Comparative and Evolutionary Aspects of the Control of Phosphorylase

Abstract

The complex nature of the enzymatic control of glycogen breakdown makes this system ideally suited for studies concerned with the evolution of a regulatory mechanism. First, the anaerobic pathway of carbohydrate metabolism must have evolved very early since it is generally assumed that life on Earth emerged under reducing conditions. Indeed, glycolysis is essentially ubiquitous to all forms of life and is found in every species from unicellular organisms to the complex tissues of higher plants and animals. Second, phosphorylase (E. C. 2.4.1.1), which is directly involved in glycogen breakdown, is regulated by both covalent and noncovalent modification, if not also by protein-protein interaction. Covalent control of muscle phosphorylase involves several activating enzymes acting successively on one another, various nucleotides and divalent metal ions, and is closely integrated with other physiological processes since glycolysis is initiated both by hormone release and the nervous stimulation which triggers contraction. As a consequence, the enzyme must contain a variety of sites to account for these multiple interactions. It was therefore surmised that a study of phosphorylase in earlier species might indicate how control of its activity originally arose and evolved with time.

Supported by grants from the National Institutes of Health (AM 07902), the National Science Foundation (GB 20482), and the Muscular Dystrophy Association of America.