Hormonal and allosteric regulation of glycogen metabolism

Notes

Glycogen metabolism is regulated by both hormonal and allosteric mechanisms to maintain cellular and whole-body energy homeostasis. Two key enzymes control this process: glycogen synthase, which catalyzes glycogen synthesis, and glycogen phosphorylase, which catalyzes glycogen breakdown. These enzymes are reciprocally regulated, ensuring that glycogen synthesis and degradation do not occur simultaneously. In the fed state, insulin is released in response to elevated blood glucose levels. Insulin binds to its receptor tyrosine kinase (RTK) on the cell membrane, activating the PI3K–Akt signaling pathway. Akt activation leads to stimulation of protein phosphatase-1 (PP1). PP1 removes phosphate groups from target enzymes (dephosphorylation). PP1 dephosphorylates glycogen synthase, converting it into its active form and promoting glycogen synthesis. At the same time, PP1 dephosphorylates and inactivates glycogen phosphorylase and phosphorylase kinase, thereby inhibiting glycogen breakdown and favoring glycogen storage. During fasting, glucagon acts primarily in the liver. Binding of glucagon to a Gs protein-coupled receptor increases intracellular cAMP, which activates protein kinase A ...