Functional compartmentation of glycogen phosphorylase with creatine kinase and Ca2+ATPase in skeletal muscle

This manuscript discusses aspects of functional compartmentation in the regulation of metabolism. The functional consequences of enzymes coupling between creatine kinase, glycogen phosphorylase and sarcoplasmic reticular Ca2+ ATPase is examined. It is proposed that the coupling of creatine kinase and glycogen phosphorylase classifies as a novel class of diazyme complex with an important regulatory role in the inhibition of glycogenolysis at rest. In addition it is suggested that creatine kinase, glycogen phosphorylase and the sarcoplasmic reticular Ca2+ ATPase may couple to form a three-enzyme complex. From a consideration of the structure and chemical catalysis of the putative three-enzyme complex, a novel net reaction for glycogenolysis in the vicinity of the sarcoplasmic reticulum is suggested (Phosphocreatine+Glycogen+H+◀▶Creatine+Glycogenn−1+Glucose-1-Phosphate). The three-enzyme complex may also have an important role in inhibiting glycogenolysis at rest as well as improving the efficiency of high-energy phosphate transfer.