Question

Outline the unique hormonal regulation for glycogen degradation in liver and muscle. Also, include the roles of insulin, glucagon, and Epinephrine in your answer. (Flow chart is acceptable)

Answer 1

Glycogen

Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body.

Glycogen provides an additional source of glucose besides that produced via gluconeogenesis. Because glycogen contains so many glucoses, it acts like a battery backup for the body, providing a quick source of glucose when needed and providing a place to store excess glucose when glucose concentrations in the blood rise. The branching of glycogen is an important feature of the molecule metabolically as well. Since glycogen is broken down from the "ends" of the molecule, more branches translate to more ends, and more glucose that can be released at once. Liver and skeletal muscle are primary sites in the body where glycogen is found.

Phosphorolysis of alpha-1,4-glycosidic bonds of glycogen to release glucose-1-phosphate sequentially from the non-reducing end by glycogen phosphorylase:

• In vivo, [P_i] is about 100-fold higher than [glucose 1-phosphate], preventing reversal
• The muscle and liver phosphorylase isoforms are distinct.
• Glucose-binding causes a conformation change in the active phosphorylated liver "a" isoform, exposing an activating phosphate group to the enzymatic activity of protein phosphatase 1, which removes the activating phosphate, thereby regenerating the inactive, unphosphorylated "b" form of the enzyme. Thus, in liver, glycogen breakdown by glycogen phosphorylase is regulated by the glucose concentration, consistent with the function of the liver, to ensure that glucose is provided to other tissues.
• The muscle isoform of phosphorylase b can be activated by the binding of AMP, which is present in increased concentrations when the energy charge of the cell is low. ATP and glucose-6-phosphate reverse the activation by AMP by competing for the AMP binding site. Thus, in muscle, glycogen breakdown catalyzed by glycogen phosphorylase is regulated by the energy charge of the cell, consistent with the function of muscle glycogen to act as an energy store to be mobilized to supply energy for muscle contraction. The liver isoform of phosphorylase b is not activated by AMP.
• glycogen phosphorylase degrades linear glycogen in which the glucose units are linked by α 1,4 glycosidic bonds, to within 4 glucose units of an α 1,6 glycosidic branch, at which point glycogen phosphorylase stops

Insulin stimulates the liver to store glucose in the form of glycogen. A large fraction of glucose absorbed from the small intestine is immediately taken up by hepatocytes, which convert it into the storage polymer glycogen. Insulin has several effects in liver which stimulate glycogen synthesis.

Epinephrine markedly stimulates glycogen breakdown in muscle and, to a lesser extent, in the liver. The liver is more responsive to glucagon, a polypeptide hormone that is secreted by the α cells of the pancreas when the blood-sugar level is low.