdeficient transgenic animals indicate that energy transfer and communication between ATP-generating and ATP-utilizing sites within a muscle cell do not rely exclusively upon the activity of CK but rather may include a number of additional intracellular phosphotransfer systems such as AK and glycolysis [106][107][108][109][110][111].…”

Section: Unitary (Modular) Organization Of Energy Metabolism and Compmentioning

confidence: 99%

“…ICEUs are analogous to calcium release units (CRUs), structurally organized sites of Ca 2þ microdomains (Ca 2þ sparks) that form a discrete, stochastic system of intracellular calcium signaling in cardiac cells [115,116]. The structural organization of ICEUs results in local confinement of adenine nucleotides and Cr-PCr couples in discrete dynamic energetic circuits between actomyosin ATPases and mitochondrial ATPsynthases [90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106]. Similar discrete microdomains in cardio- The scheme shows the structural organization of the energy transfer networks of coupled CK and AK reactions within an ICEU.…”

Section: Unitary (Modular) Organization Of Energy Metabolism and Compmentioning

confidence: 99%

“…However, the role of the CK system in brain cells has been investigated to a much lesser extent than in cardiac cells [103,105,[236][237][238], likely due to the high degree of tissue heterogeneity. In our recent studies we adopted the method of Clark for purification of rat brain synaptosomes and synaptosomal mitochondria.…”

Section: Creatine Kinase System In Brain Cellsmentioning

confidence: 99%

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Integrated and Organized Cellular Energetic Systems: Theories of Cell Energetics, Compartmentation, and Metabolic Channeling

Saks

Monge

Anmann

et al. 2007

Molecular System Bioenergetics

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Bioenergetics as a part of biophysical chemistry and biophysics is a quantitative science that is based on several fundamental theories. The definition of energy itself is given by the first law of thermodynamics, and application of the second law of thermodynamics shows that living cells can function as open systems only where the internal order (low entropy state) is maintained due to increasing the entropy in the surrounding medium (Schrödinger's principle of negentropy). For this, the exchange of mass is needed, which gives rise to metabolism as the sum of catabolism and anabolism, and the free energy changes during catabolic reactions supply energy for all cellular work -osmotic, mechanical, and biochemical. The free energy changes during metabolic reactions obey the rules of chemical thermodynamics, which deals with Gibbs free energy of chemical reactions and with electrochemical potentials. For application of these theories to the integrated systems in vivo, complex cellular organization should be accounted for: macromolecular crowding; metabolic channeling and functional coupling mechanisms due to close and tight protein-protein interactions; compartmentation of the enzymes due to their attachment to the subcellular membranes or connection to the cytoskeleton; and both macro-and microcompartmentation of substrates and metabolites in the cells. Because of this, almost all processes important for cell life are localized within small areas of the cell, and for their integration effective systems of communication, including compartmentalized energy transfer systems, are required. These are represented in muscle cells by the phosphotransfer networks, mostly by the creatine kinase and adenylate kinase systems, whose alterations under ischemic conditions contribute significantly to acute ischemic contractile failure of the heart. 59 Molecular System Bioenergetics: Energy for Life. Edited by Valdur Saks

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Section: Unitary (Modular) Organization Of Energy Metabolism and Compmentioning

confidence: 99%

Section: Unitary (Modular) Organization Of Energy Metabolism and Compmentioning

confidence: 99%

Section: Unitary (Modular) Organization Of Energy Metabolism and Compmentioning

confidence: 99%

Section: Creatine Kinase System In Brain Cellsmentioning

confidence: 99%

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Integrated and Organized Cellular Energetic Systems: Theories of Cell Energetics, Compartmentation, and Metabolic Channeling

Saks

Monge

Anmann

et al. 2007

Molecular System Bioenergetics

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“…These results and their interpretation, made in the work referred to above, are not consistent with a large body of existing data, including Vendelin’s own results published before in many articles [9,102,104]. They raise many questions among specialists in the field that worked on the very question of how in cardiac muscle cells energy is transferred from mitochondria to the contractile apparatus, ultimately supporting cardiac muscle contraction.…”

Section: Introductionmentioning

confidence: 71%

Molecular System Bioenergics of the Heart: Experimental Studies of Metabolic Compartmentation and Energy Fluxes versus Computer Modeling

Aliev

Guzun

Karu-Varikmaa

et al. 2011

IJMS

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In this review we analyze the recent important and remarkable advancements in studies of compartmentation of adenine nucleotides in muscle cells due to their binding to macromolecular complexes and cellular structures, which results in non-equilibrium steady state of the creatine kinase reaction. We discuss the problems of measuring the energy fluxes between different cellular compartments and their simulation by using different computer models. Energy flux determinations by 18O transfer method have shown that in heart about 80% of energy is carried out of mitochondrial intermembrane space into cytoplasm by phosphocreatine fluxes generated by mitochondrial creatine kinase from adenosine triphosphate (ATP), produced by ATP Synthasome. We have applied the mathematical model of compartmentalized energy transfer for analysis of experimental data on the dependence of oxygen consumption rate on heart workload in isolated working heart reported by Williamson et al. The analysis of these data show that even at the maximal workloads and respiration rates, equal to 174 μmol O2 per min per g dry weight, phosphocreatine flux, and not ATP, carries about 80–85% percent of energy needed out of mitochondria into the cytosol. We analyze also the reasons of failures of several computer models published in the literature to correctly describe the experimental data.

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Integrated and Organized Cellular Energetic Systems

Saks

Monge

Guzun

et al. 2009

Wiley Encyclopedia of Chemical Biology

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Bioenergetics as a part of biophysical chemistry and biophysics is a quantitative science that is based on several fundamental theories. The definition of energy itself is given by the first law of thermodynamics, and application of the second law of thermodynamics shows that the living cells can only function as open systems in which internal order (low entropy state) is maintained by increasing the entropy in surrounding medium (Schrödinger's principle of negentropy). For this mechanism, exchange of mass is needed that yields metabolism as the sum of catabolism and anabolism. The free‐energy changes taking place during metabolic reactions obey rules of chemical thermodynamics, which deals with Gibbs free energy of chemical reactions and with electrochemical potentials. For application of these theories to the integrated systems in vivo , complex cellular organization should be accounted for: macromolecular crowding, metabolic channeling and functional coupling mechanisms caused by close and tight protein–protein interactions, compartmentation of enzymes, as well as both macrocompartmentation and microcompartmentation of substrates and metabolites in cells should be considered. For integration of these system components, effective methods of communication, including compartmentalized energy transfer systems, are required. These systems are represented in muscle cells by phosphotransfer networks, mostly by creatine kinase and adenylate kinase systems. System analysis of these networks shows their central role both in energy transfer and metabolic feedback regulation of mitochondrial function, in regulation of ion fluxes and cellular energetics during increased workload by synchronizing the cellular electrical and mechanical activities with energy supply and substrate oxidation.

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8.1 Mechanisms and Modeling of Energy Transfer Between Intracellular Compartments

Cited by 13 publications

References 201 publications

Integrated and Organized Cellular Energetic Systems: Theories of Cell Energetics, Compartmentation, and Metabolic Channeling

Integrated and Organized Cellular Energetic Systems: Theories of Cell Energetics, Compartmentation, and Metabolic Channeling

Molecular System Bioenergics of the Heart: Experimental Studies of Metabolic Compartmentation and Energy Fluxes versus Computer Modeling

Integrated and Organized Cellular Energetic Systems

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