Glycogen metabolism

Glycogen, is a sugar (carbohydrate) that is raised especially in liver and muscles. Glycogen is composed of a large number of glucose units. In the glycogen metabolism in the need of energy glycogen is broken down and by an excess of energy (glucose) glycogen becomes synthesised. In the glycogen metabolism, the glucose level is held on level in the blood. Glycogen is a fast available energy supply. After glycogen, fats (see fatty acid metabolism) and proteins (see amino acid metabolism) are utilised as an energy supply.
Below you find more (biochemical) information about the carbohydrate glycogen, about the structure and break down of glycogen and the regulation of the glycogen metabolism.

Glycogen
Glycogen break down
Glycogen synthesis
Regulation of glycogen metabolism

Glycogen is a soluble polymer of many glucose units.

Figure: Structure of two outside strands of glycogen. The green glucose unit is the beginning of a new strand. The red glucose units are not the reduced end. The R-groups is the rest of the glycogen molecule. The carbon atoms of glycogen are numbered as 1 to 6, this has been indicated with blue numbers.

In glycogen, glucose is stored as an energy supply. This glycogen is found in the liver and the muscle cells in so-called glycogen granules. In the liver cells the concentrations of glycogen are higher than in muscle cells, but the total quantities of glycogen stored in the muscles is larger than in the liver. This is because all the skeleton muscles together have a much larger mass then only the liver.
The word alpha, in the name of the bonds between the two glucose units, indicates that the two units are in a straight area. The numbers 1.6 and 1.4 mean that the bonds are between the carbon atoms 1 and resp. 4 and 6. By a low energy level (for instance by high effort), glycogen is broken down.
And when sufficient energy (glucose) is present this glucose is stored again as glycogen.


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If energy is needed, the energy supply in the form of glycogen is utilised.
The glycogen is hereby broken down in a way that a glucose-1-phosphate and a glycogen molecule with a glucose unit less arises. This process is called phosphorylyse. This literal means, break down by phosphate.
This break down reaction of glycogen becomes catalysed by phosphorylase (enzyme that catalyses the phosphorylyse).
This enzyme breaks the 1.4 bonds down at the non reduced end of the glycogen molecule.
The enzyme has PLP (pyridoxal 5'phosphate, originating from vitamin B6) necessary as an assistant-factor to let these break downs reaction to take place.

Figure: The breaking (hydrolyse) of the 1.6 bond of the glycogen through the debranching enzyme.

The hereby synthesised glucose must be first phosphorylised till glucose-6-phosphate to become broken down in the glycolysis.
If the 1.6 bond is broken the phosphorylase can go further to break down the 1.4 bonds.



Figure: The phosphorylase can go further again to break the 1.4 bonds.

It is an advantage that glycogen is branched (with the 1.6 bonds), because the phosphorylase enzyme can break the glycogen on more places at the same time. Also glycogen is better soluble as it is more brached.
Through the phosphorylation of glycogen, there are arise a number glucose-1-phosphate molecules.
These molecules can not yet be broken down further in the glycolysis. Firstly, to be able to become broken down, this must be converted into glucose 6-phosphate. This glucose 6-phosphate is possible to be broken down in the glycolysis. This reaction becomes catalysed by phosphoglucomutase.
The active side contain a phosphorylated serine residue. This serine can deliver its phosphate at glucose-1-phosphate, so that glucose-1,6-bisphosphate arises. Then the not phosphorylated serine takes a phosphate group, and there glucose-6-phosphate arises. This can be processed in the glycolysis.


Figure: Transformation of glucose-1-phosphate to glucose-6-phosphate through a mutase.

The formed glucose-6-phosphate can no longer leaf the cell because a phosphate group at is attached.
The livers is an organ that regulates the sugar (glucose) level in your blood. If the muscles work hard the sugar levels go down, because the muscles use many fuel (glucose). The brains work exclusively on glucose.
The liver brings the glucose levels back on level to break first glycogen down and there, as discussed, glucose-6-phosphate is made. This glucose-6-phosphate cannot get out of the cell, it could if the phosphate group gets off.
The liver has an enzyme that can get off this phosphate group. This enzyme, that lies in the "endoplasmatic reticulum" in the cell, is called glucose-6-phosphatease.
This enzyme catalyses the following reaction:

Glucose-6-phosphate + H₂O Glucose + Phosphate

Now the phosphate group off is can the glucose the cell from and in the blood be taken up. The kidneys have, like the liver, also the enzyme glucose- 6-phosphatease. The liver and the kidneys can thus glucose from their cells transports.
Organs as the skeleton muscles and the brains know this enzyme not in their cells, they can glucose thus not from their cells transports. This comes because when these cells glucose in their cell got, they this not gladly more deliver.
These cells use glucose as most important fuel.


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If it sufficient glucose be present becomes this stored in glycogen. Glycogen is composed thus of glucose units.
Firstly for this glucose-1-phosphate at UTP (Uridine Tri Phosphate) is coupled. By this reaction, UDP-Glucose (Uridine Tue Phosphate-glucose) arises and pyrophosphate (PPi). The reaction becomes catalysed through the enzyme UDP-glucose pyrophosphorylase.

Figure: The clutch of glucose-1-phosphate at UTP so that it UDP-glucose and PPi arises.

The formed PPi becomes in the body fast broken until two phosphates, this becomes catalysed by pyrophosphatase:

PPi + H₂O 2Pi

Because this PPi at the same time is broken the balance of the reaction of glucose-1-phosphate and UTP lies strongly to right. So that the reaction can remain lapse good, and it is formed thus good UDP-glucose.

The UDP-glucose can be coupled to a glycogen molecule with at least 4 glucose units.

Because of this the glycogen molecule becomes one glucose unit longer. This reaction becomes catalysed through glycogen synthase.



Figure: The binding of UDP-glucose at a glycogen molecule through glycogen synthase.

By this reaction thus always a beginning of glycogen is necessary with at least 4 units. If in very extreme cases all the glycogen on then has the cell always some other "start briskly". For this "start briskly" is the enzyme glycogenin.
On the manner as until now closed described there only arise alpha 1.4 bonds. Glycogen contain also alpha 1.6 bonds.
This alpha 1.6 bonds arise because an enzyme (the branching enzyme) the alpha 1.4 bonds broken cuts and a new alpha 1.6 bond makes. This puts on after approximately 10 units. The advantage of subdivides glycogen is that the better solubility is and that can become the faster broken.
By the raising of energy (glucose) in glycogen and it later on again break of glycogen goes about 3% energy lost, compared with direct use of glucose. This is a small percentage lose, and this makes one efficient form of energy raise.


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The two different pathways for synthesis and break down of glycogen must be well regulated.
If both pathways would work at the same time there will needlessly many ATP become consumes. If glycogen must be built up or broken is determined by if many or little glucose is present in the organism.
This becomes among other things regulated through hormones as: insulin, epinephrine and glucagon.
The phosphorylase (enzyme that breaks glycogen) in skeleton muscles occur in two forms. An active, phosphorylase a and a not active phosphorylase b. Phosphorylase b becomes converted in phosphorylase a through phosphorylation (a phosphate group to it set) of a serine residue on the phosphorylase b. This reaction becomes catalysed through phosphorylase kinase.



Figure: The convertion of a not active to an active phosphorylase through phosphorylase kinase.

The phosphorylase a can be transformed by hydrolyse of the phosphorylated serine residue again till phosphorylase b.
This reaction becomes catalysed through protein phosphatase 1.
Normal phosphorylase b will always be inactive (there becomes no glycogen broken). In utmost extreme cases, phosphorylase b can become really asset. This lifted then because almost all the energy is finished, then can the cell it no phosphorylase a more make because all the ATP is finished. If there is little energy, there are higher concentrations AMP present in the cell, and lower concentrations ATP and glucose-6-phosphate. Normally there is sufficient ATP and glucose-6-phosphate present so that these compounds hold the phosphorylase b in the inactive form. If these compounds are almost finished and there is many AMP formed, then can the phosphorylase b change so that the well asset becomes (not through phosphorylation only through allosteric modification).
Phosphorylase b (inactive) can become converted in phosphorylase a (asset) under influence of hormones (Epinephrine, Glucagon). Through these hormones, a cascade becomes active.

The hormone epinephrine binds on a particular receptors on muscle cells and glucagon on receptors in liver cells.
At the moment that this hormone binds at the receptor the above cascade active.
Red is inactive and is active is green. Finally thus the inactive phosphorylase b through the phosphorylase kinase becomes converted in active phosphorylase a. The glycogen is broken by phosphorylase a and comes there glucose free. In the liver, the glucose is delivered at the blood, and the sugar rises reflect. In the muscles, there is to be burnt more glucose.
The use of such cascade is that it a large reinforcement acts. Each enzyme can form many substratum (e.g. protein kinase A forms active phosphorylase kinase). And each formed substratum is prevent on its turn an enzyme that again new substratum form can (e.g. phosphorylase kinase forms phosphorylase a). This cascade gives a reinforcement of approximately 1,000,000,000 (10 till the 9e). Hormones come in the blood for in a concentration of approximately 0,000000008 mmol/l, and glucose in approximately 8 mmol/l.
The regulation of glycogen synthesis through hormones gives a partial equal cascade then that for glycogen break down.

Green is again active and red inactive. Glycogen synthase a (active) becomes by the binding of epinephrine converted in glycogen synthase b (inactive). Protein kinase set a phosphate group at the active glycogen synthase a so that the inactive becomes (glycogen synthase b). Through the bond of the hormone thus the break down of glycogen becomes active and the synthesis becomes, through glycogen synthase, stopped. This is because protein kinase A has two substrata namely: Inactive phosphorylase kinase and active glycogen synthase a.
If the sugar levels in the blood went down first the synthesis of glycogen stops and start after that fit defence the break down.
This is because the affinity of the protein kinase A for glycogen synthase a is larger then for the inactive phosphorylase kinase. Firstly glycogen synthase a converted in glycogen synthase b (synthesis stops) becomes. And after that becomes inactive phosphorylase kinase converted in active phosphorylase kinase through which phosphorylase b becomes converted in phosphorylase a (the break down start).

And the other way as the blood sugar level rises firstly the break down is stopped and after that the synthesis is started. This stop of the break down and start by the synthesis becomes in accomplished by the enzyme protein phosphatase 1. This enzyme is made active by the hormone insulin.

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