The discovery of functional compartmentation of creatine kinase on the mitochondrion and myofibril established a molecular basis for a phosphorylcreatine-creatine shuttle for energy transport in muscle.
This review outlines the historical and biochemical evidence establishing the phosphorylcreatine-creatine shuttle as the primary mechanism for energy transport in heart and skeletal muscle.
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.
Bessman et al. (Fri,) conducted a review in Muscle energy transport. The discovery of functional compartmentation of creatine kinase on the mitochondrion and myofibril established a molecular basis for a phosphorylcreatine-creatine shuttle for energy transport in muscle.