Transport of Energy in Muscle: The Phosphorylcreatine Shuttle

Abstract

In order to explain the insulin-like effect of exercise, it was proposed in 1951 that contracting muscle fibers liberate creatine, which acts to produce an acceptor effect--later called respiratory control--on the muscle mitochondria. The development of this notion paralleled the controversy between biochemists and physiologists over the delivery of energy for muscle contraction. With the demonstration of functional compartmentation of creatine kinase on the mitochondrion, it became clear that the actual form of energy transport in the muscle fiber is phosphorylcreatine. The finding of an isoenzyme of creatine phosphokinase attached to the M-line region of the myofibril revealed the peripheral receptor for the mitochondrially generated phosphorylcreatine. This established a molecular basis for a phosphorylcreatine-creatine shuttle for energy transport in heart and skeletal muscle and provided an explanation for the inability to demonstrate experimentally a direct relation between muscle activity and the concentrations of adenosine triphosphate and adenosine diphosphate.

Global cooling: Cold acclimation and the expression of soluble proteins in carp skeletal muscle

“…Multiple isoforms of CK are thought to constitute an intricate transport and energy buffering system, which connects highenergy phosphate production to sites of energy consumption [22,23]. As such CK is involved intimately in the maintenance of cellular energy homeostasis.…”

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.…”

Functional Equivalence of Creatine Kinase Isoforms in Mouse Skeletal Muscle

“…MM-CK and BB-CK are dimers formed from subunits that can also associate to form a muscle-brain (MB) heterodimer that is found in heart. In addition to the cytosolic forms, there are two mitochondrial forms of CK, sarcomeric and ubiquitous mitochondrial CK, which localize to the intermitochondrial membrane space and have been implicated in affecting regulation of oxidative phosphorylation (13)(14)(15)(16). The localization of CK to sites of ATP production and utilization has led to the proposal that CK plays a role in spatial buffering of ATP, ADP, and pH that is important for proper tissue function and in particular, maintaining contractile function in muscle and heart (13)(14)(15)(16).…”