Module 7 - Glygogenesis Notes

Hi everyone! In today’s video we’ll be exploring the glycogen degradation pathway.

Glycogen is the storage form of glucose in a wide range of organisms that includes vertebrates and microorganisms. It serves as a reservoir of glucose units for use in glycolysis and energy production in the form of ATP.

Glycogen is composed of glucose units primarily linked by alpha1-4 glycosidic bonds, while branches due to the alpha 1-6 glycosidic linkages, occur roughly every 8 to 10 glucose residues. T

he figure on the left illustrates the structure of glycogen, as well as the two types of glycosidic linkages normally found in this polymer.

In vertebrates, glycogen is primarily stored in the liver and skeletal muscles. Around 1-2% of the muscle mass is attributed to glycogen. Muscle glycogen provides an immediate source of energy for the rapidly contracting muscles, either for aerobic or anaerobic metabolism. During vigorous activities, muscle glycogen may be used up in just an hour or less.

On the other hand, around 10% of the liver mass is attributed to glycogen. Liver glycogen is a quick source of glucose for maintenance of blood-glucose levels. This is important for tissues that require glucose as fuel, especially the brain which cannot use fatty acids as fuel.

The mobilization of glucose from glycogen requires 3 enzymes, namely: glycogen phosphorylase, glycogen-debranching enzyme, and phosphoglucomutase.

Glycogen phosphorylase is an enzyme that catalyzes a phosphorolysis reaction, where an alpha1-4 glycosidic linkage is cleaved due to the attack by an incoming inorganic phosphate or Pi.

You can see the details of the reaction in the figure below.

The enzyme starts at the nonreducing end of glycogen and then successively cleaves the alpha1-4 linkage, thereby releasing the terminal glucose residue in the form of glucose 1-phosphate.

To accomplish this reaction, the enzyme needs a cofactor in the form of pyridoxal phosphate.

Note also that this phosphorolysis reaction is quite different from the hydrolysis reaction catalyzed by the alpha-amylase enzyme during the intestinal digestion of starch and glycogen.

In this reaction, the formation of the phosphate ester in glucose 1-phosphate preserves a portion of the energy originally contained in the glycosidic bond.

Glycogen phosphorylase, however, cannot cleave the alpha1-6 glycosidic linkage in glycogen and its action stops around four residues away from the branched point. In the figure, you can see the four glucose residues from the branch point represented by yellow and red colors.

Another enzyme is needed to remove the alpha1-6 linkage, and this is the debranching enzyme, formally known as oligo (α16) to (α14) glucantransferase. This enzyme removes the branched point by catalyzing two successive reactions that transfer the branches.

The first reaction is to transfer a few glucose residues (colored yellow) from one branch to another. The second reaction hydrolyzes the (α16) linkage, leaving behind (α14) linked glucosyl residues. Glycogen phosphorylase again continues its activity.

The last enzyme is phosphoglucomutase. This enzyme catalyzes the interconversion of glucose 1-phosphate to glucose 6-phosphate. The glucose 6-phosphate from this reaction may have different fates depending on the tissue involved.

In the liver, an enzyme known as glucose 6-phosphatase removes the phosphate from glucose 6-phosphate and the remaining glucose product is then released into the blood to maintain the blood glucose levels between meals.

In the muscle, glucose 6-phosphate directly enters the glycolytic pathway where it undergoes further oxidation coupled with the production of energy to support muscle contraction.

The regulation of the pathway depends on the metabolic state of the tissue involved. For instance, in the liver during periods of starvation, the body increases the secretion of the hormone glucagon in the blood and cyclic AMP (cAMP) in tissues. This will ultimately promote glycogen degradation, which helps to increase blood glucose levels. O

n the other hand, during fed state when blood glucose levels rise, the body begins to increase secretion of the hormone insulin in the blood. Blood and tissue glucose levels also rise indicating the availability of fuel, and tissue levels of cAMP begin to drop, resulting in the lowering of glycogen degradation.

For both liver and muscle, during periods of exercise and stress, blood levels of the hormone epinephrine increase, and tissue levels of cAMP and Ca2+-calmodulin complex also increase, favoring the mobilization of glucose from glycogen. This will allow glucose to be used as fuel for the contracting muscles.