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BiochemistryLecture 7
Glycogen metabolism
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Glycogen
Glycogen is a branched
polymer of glucose.
It has a tree-like
structure; It is a
molecule with one
start and many ends.
The core of glycogen isthe protein
glycogenin.
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Glycogen
Glycogen is themacromolecular storageform of glucose.
This form of energy isreadily available.
Glucose molecules areconnected by -1,4-glycosidic bonds in long
chains. Branches areconnected by -1,6-glycosidic bonds.
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Glycogen
Glucose molecules are connected by -1,4-glycosidic bonds in
long chains. Branches are connected by -1,6-glycosidic
bonds.
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Glycogen balance
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Glycogen balance: Liver
Glycogen is found inmany cells. Largeamounts are stored
in liver (up to 150 g)and muscle cells (upto 300 g).
The glycogen of the
liver serves as aglucose buffer forthe blood glucose.
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Glycogen balance: Muscle
The glycogen of the
muscle serves for its
own energy demand
exclusively.
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Glycogen
meta-bolism
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Glycogen biosynthesis
In liver cells glycogen is either synthesized ordegraded depending on the nutritional status.
Biosynthesis of glycogen begins with the reversible
conversion of glucose 6-phosphate to glucose 1-phosphate.
Step 1: glucose 1-phosphate is converted to uridinediphosphate glucose
(UDP-glucose), a compoundwith a high transfer potential(active glucose)
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Glycogen biosynthesis
Step 2: UDP-glucose is usedto build up glycogen byextending an existing chain.The enzyme glycogensynthase forms -1,4
glycosidic bonds. This is akey enzyme of biosythesisand a point of regulation.
Step 3: Branches will bemade by a branching
enzyme which transfersblocks of about 7 glucoseunits from the end of thegrowing chain.
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Glycogen
meta-bolism
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Glycogen breakdown
Also the breakdown of glycogen requires the
interplay of several enzymes.
The degradation of glycogen always starts at the
ends. Step 4: Phosphorylase catalyzes the phosphorolytic
cleavage of glycogen to release glucose 1-phosphate.
Phosphorylase is the key enzyme of the breakdown
of glycogen.
A special point of this reaction is that glycogen is not
split with water but with phosphoric acid.
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Reaction of glycogen phosphorylase
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Glycogen breakdown
Glucose 1-phosphate is easily isomerized to glucose
6-phosphate, the active form of glucose in the cells,
which can be used for many purposes.
Step 5 and 6: Branch points are degraded by theconcerted action of a glucanotransferase and an -
1,6-glucosidase.
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Glycogen breakdown
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Control of glycogen metabolism
The glycogen metabolism in the liver is controlled by hormones.
Synthesis and breakdown are reciprocally regulated.
Insulin stimulates biosynthesis. Epinephrin (adrenalin) and glucagon stimulate degradation, concomitantly
they also inhibit biosynthesis. Muscle is the primary target of epinephrin,whereas liver is responsive to glucagon.
AMP, the intracellular signal for lack of energy, also stimulatesdegradation.
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Activation of phosphorylase
by hormones
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Activation of phosphorylase by
hormones
The hormones act by binding to their membranereceptors.
A signal transduction cascade transmits and amplifiesthe signal. Details of this cascade are complex and
depend on the cell type. The example shows a need of energy signalled by
epinephrin and glucagon. The final response is thatphosphorylase is converted from an inactive state(phosphorylase b) to an active state (phosphorylase a)
by phosphorylation, which immediately starts thedegradation of glycogen. Eventually, glucose 6-phosphateor glucose is made available.
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Glycogen storage diseases
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Glycogen-storage diseases
Several inherited defects of individual enzymes ofthe glycogen metabolism are known. Collectivelythey are called Glycogen-storage diseases. Theymay cause a variety of different clinical symptoms.
The most common disease is the type I von Gierkedisease, in which glucose 6-phosphatase or atransport system for sugars is absent. Since glucose6-phosphate accumulates in the liver, the
degradation of glycogen is inhibited causing amassive enlargement of the liver, severehypoglycaemia and a few other symptoms.
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Pompe disease
Type II glycogen-
storage disease (Pompedisease)The lysosomes are filled
with glycogen becauseof a deficiency in -1,4-glucosidase, a hydrolyticenzyme confined to
lysosomes. Glycogen inthe cytoplasm isnormal.
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Key words
Glycogen
Glycogenin
-1,4- and -1,6-glycosidic bond
Glycogen balance, biosynthesis and degradation
Glucose 1-phosphate, glucose 6-phosphate
UDP-glucose
Glycogen synthase
Branching enzyme
Phosphorylase a and b
Phosphorolysis hydrolysis
Glucanotransferase
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-1,6-glucosidase
Epinephrine, glucagon, insulin
Signal transduction cascade
Glycogen storage disease Type I von Gierke disease
Type II Pompe disease