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

In addition to gluconeogenesis, the reversible storage of glucose in the form of glycogen provides a second major mechanism of glucose homeostasis.

Glycogen is a branched glucose polymer that is found in many organs, but the largest quantities occur in the liver and in skeletal muscle. The liver can store up to 150–200 grams, which amounts to 10% of the organ’s wet weight. It draws from this reservoir to maintain the blood glucose concentration; glycogen plays a major role in day-to-day glucose homeostasis.

While skeletal muscle contains glycogen at much lower concentration than the liver, its much larger overall mass means that the absolute amount of glycogen stored there is approximately twice higher than in the liver. The contribution of muscle glycogen to glucose homeostasis is less well understood.

While liver and skeletal muscle store the lion’s share of glycogen, it also occurs in other organs such as the heart, the brain, and the kidneys. All of these organs may therefore be affected by glycogen storage diseases (see Section 8.6.

8.2

Glycogen structure

8.2.1

Why store glucose in polymeric form?

The osmotic pressure is governed by the gas equation:

pV=nRT⟺p=nVRT

Glycogen amounts to 10% of the liver’s wet weight, equivalent to 600 mM glucose

When free, 600 mM glucose would triple the osmotic activity of the cytosol—liver cells would swell and burst

Linking 2 (3, …) molecules of glucose divides the osmotic effect by 2 (3, …), permitting storage of large amounts of glucose at physiological osmolarity

The proportionality of concentration and osmotic activity does not strictly apply to large molecules, but the approximation is good enough for the present purpose.

Glycogen synthesis and degradation

Synthesis:

synthesis of an activated precursor, UDP-glucose, by UTP:glucose-1-phosphate uridylyltransferase

initiation of glycogen synthesis by glycogenin

introduction of branches by branching enzyme

chain elongation by glycogen synthase

repeat steps 3 and 4

Degradation:

depolymerization of linear strands by phosphorylase

removal of branches by debranching enzyme

repeat steps 1 and 2

This slide summarizes the enzyme reactions that occur in glycogen synthesis and degradation, respectively. As you can see, the regular, periodic structure of glycogen corresponds to similarly regular and periodic methods of synthesis and breakdown that require only a small number of different enzymes.