Glycogen Definition
Glycogen, a large, branched-branched polysaccharide, is the main form of glucose storage in humans and animals. Glycogen serves as an energy reserve. When energy is needed by the body glycogen is broken down into glucose. This glucose then enters the glycolytic pathway or pentosephosphate pathway and is released into bloodstream. Glycogen, a form of glucose storage in bacteria and fungi, is also important.
Glycogen Structure
Glycogen, a branched glucose polymer, is called. The linear linkage of glucose residues is by a-1.4 glycosidic links. Approximately every ten residues, a chain made up of glucose residues, branches off via a-1.6 glycosidic linkages. A helical polymer structure is formed by the a-glycosidic links. Glycogen can be hydrated with 3 to 4 parts water. This forms granules that measure 10-40nm in size in the cytoplasm. Each glycogen granule contains the core of glycogenin, which plays a role in glycogen production. Glycogen, an analogue to starch, is the main form for glucose storage in most plants. However, starch has fewer branches than glycogen and is more compact than glycogen.
These figures show the structure of glycogen. The green circles are the a-1.6 linkages at branch point, while the red circles represent non-reducing ends of the chain.
Glycogen Function
Glycogen is found in the liver and muscle cells of both animals and humans. Glycogen is a sugar-derived compound that can be synthesized when blood glucose levels are high. It also serves as a source of glucose for tissues in the body when glucose levels drop.
Liver cells
Glycogen accounts for 6-10% to 10% of the liver’s weight. Insulin released from the pancreas stimulates glucose uptake into the liver cells by increasing blood glucose levels after food is consumed. Glycogen synthase and other enzymes involved with glycogen synthesis are activated by insulin. Glycogen chains can be lengthened by adding glucose molecules to glucose levels that are sufficient. This process is called glyconeogenesis. Glycogen synthesis stops when glucose and insulin levels drop. Glycogen synthesis ceases when blood glucose levels drop below a certain point. This is because glucagon, which is released by the pancreas, signals liver cells to breakdown glycogen. Glycogen can be broken down by glycogenolysis to glucose-1-phosphate. This is then converted into glucose and released into your bloodstream. Glycogen acts as a buffer for blood glucose levels, storing glucose when it is high and releasing glucose when it is low. Glycogen is broken down in the liver to supply glucose for the body’s energy needs. Cortisol and epinephrine are also stimulators of glycogen breakdown.
Muscle cells
Glycogen, which is a fraction of the muscle’s weight, only makes up 1-2% of liver cells. The body’s greater muscle mass means that the glycogen in muscle is more than the liver. Muscle is also different from liver in that it only provides glucose to its own cells. Muscle cells do not express the enzyme glucose-6-phosphatase, which is required to release glucose into the bloodstream. The glucose-1-phosphate, which is formed from glycogen degradation in muscle fibers, is converted into glucose-6-phosphate. This provides energy for the muscle during exercise or when it responds to stress such as the fight-or flight response.
Other Tissues
Glycogen is found in small amounts in liver and muscle. Glycogen is also used to store glucose within the uterus, which provides energy for the embryo.
Fungi and Bacteria
Glycogen is a major energy storage form. Microorganisms have mechanisms to store energy in order to deal with limited resources. Low levels of nutrient (low levels carbon, phosphorus or nitrogen) can stimulate yeast’s glycogen production. However, bacteria synthesize glycogen when there is a limited supply of carbon energy. Glygen accumulation has also been linked to yeast sporulation and Bacterial Growth.
Glycogen homeostasis, which is highly controlled and allows the body’s glucose to be stored or released depending on its energy needs, is a highly controlled process. Glycogenolysis or glycogen degradation are the two main steps in glucose metabolism.
Glycogenesis
Glycogen production requires energy. Uridine triphosphate is the source of this energy. Hexokinases and glucokinases first phosphorylate glucose to form glucose-6phosphate. This is then converted to glucose-1-phosphate via phosphoglucomutase. UTP-glucose-1-phosphate uridylyltransferase then catalyzes the activation of glucose, in which UTP and glucose-1-phosphate react to form UDP-glucose. The protein glycogenin is responsible for attaching UDP-glucose directly to itself in de novo glycogen synthesis. Glycogenin, a homodimer that contains a tyrosine in each subunit, acts as an anchor point or attachment point for glucose. To form a chain of eight glucose molecules, additional glucose molecules are added to the reducing ends of the previously mentioned glucose molecule. Glycogen synthase adds glucose to the chain via a-1.4 glycosidic linkages.
Branching is catalyzed by amylo-(1,4 to 1,6)-transglucosidase, also called the glycogen branching enzyme. The glycogen branching enzyme transfers six to seven glucose molecules fragments from the end of a chain, to the C6 of a glucose mole located further inside the glycogen molecule. This creates a-1,6 glycosidic linking.
Glycogenolysis
Glycose-1-phosphate is obtained by glycogen phosphorylase. This enzyme phosphorolytically removes one glucose molecule from the non-reducing end. Glycogen-1-phosphate is converted to glucose-6 phosphate by enzyme phosphoglucomutase. Phosphoglucomutase transfers a phosphate group from a phosphorylated serine residue within the active site to C6 of glucose-1-phosphate, producing glucose-1,6-bisphosphate. The active site serine in phosphoglucomutase then attaches the glucose C1 phosphate to it, and glucose-6-phosphate can be released.
Glycogen phosphorylase is not able to cleave glucose from branch points; debranching requires amylo-1,6-glucosidase, 4-a-glucanotransferase, or glycogen debranching enzyme (GDE), which has glucotransferase and glucosidase activities. Glycogen phosphorylase cannot remove the glucose residues of about four branches. GDE removes the last three residues from a branch, attaches them at C4 of the glucose molecule at the tip of another branch, and then removes the last a-1,6-linked sugar residue. GDE doesn’t remove the a-1.6-linked glucose from the branch points phosphorylytically. This means that no glucose is released. This free glucose could in theory be released from muscle into the bloodstream without the action of glucose-6-phosphatase; however this free glucose is rapidly phosphorylated by hexokinase, preventing it from entering the bloodstream.
The glucose-6-phosphate resulting from glycogen breakdown may be converted to glucose by the action of glucose-6-phosphatase and released into the bloodstream. This happens in the liver, kidney, intestine and kidney. However, it does not occur in muscle where this enzyme is missing. The glycolytic pathway in muscle allows glucose-6-phosphate to enter the cell and provide energy. The pentose-phosphate pathway may also be able to take glucose-6-phosphate, which results in the production NADPH and five other carbon sugars.
Exercise and Glycogen depletion
Glycogen depletion is a condition in which glycogen is removed from muscle during endurance training. This can cause severe fatigue and make it difficult to move. Glycogen loss can be reduced by consuming carbohydrates that have a high glycemic (high rate at which blood glucose is converted to glucose) while exercising. This will replace some of the glucose used during exercise. You may also find special exercise programs that help you use fatty acids more efficiently as an energy source. This will allow you to break down less glycogen. To increase glycogen storage, athletes may use carbohydrate loading. This is the intake of large quantities of carbohydrates.
Glycogen storage diseases: Examples
Two main types of glycogen storage diseases exist: those that result from defective glycogen homeostasis, which is found in the liver, and those that are caused by defective glycogen homeostasis, which is found in the muscles. Defective liver glycogen storage can lead to cirrhosis (liver damage), hepatomegaly, hypoglycemia and enlarged livers. Myopathies and metabolic impairment are common consequences of defective muscle glycogen storage. Glycogen storage diseases include McArdle Disease and Pompe Disease.
Pompe Disease
Mutations in the GAA gene that encodes acid maltase (lysosomal acids a-glucosidase) are responsible for Pompe disease. Acid maltase plays a role in glycogen degradation, and disease-causing mutations can lead to a detrimental buildup in glycogen. There are three forms of Pompe Disease. The adult, juvenile, and infantile are all more severe. If left untreated, the infantile form can cause death within one to two years.
McArdle Disease
McArdle disease is caused by mutations within the PYGM gene. This gene encodes myophosphorylase which is a glycogen phosphorylase Ioform found in muscle. Although symptoms are common in children, the disease can be difficult to diagnose in adulthood. The disease can cause muscle pain, fatigue, and even death if it is not treated properly.
Andersen Disease
Andersen Disease is caused when there is a mutation in the GBE1 genes, which encodes glycogen branching and affects liver and muscle. The symptoms are typically noticed in the first few months of life and can include stunted growth and liver enlargement. The disease can cause serious complications that could lead to death.
Quiz
1. Which function best describes glycogen’s functionality?
A. A.
B. B.
C. Stores glucose for plants
D. It buffers blood glucose levels and acts as an energy source that can be readily mobilized
D is correct. Glycogen, the main form for glucose storage in humans and animals, is correct. Glycogen can be synthesized when blood glucose levels rise and is broken down when they fall. It serves as a buffer for blood glucose levels. Glycogen is a vital energy source for cells and organisms. It provides glucose to all tissues in the body. 2. What hormone stimulates glycogen metabolism?
A. Glucagon
B. Thyroid
C. Insulin
D. Estrogen
A is correct. Low blood sugar triggers the release of glucagon which stimulates glycogen’s breakdown. Insulin is produced when there is high blood sugar. It stimulates glucose uptake as well as glycogen synthesis.
3. What is the fate of the glucose-1-phosphate that is produced by glycogenolysis
A. A.
B. B.
C. Conversion of glucose to glucose and subsequent release into the bloodstream
D. All of the Above
D is correct. D is correct. In liver cells, glucose-6-phosphate is converted to glucose by glucose-6-phosphatase and released into the bloodstream.
Refer to
> * Eicke S., Seung D.., Egli B.., Devers E.A. and Streb S. (2017). “Increasing the plant’s carbohydrate storage capability by engineering a glycogen like polymer pool within the cytosol.” Metabolic Engineering. 40:23-32.
* Hargreaves, M. and Richter, E.A. (1988). “Regulation of skeletal muscles glycogenolysis during exercise.” Canadian Journal of Sport Sciences. 13(4): .
* Ivy, J.L. (1991). Sports Medicine. 11(1):6-19.
