A simple analysis of the "phosphocreatine shuttle"

Abstract

The diffusive mobility of solutes chemically connected by reversible reactions in cells is analyzed as a problem of facilitated diffusion. By this term we mean that the diffusive flux of any substance, X, which is in one metabolic pathway, is effectively increased when it participates in a second and equilibrium reaction with another substance Y because the total flux of X in the pathway is the sum of the fluxes of X and Y. This notion is generalized and is seen to include the familiar enhanced intracellular diffusion of oxygen by oxymyoglobin. In this framework the function of creatine kinase (CK) is seen to have two aspects: 1) phosphocreatine (PCr) via the CK reaction buffers the cellular ATP and ADP concentrations and 2) transport of high-energy phosphates is predominantly in the chemical form of PCr. This predominance of PCr is a consequence of the maintained ATP, ADP, and total creatine levels and of the apparent equilibrium constant of the reaction. Thus experimental results demonstrating the transport aspects of the CK reaction emphasize only one feature of a more general notion of facilitated diffusion by near-equilibrium metabolic reactions and do not per se establish the existence of any physical or functional compartmentation of ATP, ADP, PCr, or creatine. PCr can be a large source for increasing inorganic phosphate levels during contractile activity, possibly as a metabolic regulator. Neither the transport nor buffer aspects can be quantitatively important in cells with small distances between ATP-utilizing and ATP-generating sites, such as is the case with cardiac myofibrils and mitochondria.

Dissociated Expression of Mitochondrial and Cytosolic Creatine Kinases in the Human Brain: A New Perspective on the Role of Creatine in Brain Energy Metabolism

“…These hypotheses parallel the well-studied distributions and functions of these enzymes in muscle fibers. 1,14 All aspects of the PCr/CK system are probably used to different degrees in the brain: from spatiotemporal buffering in astrocytes 3,14,20 to directed shuttling of high energy phosphoryls by the phosphocreatine circuit model in neurons. 1,14 Further complexity is expected with a more in-depth study of this and other energetic systems in the brain.…”

“…Theoretical analysis of a system with a cytosolic CK expressed homogeneously within a volume and at near equilibrium points to the ability of such a system to support the buffering of ATP temporally and spatially, the latter via facilitated diffusion. 3 In several 31 P nuclear magnetic imaging (NMR) magnetization transfer studies, the forward and reverse rate constants for CK in the brain are statistically indistinguishable, suggesting that they are near equilibrium. 27,28 Thus, alone, BCK is likely to be mediating the buffering of ATP in the cytosol as it is consumed by energy-intensive processes, and speeding the flux of high-energy phosphoryls around the cell.…”

Magnetization transfer MRS

“…As energy production and consumption occur at different locations with different CK isoforms, this system is also used for energy transport. 38 Phosphocreatine (PCr) is a low molecular weight energy-rich phosphate which migrates between different locations. Therefore, PCr is part of various chemical (metabolic) exchange reactions as well as transport processes, e.g.…”

Introduction toin vivo31P magnetic resonance spectroscopy of (human) skeletal muscle

“…Under aerobic conditions mitochondrial respiration serves as the major source of high-energy phosphate groups such as ATP and PCr. In addition to having a role in balancing ATP levels, the PCr-creatine kinase system is considered to be an efficient intermediate in the transfer of high-energy phosphates from the sites of energy production (mitochondria, glycolytic loci) to the energy-consuming locations in the muscle cell, a potential function which has attracted considerable attention (Bessman & Geiger, 1981;Meyer et al 1984;Walliman et al 1992;Saks & Ventura-Clapier, 1994). Under anaerobic conditions, when glycogenolysis is left as the main energy-generating process, the role of the PCr circuit as a back-up system for preserving the integrity of energy homeostasis becomes clearly evident.…”