title: The creatine kinase phosphotransfer network: thermodynamic and kinetic considerations, the impact of the mitochondrial outer membrane and modelling approaches.
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.
authors.affiliation: Laboratory of Fundamental and Applied Bioenergetics, INSERM U 884, Joseph Fourier University, 2280, Rue de la Piscine, BP53X-38041, Grenoble Cedex 9, France.
authors.forename: Valdur
authors.initials: V
authors.lastname: Saks
authors.forename: Tuuli
authors.initials: T
authors.lastname: Kaambre
authors.forename: Rita
authors.initials: R
authors.lastname: Guzun
authors.forename: Tiia
authors.initials: T
authors.lastname: Anmann
authors.forename: Peeter
authors.initials: P
authors.lastname: Sikk
authors.forename: Uwe
authors.initials: U
authors.lastname: Schlattner
authors.forename: Theo
authors.initials: T
authors.lastname: Wallimann
authors.forename: Mayis
authors.initials: M
authors.lastname: Aliev
authors.forename: Marko
authors.initials: M
authors.lastname: Vendelin
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D003402:Creatine Kinase / Q000737:chemistry / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008929:Mitochondria, Heart / Q000737:chemistry / Q000201:enzymology*; D000226:Mitochondrial ADP, ATP Translocases / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology*; D010101:Oxygen Consumption / Q000502:physiology; D010725:Phosphocreatine / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D010725:Phosphocreatine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D003402:Creatine Kinase