Jeddah 1.7 Glycogen

8/3/2019 Jeddah 1.7 Glycogen

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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

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Jeddah 1.7 Glycogen