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Glycogen

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Structure and Functions of Glycogen

Glycogen is a polysaccharide (abundant carbohydrate) of glucose that serves as a source to store energy in fungi and animals. The polysaccharide structure of glucose gives the basic storage form of glucose in the body. Glycogen is produced and stored in the liver cells and hydrated muscles with the four parts of water. It is the secondary long-term energy storage. Muscle glycogen can be quickly converted into glucose by muscle cells and liver glycogen converts into glucose for use throughout the body including the central nervous system. 


Structure of Glycogen

Glycogen is built with long polymer chains of glucose units bonded with alpha acetal linkage. This acetal linkage is formed by combining the carbonyl group and the alcoholic group. If the carbonyl group is an aldehyde group i.e (-CHO) and also known as hemiacetal if there is a ketonic group. If 2 alkoxy groups are bonded to the same carbon atom, it belongs to the acetal group.


Glycogen is the analog of starch i.e., glucose polymer, in plants, it acts as energy storage. It has the same structure as amylopectin which is a starch, more widely branched and compacted than starch. This polymer of glucose residues is linked by a -(1,4) and a-(1,6)- glycosidic bonds. It is found in different cell types in the form of granules in the cytoplasm and plays a vital role in the glucose cycle. It is an energy reserve that is easily mobilized to meet the needs for glucose.


Every glycogen granule has its core in protein as the glycogen is synthesized. Glycogen is stored in the hydrated form In muscles, liver, and fat cells.


Functions of Glycogen

Liver glycogen acts as a reserve to store glucose released by the hepatocyte when there is a necessity to maintain normal blood sugar levels. There is about  40 kcal in body fluids while after a fasting night hepatic glycogen can provide about 600 kcal.


In skeletal and cardiac muscles, glucose from glycogen reserves remains within the cells and can be used as an energy source from muscle work.


The brain consists of a small quantity of glycogen in astrocytes. It gets produced during sleep and can be mobilized upon walking. Glycogen reserves also guarantee a moderate level of protection against hypoglycemia.


It has a specific role in fetal lung type II pulmonary cells. These cells start to produce glycogen at about 26 weeks of gestation and can synthesize pulmonary surfactant.


Other Tissues

Glycogen can also be found in smaller amounts in other tissues like kidney, white blood cells, and red blood cells and in addition to the muscle and liver cells. In order to provide the energy needs of the embryo, the glycogen will be used to store the glucose in the uterus. The glycogen after the breakdown will enter the glycolytic or pentose phosphate pathway or it will be released into the bloodstream. 


Bacteria and Fungi

Microorganisms like bacteria and fungi possess some mechanisms for storing the energy to deal with the limited environmental resources; here the glycogen represents the main source for the storage of energy. The nutrient limitations such as low levels of phosphorus, carbon, sulfur or nitrogen can stimulate the glycogen formation in yeast. 


The bacteria synthesize glycogen in response to the readily available carbon energy sources with restriction of other required nutrients. The yeast sporulation and bacterial growth are associated with glycogen accumulation. 


Metabolism of Glycogen

The glycogen homeostasis which is a highly regulated process will allow the body to release or store the glucose depending upon its energetic needs. The steps involved in glycogen metabolism are glycogenesis or glycogen synthesis and glycogenolysis or glycogen breakdown.


Glycogenesis or Glycogen Synthesis

The glycogenesis requires energy that is supplied by Uridine Triphosphate (UTP). glucokinase or hexokinase first phosphorylate the free glucose to form glucose-6 phosphate which will be then converted to glucose-1 phosphate by the phosphoglucomutase. The UTP glucose-1 phosphate catalyzes the activation of glucose in which the glucose-1 phosphate and UTP react to form UDP glucose.


The protein, glycogen catalyzes the attachment of UDP glucose, itself in the glycogen synthesis. Glycogenin contains a tyrosine residue in each subunit that will serve as an attachment point for the glucose; further glucose molecules will be then added to the reducing end of the previous glucose molecule in order to form a chain of nearly eight glucose molecules. By adding glucose through α-1, 4 glycosidic linkages the glycogen synthase then extends.


The branching catalyzed by amyloid 1- 4 to 1- 6 transglucosidase is called the glycogen branching enzyme. A fragment of 6- 7 glucose molecules gets transferred from the glycogen branching enzyme from the end of a chain to the C6 of a glucose molecule that is situated further inside of the glucose molecule and forms α-1, 6 glycosidic linkages.


Glycogenolysis or Glycogen Breakdown

The glucose will be detached from glycogen through the glycogen phosphorylase which will eliminate one molecule of glucose from the non-reducing end by yielding glucose-1 phosphate. The glycogen breakdown that generates glucose- 1 phosphate is converted to glucose- 6 phosphates and this is the process that requires the enzyme phosphoglucomutase.


Phosphoglucomutase will transfer a phosphate group from a phosphorylated serine residue within the active site to C₆ of glucose- 1 phosphate and it will be attached to the serine within the phosphoglucomutase and then the glucose- 6 phosphates will be released. 


Glycogen phosphorylase will not be able to cut glucose from branch points, so the debranching will require 1- 6 glucosidase, glycogen debranching enzyme (GDE) or 4- αglucanotransferase which will have glucosidase activities and glucosyltransferase. 


Nearly four residues from a branch point, the glycogen phosphorylase will be unable to remove the glucose residues.


The GDE will cut the final three residues of the branch and it will attach them to C₄ of a glucose molecule at the end of another branch and then eliminate the final α- 1- 6 linked glucose deposit from the branch point.


Glycogen and Diet

The food is taken, and the activities done can influence the production of glycogen and the way the body will function. With a low- carb diet, the primary source for glucose synthesis i.e. the carbohydrate will be suddenly restricted.


During the start of a low- carb diet, the glycogen stores will be severely depleted which will result in symptoms of mental dullness and fatigue. Then when the body starts to adjust and renew its glycogen stored then the body will return to the normal stage. Any weight loss effort can trigger this effect to some extent.


At the starting of a low- carb diet, the body will experience a huge drop in weight which will plateau and may even increase after a period of time. This is mainly because of the glycogen which will be composed mainly of water that will be 3- 4 times the weight of glucose itself.


The rapid depletion of glycogen at the beginning of the diet will trigger the rapid loss of water weight. Then, when the glycogen stores are renewed, the water weight returns causing weight loss to halt. It is necessary to keep in mind that this is caused by the temporary gain in water weight and not the fat and the fat loss can continue in spite of this short-term plateau effect.


During exercise, the body undergoes glycogen depletion and most of the glycogen will be depleted from the muscle. So while doing exercise, the person can use carbohydrate loading which means the consumption of large amounts of carbohydrates in order to increase the capacity for the storage of glycogen. Glycogen is different from the hormone glucagon and it also plays an important role in carbohydrate metabolism and blood glucose control. 

FAQs on Glycogen

1. What is glycogen and what is its primary function in animals?

Glycogen is a large, branched polysaccharide that serves as the main form of glucose storage in animals and fungi. Its primary function is to act as an energy reserve. When the body has excess glucose, it converts it into glycogen for storage; when energy is needed, it breaks down glycogen to release glucose into the bloodstream.

2. What is the chemical structure of glycogen?

The structure of glycogen is a highly branched polymer of glucose units. The glucose molecules in the main chain are linked by α-1,4 glycosidic bonds. Branch points are created by α-1,6 glycosidic bonds, which occur approximately every 8 to 12 glucose residues. This extensive branching makes the molecule compact and allows for rapid synthesis and breakdown.

3. What are the main building blocks of a glycogen molecule?

The main building block, or monomer, of a glycogen molecule is glucose. Thousands of glucose units are linked together through glycosidic bonds to form the large polysaccharide structure of glycogen, making it an efficient way to store sugar in the body.

4. Where is glycogen stored in the human body and in which part of the cell?

Glycogen is primarily stored in two main locations in the human body:

  • The Liver: Liver glycogen is used to maintain normal blood glucose levels throughout the body.
  • Skeletal Muscles: Muscle glycogen serves as a direct, local source of energy for muscle contraction during exercise.
Within the cells, glycogen is found as granules in the cytoplasm.

5. How is the structure of glycogen different from starch, and why is this structural difference functionally important?

Both glycogen and starch are polymers of glucose, but they differ in their branching structure. Glycogen is more highly branched and compact than amylopectin, the branched component of starch. This high degree of branching in glycogen provides many non-reducing ends from which glucose units can be rapidly cleaved. This is functionally important because it allows for a much quicker release of glucose to meet the sudden energy demands of animal tissues, such as during exercise.

6. What are the two main processes involved in glycogen metabolism?

Glycogen metabolism is controlled by two opposing processes:

  • Glycogenesis: This is the synthesis of glycogen from glucose. It occurs when blood glucose levels are high, typically after a meal, to store excess energy.
  • Glycogenolysis: This is the breakdown of glycogen into glucose. It is activated when the body needs energy and blood glucose levels are low.
These processes ensure a stable supply of glucose for the body's energy needs.

7. Is glycogen a type of sugar or fat?

Glycogen is a type of complex carbohydrate, not a fat. Specifically, it is a polysaccharide, which means it is a large molecule made of many smaller, repeating sugar units (glucose) linked together. Fats, or lipids, are a completely different class of organic molecules with a distinct chemical structure and are used for long-term energy storage.

8. Why can't the brain use the glycogen stored in muscles for its energy needs?

Muscle cells lack a key enzyme called glucose-6-phosphatase. This enzyme is necessary to release free glucose from the cell into the bloodstream. Since muscle cells cannot release their stored glucose, muscle glycogen can only be used as a local energy source for the muscles themselves. The liver, which does have this enzyme, is responsible for breaking down its glycogen stores to supply glucose to the brain and other organs via the bloodstream.

9. How does glycogen differ from the hormone glucagon?

Glycogen and glucagon are often confused but have very different roles.

  • Glycogen is a storage molecule. It is a large polysaccharide made of glucose that sits inside liver and muscle cells as an energy reserve.
  • Glucagon is a hormone. It is a protein that acts as a chemical messenger, signalling the liver to break down glycogen (glycogenolysis) when blood sugar levels are low.
  • In short, glucagon acts on glycogen to regulate energy.

10. What are some diseases caused by abnormal glycogen metabolism?

The most common disease involving glycogen metabolism is diabetes mellitus, where abnormal insulin levels can lead to either excessive accumulation or depletion of liver glycogen. Additionally, there is a group of rare genetic conditions known as Glycogen Storage Diseases (GSDs). These are caused by deficiencies in the specific enzymes required for glycogen synthesis or breakdown, leading to the buildup of abnormal forms or amounts of glycogen in tissues.