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03b Glycogen Metabolism

03b Glycogen Metabolism

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0% found this document useful (0 votes)
16 views22 pages

03b Glycogen Metabolism

03b Glycogen Metabolism

Uploaded by

curtisandrea242
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Glycogen metabolism

Glycogen metabolism
 Excess glucose is converted to a polymeric form known as glycogen in
vertebrate and starch in plants.
 Glycogen is stored in large granules in the cytosol.

 Glycogen storage occurs mainly in


 Muscles:
− For energy in either aerobic or anaerobic conditions.
− Can be depleted in <1 hour
 Liver
− Maintain blood glucose levels
− Only adequate for 12 to 24 hours

 Glycogen metabolism is generally the same in both liver and muscles.


 Nevertheless, subtle difference do exist in liver and muscles.
Glycogen structure
REMINDER: Monosaccharide have Reducing and Non-reducing End
Glycogen metabolism
Glycogenesis
Hexokinase (muscles)
 Refers to glycogen synthesis for Glucokinase (liver)

storage of excess glucose.

 Step 1
 Formation of UDP-glucose.

 Act as the immediate glucose


donor or substrate for glycogen
synthesis

UDP: uridine diphosphate


Glycogenesis
Step 2 : Addition of glucose to a non-reducing end of a pre-existing glycogen branch (with <4
glucose residues)

Pre-existing glycogen

 An incoming glucose residue(s) bind to the non-reducing (C-4) of the terminal glucose

residue of pre-existing glycogen via its anormeric carbon (C-1).

 As a result, α -1, 4 glyosidic bond is formed.


Glycogenesis
Step 2 : Addition of glucose to a non-reducing end of a pre-existing glycogen branch (with <4
glucose residues)

Pre-existing glycogen branch

Pre-existing glycogen
Glycogenesis
Step 3 : Branching of glycogen: for
Involves transfer of a chain containing 6 to 7 glucose residues from the non-reducing
end of a glycogen branch with ≥11 glucose residues to hydroxyl group at C-6 of an
interior glucose residue

NB: Branching continues to increase glycogen solubility and provide more non-reducing ends for
addition of glucose molecules.
Glycogenesis

What happens when there is NO


pre-existing glycogen for glucose
to be added onto it?

Glycogen synthase CAN NOT


initiate glycogen synthesis

Glycogen synthesis is instead


initiated by the transfer of glucose
residue from UDP-glucose to a
protein, glycogenin,

Form a new chain


of 8 glucose
Glycogenolysis
Glycogenolysis (glycogen breakdown)
 Glycogenolysis involve release glucose residues from glycogen for;
1. Production of energy
2. Restoration of blood sugar levels

 Involves three enzymes


1. Glycogen phosphorylase (break α1→4glycosidic bond)
2. Glycogen debranching enzyme (break α1→6 glycosidic bond)
3. Phosphoglucomutase. (convert glucose-1-phosphate to glucose-6-phosphate)
Glycogenolysis (glycogen breakdown)
Step 1: Glycogen breakdown from the non-reducing end by glycogen phosphorylase
(break α1→4 glycosidic bond)

This continues until 4 glucose residues are left in a branch


Glycogenolysis
Step 2: Debranching of glycogen
Debranching enzyme act in a two-step
reaction;
1. Transfer of a three-glucose
residue oligosaccharide of the
branch.

2. Release of glucose residue


bound by α1→6 glycosidic bond
Glycogenolysis
Step 3: Fate of glucose-1-phosphate

P ①
i


Glycolysis
(Muscles)
Regulation of Glycogen metabolism
 Based on addition of a function group onto a key enzyme (allosteric modification)
Regulation of Glycogen metabolism
 Principle behind allosteric regulation/control
A. Allosteric inhibition/negative allosteric regulation

Active enzyme Inhibited enzyme

Distortion of active site renders the active site inaccessible by substrate


and thus, enzyme is allosteric inhibited
Regulation of Glycogen metabolism
 Principle behind allosteric regulation/control
A. Allosteric activation/positive allosteric regulation

Inactive enzyme activated enzyme

Distortion of active site renders the active site accessible by substrate and
thus, enzyme is activated inhibited
Regulation of Glycogen metabolism
 Based on addition of a function group to a key enzyme (allosteric modification)
I. Presence of a functional group activate the enzyme
II. Removal of a function group inactivate the enzyme

Inactivate Activated
enzyme enzyme
Regulation of Glycogen metabolism
Regulation is achieved through
A. The regulation of the activity of two key enzymes:
1. Glycogen phosphorylase (glycogenolysis)
2. Glycogen synthase (glycogenesis)

B. Influence of two hormones over the activity of key enzymes


1. Glucagon: promote glycogen breakdown
− Activate glycogen phosphorylase
− Inhibit glycogen synthase
2. Insulin promote glycogen synthesis
− Activate glycogen synthase
− Inhibit glycogen phosphorylase
NB: These hormones are produced in response to body energy needs/ blood
Regulation of Glycogen metabolism
When blood sugar levels are low (hypoglycemia)
− Glucagon is produced by alpha cells of the pancreas
− In the liver or muscle to glucagon promote glycogen breakdown
Consequence: activate glycogen phosphorylase Inhibit glycogen synthase
Glycoge
n
synthesi
s
inhibited

glycogen Glucose conc ↑


Regulation of Glycogen metabolism
When blood sugar levels are high (hyperglycemia) or back to normal
− Insulin is produced by beta cells of the pancreas
− In the liver or muscle, insulin promotes glycogen synthesis
Consequence: Activate glycogen synthase Glycogen phosphorylase inhibited
Glycogenolysis inhibited

Glycoge
n
synthesi
s
enhance
d

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