Question

Describe how the opposing processes of glycogen breakdown and synthesis are reciprocally regulated by allosteric interactions and the covalent modification of key enzymes.

Answer 1

In order to avoid a futile cycle of glycogen synthesis and breakdown simultaneously, cells have evolved an elaborate set of controls that ensure only one pathway is primarily active at a time. Regulation occurs on the enzymes glycogen phosphorylase and glycogen synthase, and involves allosterism, covalent modification of enzymes and, ultimately, hormonal control.

Allosteric factors - ATP, G6P, AMP.

Glycogen phosphorylase is regulated by both allosteric factors and by covalent modification (phosphorylation). Its regulation is consistent with the energy needs of the cell. High energy substrates (ATP, G6P, glucose) inhibit GP, while low energy substrates (AMP, others) activate it. The enzyme uses a cofactor, pyridoxal phosphate (PLP). Regulation of glycogen phosphorylase varies a bit, depending on the tissue in which it is found. For example, the liver makes glucose for the body, but muscles do not and depend on the liver for much of their glucose. Regulation of glycogen breakdown in these tissues is adjusted accordingly, as will be seen.