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# Glycogen

Living organisms is mainly based on four major classes of bio molecules - carbohydrates, proteins, nucleotides, and lipids which involve in many biochemical reactions and regulate organisms.

Out of these bio molecules, carbohydrates are the most abundant bio molecules and show several roles in living organisms like energy transportation, being structural components and also involved in immune systems, in the blood clotting process etc.

1. These bio molecules are composed of carbon, oxygen and hydrogen with the general formula Cn(H2O)n. They are basically polyhydroxy aldehydes and ketones.
2. Carbohydrates are made up of tens to hundreds to several thousand monosaccharide units and also called as polysaccharides.
3. Common polysaccharides contain glucose as the monosaccharide unit and synthesized by plants, animals, and humans. They mainly act as a reserve food, involve in structural support (cell wall in plant cell and outer skeleton of insects in the form of chitin) and metabolized for energy.
Polysaccharides mainly act as food preservers, in plants food reserve in the form of starch, while in human beings and other animals it stores in the form of glycogen in the liver and muscles.

## What is Glycogen?

Glycogen is a polysaccharide with general formula (C6H10O5)n which acts as a storage form in animals and human being just like starch in plants. It composes 1,700-600,000 units of glucose which is a monosaccharide. It is synthesized stored primarily in the liver and muscle tissue and readily converts to glucose to provide energy during heavy work. It also stored in the cytosol in the form of small granules. Glycogen generally stored with water in 1:3 ratio.

• The structural units of glycogen are very similar to amylopectin with alpha acetal linkages but have more branching and more glucose units.
• Compare to fat, glycogen can be can be rapidly mobilized in skeletal muscle and utilized as fuel substrate in the absence of oxygen, while oxidation of fat requires some amount of energy.
• Fatty acids required oxygen to provide energy while glucose can provide energy in the absence of oxygen and supply energy for anaerobic activity.
• Glycogen regulates the blood glucose levels and stores significantly more limited than adipose tissue. Glycogen mainly synthesized in plants through photosynthesis process with starch and is taken by animals and human as vegetables and other plant materials and products.
• Starch is broken ultimately into the various mono saccharides during digestion which is hydrolysis process and form glucose.

The glucose which is not used immediately is stored in the form of glycogen in the liver and muscles by the process of glycogenesis. Some tissues like liver and skeletal muscle store glucose in a form of glycogen which can be rapidly mobilized. For example, when blood glucose is high, and glycogen is degraded and released glucose into the blood stream, while in case of low blood sugar like fasting muscle uses its glycogen stores for energy and it serves as a buffer to maintain blood-glucose levels.

## Glycogen Structure

Glycogen consists of long polymer chains of glucose units which are bonded by an alpha acetal linkage. An acetal linkage forms by the combination of carbonyl group and alcoholic group. If the carbonyl group is an aldehyde group (-CHO), it termed as hemiacetal and if there is ketonic group, it forms hemiketal bond. If two alkoxy groups are bonded on same carbon atom, it called as acetal group and bond termed as acetal linkage.

In case of glycogen, all alpha-D-glucose bonded to each other by alpha acetal linkage between C1 of one monomer unit and C4 of other monomer unit, hence called as $\alpha$-1,4-glycosidic linkage. Since glycogen is a branched polymer, branching occurs at intervals of 8-10 glucose units. These branches are formed by acetal linkage between C1 and C6

There are possible forms of glycogens, proglycogen which has molecular mass of around 400 kDa and macroglycogen with very high molecular mass. Glycogen can be organized in a globular form in which glucose chains are organized globularly around a core protein of glycogenin with a molecular weight of 38,000. It looks like a branches of tree originated from a center point.

## Glycogen Synthesis

The Glycogen synthesis is called as Glycogenesis and is an endergonic process, hence required some input of energy which provides by UTP (Uridine triphosphate). Glycogenesis is a four steps process in which each step catalyzed by certain enzymes.
1. In first step, glucose is converted into glucose-6-phosphate in the presence of glucokinase or hexokinase enzymes.
2. This glucose-6-phosphate forms glucose-1-phosphate by the action of Phosphoglucomutase.
3. UTP reacts with glucose-1-phosphate to form UDP-glucose and pyrophosphate in the presence of UDP-glucose pyrophosphorylase or Uridyl Transferase.
4. Pyrophosphate further hydrolyzed into 2 molecules of Pi in the presence of pyrophosphatase.
5. The UDP-glucose acts as monomer units progressively lengthens the glycogen chain with (Î±1â†’4) bonded glucose in the presence of enzyme glycogen synthase.
6. This step is needed to initiate by protein glycogenin.

The branching process is catalyzed by branching enzyme (amylo ($\alpha$1-->4) to ($\alpha$1-->6) transglycosylase) which can act upon only a branch having at least 11 residues. It catalyzes the transfer of a terminal fragment of 6-7 glucose residues from a non-reducing end to the C6 hydroxyl group of a glucose residue deeper into the interior of the glycogen molecule.

## Function of Glycogen

1. Glycogen is stored in liver and muscles and acts as storage sites. For all the normal movement and functions, energy is first provided by glucose contained in the bloodstream and after consumption of glucose, energy pulled in the form of glycogen from storage sites.
2. The excess glucose is stored in the form of glycogen in storage sites. After consumption of glucose in various functions for movement, brain power and stores the excess of glucose store in the form of glycogen in the liver and muscles which can be used at a time of need. The synthesis of glycogen from glucose is called as glycogenesis.
3. In case of low blood sugar, a hormone glucagon is released which involves in the conversion of glycogen to blood sugar, a fuel source. This process is known as glycogenolysis.
4. Glycogenolysis process is initiated by glycogen phosporylase or phosphorylase enzyme which involves in cleavage of terminal glycogen residues by inorganic phosphate.
5. This enzyme requires a covalently bound pyridoxal phosphate co-factor (vitamin B6). The cleavage of terminal glycogen residue forms glucose-1-phosphate, which further converted to glucose-6-phosphate by phosphoglucomutase.

Glucose-6-phosphate is used directly for glycolysis in muscle while in liver it decomposed to
glucose during low glucose level. The complete degradation of glycogen requires the action of a second bifunctional enzyme known as debranching enzyme like oligo ($\alpha$-1,4 -->$\alpha$-1,4) glucantransferase. Hence glycogen degradation process completed in three steps.
1. The conversion of glycogen to glucose 1-phosphate
2. Remodeling of the glycogen substrate for further degradation,
3. Formation of glucose-6-phosphate from glucose-1-phosphate for further metabolism.
Two hormones glucagon from the pancreas and epinephrine from the adrenal glands regulate the glycogenolysis process.

Both processes related to glycogen, glycogenesis and glycogenolysis regulated by two enzymes, one involve in glycogen synthesis that is glycogen synthase and another in glycogen degradation that is glycogen phosphorylase.

The action of both enzymes is regulated by circulating hormones including insulin, glucagon and epinephrine and with the level of energy and metabolites available to the cell. The final product of glycogenolysis, glucose 6-phosphate can involve in various pathways.
1. Acts as precursor for glycolysis.
2. Involve in the processing of pentose phosphate pathway to form NADPH and ribose derivatives.
3. During the need of energy, it can be converted into glucose which provide energy during various metabolic processes.

The used glycogen stores as soon as we eat something to prevent the depletion of glycogen level. At the low level of glycogen, body starts the breakdown proteins to use as fuel sources which are harmful for body. The deficiency and abnormal functions of glycogen causes many storage disorders. As the formation and degradation of glycogen involved many enzymes, there are a many around 12 types of glycogen storage disorders where each disorder relates to the lack or malfunction of different enzymes.

For example, the problem associated with the production of those enzymes which involved in glycogen synthesis, it can produce abnormal glycogen units. Similarly the defects with enzymes related to glycogenolysis can lead to the low level of glucose in body that is called as hypoglycaemia, build-up of glycogen in muscles and liver and responsible for the inborn errors of metabolism.

Glycogen storage disorders mainly affect liver and muscles with other parts of the body like the kidney, heart, blood vessels, nervous system and bowel.

Some glycogen storage disorders and associated diseases are as follows.

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