Control of Glycogen Metabolism and Phosphorylase Kinase. A Model System for Studying Signal Transduction Mechanisms Mediated by Protein Phosphorylation and Ca²⁺

Abstract

One of the best studied metabolic control systems regulates the formation and breakdown of glycogen in mammalian tissues (Huijing, 1975). Glycogen constitutes the main storage form of carbohydrate in mammalian cells and it is the major energy source which sustains ATP levels during muscle contraction. At least 95% of the polymer is located in skeletal muscle and liver, where it plays quite different roles (Cohen, 1976). The rate limiting enzymes in cytosolic glycogenolysis and glycogen synthesis are glycogen phosphorylase and glycogen synthase, while branching and debranching enzymes are considered to be present in excess in normal animals and are therefore not rate-limiting. In this respect, although the current convention regards phosphorylase as a purely degradative enzyme with no synthetic role, it seems possible that intracellular local concentrations of its substrates glucose-1-P and Pi may on occasions favour synthesis (Geddes, 1986). In addition, a potential cellular degradative pathway, concerning cellular glycogen associated with the lysosomal compartments, was also revealed; in this case, the enzyme 1,4-a-glycosidase is responsible for the degradation of the polysaccharide (Geddes, 1986).