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Molecular System Bioenergics of the Heart: Experimental Studies of Metabolic Compartmentation and Energy Fluxes versus Computer Modeling†
Institute of Experimental Cardiology, Cardiology Research Center, Moscow, 121552, Russia
INSERM U1055, Laboratory of Fundamental et Applied Bioenergetics, Joseph Fourier University, 2280 Rue de la Piscine, BP 53, Grenoble Cedex 9, France
Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618 Tallinn, Estonia
Professor emeritus, formerly at Institute of Cell Biology ETH Zurich
† This work is dedicated to the memory of Professor Xavier Leverve. Professor Xavier Leverve (born in 1950) created the Laboratory of Fundamental and Applied Bioenergetics at the Joseph Fourier University in Grenoble, France, in 1995. He was one of the leading scientists in the field of bioenergetics, metabolism and nutrition. His interests were covering cellular bioenergetics and substrate metabolism, as well as hypoxia/reoxygenation and acid/base balance. Under his leadership, the Laboratory of Fundamental and Applied Bioenergetics of Joseph Fourier University became one of the most productive and influential in France, acknowledged for its high level of research by acceptance into Institute National de la Santé et la Recherche Medicale (INSERM) in 2002. He directed this laboratory very effectively and skillfully until the end of his days on November 8, 2010. He will always be missed.
* Author to whom correspondence should be addressed.
Received: 10 November 2011; in revised form: 30 November 2011 / Accepted: 30 November 2011 / Published: 13 December 2011
Abstract: 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.
Keywords: heart; respiration; energy transfer; phosphocreatine; mathematical modeling
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Aliev, M.; Guzun, R.; Karu-Varikmaa, M.; Kaambre, T.; Wallimann, T.; Saks, V. Molecular System Bioenergics of the Heart: Experimental Studies of Metabolic Compartmentation and Energy Fluxes versus Computer Modeling. Int. J. Mol. Sci. 2011, 12, 9296-9331.
Aliev M, Guzun R, Karu-Varikmaa M, Kaambre T, Wallimann T, Saks V. Molecular System Bioenergics of the Heart: Experimental Studies of Metabolic Compartmentation and Energy Fluxes versus Computer Modeling. International Journal of Molecular Sciences. 2011; 12(12):9296-9331.
Aliev, Mayis; Guzun, Rita; Karu-Varikmaa, Minna; Kaambre, Tuuli; Wallimann, Theo; Saks, Valdur. 2011. "Molecular System Bioenergics of the Heart: Experimental Studies of Metabolic Compartmentation and Energy Fluxes versus Computer Modeling." Int. J. Mol. Sci. 12, no. 12: 9296-9331.