How to Break Down Glycogen Fast

Biochemistry for Medicines: The Glycogen Metabolism

Table of Contents


Image: “Regulation of glycogen metabolism (glycogen synthesis)” by Yikrazuul. License: CC BY-SA 3.0


Glycogen: storage form of glucose

Significance and localization of glycogen

The most important nutritional components of humans are carbohydrates. Carbohydrates are fuels, synthesis precursors of lipids, amino acids and energy stores in the form of Glycogen.

The glycogen of the human and animal organism is comparable to the starch in plants. Due to a special chemical structure is a quick assembly and dismantling possibleso that the body can react quickly to a possible lack of glucose.

Glycogen is formed in the cells cytosolic granules saved. These glycogen granules contain both the enzymes for building up and breaking down. Glycogen is present in all body cells - except in erythrocytes. The quantities for personal use in each cell are minimal.

Significant amounts of glycogen are only stored in two organs: the liver (approx. 150 g) and the skeletal muscles (approx. 300 g).

Function of glycogen stores

The Function of glycogen stores the two storage locations liver and skeletal muscles are different:

  • The Liver glycogen serves to maintain the blood glucose concentration. So it is responsible for the whole organism, especially for the brain and the erythrocytes.
  • The Skeletal muscle glycogen is used exclusively for the muscles' own needs.

Structure of the glycogen

Glycogen is made up of glucose units, which alpha-1-4 O-glycosidic and at branch pointsalpha-1-4 O-glycosidic are linked.

These links lead to a tree-like structure with up to 50,000 glucose monomers, which are visible as grains in the cytosol with the electron microscope. Glycogen provides energy storage without osmotic side effects, since it is only minimally active osmotically due to its very small size. Free glucose could not be stored due to the high osmotic activity.

Note: Free glucose would burst any cell due to osmotic activity.

Another advantage is the wide branching of the glycogen. The resulting numerous terminal molecules ensure rapid mobilization and constant maintenance of the glucose level in the blood.

Glycogen synthesis

A glycogen synthesis usually does not consist of the formation of new glycogen but of an addition to existing glycogen molecules. Each of these molecules possesses in the core Glycogeninwhich is a glycoprotein and which remains as a residue when glycogen is completely broken down.

Figure 3 provides an overview of the most important glycogen synthesis reactions.

Step 1 of glycogen synthesis

The first step corresponds to the first reaction of glycolysis. Glucose becomes too Glucose-6-phosphate phosphorylated. In the skeletal muscles, this reaction is catalyzed by the Hexokinase. It's in the liver Glucokinase active.

Step 2 of glycogen synthesis

An isomerization follows Glucose-1-phosphate through the Phosphoglucomutase.

Step 3 of glycogen synthesis

In order to produce an O-glycosidic compound for the synthesis of glycogen, a high level of energy is necessary. For this reason, glucose-1-phosphate is first produced by a reaction with UTP (Uridine triphosphate) activated. This creates UDP glucose and Pyrophosphate, which follows directly from the Pyrophosphatase is hydrolytically split into two phosphates.

Step 4 of glycogen synthesis

Now the glucose can reach the OH group of the C4 a non-reducing end of the glycogen. With this through the Glycogen synthase catalyzed reaction, UDP is released, which is triggered by a phosphorylation reaction ATP dependent can be regenerated to UTP.

New synthesis of a glycogen molecule

New glucose molecules can only attach to an existing glycogen molecule if the unbranched chain of an existing glycogen molecule is at least four glucose units long. For the new formation is a Primer (Starter molecule) essential. In this case, the protein works as a primer Glycogenin with its activity as a glycosyl transferase.

The Glycosyl transferase links one Tyrosyl residue of the protein with the UDP-glucose - UDP is split off and glucose molecules are attached. If eight glucose units are attached to the tyrosyl residue of glycogenin, the glycogen synthase can lengthen them.

Incorporation of branch points in the glycogen

There is a separate enzyme for the branching points, which follows a very specific pattern in its work: The branching enzyme = branching enzymes.

The Amylo-1,4 - 1,6-transglucosylase (branching enzyme) binds to a linear alpha-1-4 chain for the synthesis of an alpha-1-6 branching point, which consists of at least eleven glucose monomers. There will be seven Glucose monomers detached as a chain and transferred to the OH group of the C6 of a glucose residue. Thus there are at least four glucose monomers between two branch points.

Notice: Due to the high degree of branching of the glycogen, there is a large number of non-reducing ends at which the glycogen can build up and break down. This makes it possible to quickly access the glycogen store in order to lower or increase the blood glucose level if necessary.

The breakdown of glycogen: Glycogenolysis

The Glycogenolysis takes place in a different way than glycogen build-up. A high-energy connection is delivered directly: Glucose-1-phosphate. It works as follows:

  • The cleaves at the free, non-reducing ends of the glycogen Glycogen phosphorylase Glucose-1-phosphate phosphorolytically from glycogen. Free inorganic phosphate is required for this. Glucose-1-phosphate can isomerize to glucose-6-phosphate and is used for glycolysis.
  • The liver owns the Glucose-6-phosphatasewhereby it is able to convert glucose-6-phosphate to glucose, which is used to maintain blood glucose levels. The skeletal muscles do not have this enzyme and therefore cannot release glucose into the blood.
  • The glycogen phosphorylase is Pyridoxal phosphate (PALP) dependent and can only cleave alpha-1-4 O-glycosidically linked glucose monomers. It terminates the phosphorolytic cleavage process four glucose monomers before an alpha-1-6 branching point.

Degradation of the branches in the glycogenolysis

The Debranching enzyme (4-alpha-glucanotransferase) is a bifunctional enzyme that is responsible for breaking down these branching points. It has the following functions:

  • Transferase activity: Separation of 3 of the 4 remaining glucose monomers before branching and transferring these to a free non-reducing end of the glycogen.
  • Glucosidase activity: The alpha-1-6 branching point is cleaved by hydrolysis, producing glucose.

Image: “Structure of glycogen. Points of attack of some enzymes marked for build-up and breakdown. " by Ga.rp ~ commonswiki. License: CC BY-SA 3.0

Regulation of glycogen metabolism

The glycogen metabolism is regulated by two enzymes: the Glycogen phosphorylase and the Glycogen synthase. The coordination is primarily dependent on hormone-mediated and partly also allosteric regulatory effects.

The allosteric regulation is a form of regulation of enzyme activity that occurs with certain enzymes (allosteric enzymes), which are almost always composed of several sub-units. These can exist in more than one stable conformation of the overall structure.

A negative feedback leads to an inhibition of the activity or the synthesis of one or more enzymes of a reaction chain by the end product. The inhibition of enzyme synthesis will Enzyme expression called. When the enzyme activity is inhibited, one speaks of an allosteric effect.

Regulation of glycogen breakdown

Two isoforms of glycogen phosphorylase exist in the liver and the skeletal muscles: Since the glycogen metabolism takes place differently in these two parts of the body Muscles and liver regulated separately.

Regulation of glycogen breakdown in skeletal muscle and all non-liver cells

Two forms of glycogen phosphorylase exist in skeletal muscle: The Phosphorylase a (active form) and the Phosphorylase b (inactive form). The conversion from inactive to active form is carried out by the Phosphorylase kinase catalyzed. This enzyme is controlled by hormone signals. The phosphorylase kinase is produced by the enzyme Protein kinase A (PK A) regulated by phosphorylation.

Have another activating effect in the skeletal muscleCalcium ions. When the muscles are working, calcium ions are produced from the sarcoplasmic reticulum released, so the intracellular calcium concentration increases. The actual activation of the glycogen phosphorylase is carried out by a Calcium-calmodulin complex.

The Phosphorylase b is also subject to allosteric influences. The inactive enzyme can become partially active, AMP can activate phosphorylase b. Even before the phosphorylase kinase becomes active when the cell needs energy (hormonally controlled), ATP and glucose-6-phosphate inhibit the activation of phosphorylase b, so the inactive state is favored. This mechanism prevents the unnecessary breakdown of glycogen in the muscle when the energy requirement has already been met.

Regulation of glycogen breakdown in the liver

There are also hepatic phosphorylase a and phosphorylase b, which are converted by the phosphorylase kinase. However, ATP and AMP are not important in the liver because the liver does not break down glycogen for its own use. The liver instead uses fatty acids to meet its own energy needs.

Regulation of glycogen synthesis

The regulation of glycogen synthesis takes place in the same way in the liver and in the skeletal muscles. Glycogen synthase exists in an active dephosphorylated form, the Glycogen synthase a. The inactive phosphorylated form represents the Glycogen synthase b The conversion into the respective forms takes place without the interposition of a further kinase by the protein kinase A.

Here too, glycogen synthase b is subject to allosteric regulation. It is activated by high concentrations of glucose-6-phosphate.

Note: Don't be confused: the glycogen phosphorylase is active in a phosphorylated form - the glycogen synthase in a dephosphorylated form.

Hormonal regulation of glycogen metabolism

The aim of hormonal regulation is to ensure that the synthesis and breakdown of glycogen do not take place at the same time. Three hormones play an important role here: Glucagon, adrenaline and insulin. Glucagon and adrenaline are responsible for increased glycogen breakdown, while insulin causes increased glycogen synthesis.

When the insulin receptor is activated, the Phosphodiesterase activated, resulting in decreased cAMP level leads what the Protein kinase (PKA) is inactivated. An inactive PKA leads to reduced phosphorylation of the phosphorylase kinase, which means that the glycogen phosphorylase is less activated by phosphorylation. This reduces the breakdown of glycogen.

In addition, the protein kinase B is activated, which strengthens the Glycogen Synthase Kinase-3 (GSK3) phosphorylated and thus inactivated. As a result, GSK3 phosphorylates glycogen synthase to a lesser extent, so that it becomes more active, which increases glycogen build-up.

The phosphoprotein phosphatase-1 (PP1) catalyzes the crucial Dephosphorylation of glycogen synthasewhich is responsible for glycogen synthesis. You can through the Downstream mechanism are inactivated by adrenaline and glucagon (cAMP - PKA), so that adrenaline and glucagon contribute to the deactivation of glycogen synthesis.

Note: Adrenaline and glucagon have an antagonistic effect on the signal cascades mentioned, which are activated or deactivated by insulin.

Glycogen metabolism and blood glucose levels

The blood contains very little glucose. The normal level of glucose in the blood is 80-120 mg / 100ml Blood. This corresponds to approx. 1g / l blood, so the blood contains only 5g glucose in relation to the total volume.

The liver is able to register the current blood glucose concentration and to adjust the glycogen metabolism accordingly. If the blood glucose level is too low, glucose is released. When blood glucose levels are high, more glycogen is synthesized. Glucose causes an insulin secretion Activation of glycogen synthase and a Deactivation of glycogen phosphorylase.

If glucose is administered intravenously, the enzymatic activity of glycogen phosphorylase and that of glycogen synthase decrease within a few minutes.

Note: The muscles and other tissues do not have these special regulatory mechanisms. The "waste" of glycogen in hunger states is prevented by controlling the glycogen breakdown via adrenaline.

Clinic digression: glycogen storage diseases

Under Glycogenoses one understands pathological deposits of glycogen in organs and in muscle tissue. Enzyme defects in glycogen metabolism are responsible for this. The most common is the autosomal recessive inherited defect of glucose-6-phosphorylase: the glycogen is still being built up, but can never leave the cell.

The liver stores more and more glycogen, and the result is one Hepatomegaly (up to 10 kg). Furthermore, the glucose level in the blood can no longer be maintained. Serious ones come about Hypoglycemia between the meals.

Up to now eleven types of glycogenosis with further sub-forms have been recorded. In addition to hepatomegaly, typical symptoms and complications include: hypoglycaemia, nephromegaly, liver cirrhosis and muscle weakness.

They are most common forms of glycogenosis:

  • Von Gierke disease (type I)
  • Pompe disease (type II)
  • Cori-Forbes disease (type III)

The main therapeutic aim is to keep the blood glucose level constant in order to avoid severe hypoglycaemia (especially at night).

Popular exam questions about glycogen metabolism

The solutions can be found below the references.

1. Which statement about glycogen metabolism is incorrect?

  1. Glycogen phosphorylase is pyridoxal phosphate (PALP) -dependent.
  2. The debranching enzyme (4-alpha-glucanotransferase) is a bifunctional enzyme.
  3. The liver glycogen is used to maintain the blood glucose concentration.
  4. The glycogen metabolism is regulated by two enzymes: glycogen phosphorylase and glycogen synthase.
  5. The amylo-1,4-1,6-transglucosylase (branching enzyme) binds to a linear alpha-1-4 chain, which consists of at least five glucose monomers, to synthesize an alpha-1-6 branching point.

2. Which statement about glycogen is incorrect?

  1. Glycogen is stored in the form of cytosolic granules.
  2. The molecular structure of the glycogen enables rapid build-up and breakdown.
  3. Glycogen is mainly stored in the liver and smooth muscle cells.
  4. Glycogen has a very low osmotic activity.
  5. Glycogen is the human equivalent of starch in plant organisms.

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Dettmer et al .: Short textbook biochemistry. Elsevier Publishing House. Munich 2013.

Horn et al .: Human Biochemistry. Thieme publishing house. Stuttgart 2012.

Rassow et al .: Dual Series Biochemistry. Thieme publishing house. Stuttgart 2012.

Metabolic regulation via Spektrum.de

Solutions to the exam questions: 1E, 2C

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