Download Glycogen Metabolism

Glycogen Metabolism
Dr. Sooad Al-Daihan
Biochemistry department
Glycogen
Glycogen is a homopolysaccharide of D-glucose residues linked by: 
α(14) glycosidic bonds, mainly 
α(16) glycosidic bonds, at branch points. 
Each branch is made of 6‐12 glucose units 
Glucose is stored as glycogen predominantly in liver and muscle cells. 
Function of Glycogen:
Liver glycogen: 
It maintains normal blood glucose concentration especially •
during the early stage of fast (between meals).
After 12‐18 hours fasting, liver glycogen is depleted. •
Muscle glycogen: 
It acts as a source of energy within the muscle itself especially •
during muscle contractions.
Muscle glycogen is depleted after prolonged exercise. •
Glycogenesis:
Glycogenesis is the formation of glycogen in liver and muscles 
It occurs in the cytosol 
Blood glucose
Substrates for
In liver
Other hexoses: fructose &
galactose
glycogen
synthesis:
Non carbohydrate sources:
glycerol & lactategluconeogenesis
glucose, then to glycogen
In muscles
Blood glucose
ONLY
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Uridine diphosphate glucose (UDP‐glucose) is the immediate 
precursor for glycogen synthesis
UDP‐glucose is formed from glucose‐1‐phosphate: 
O
UDP-Glucose Pyrophosphorylase
CH2OH
HN
O
H
H
OH
H
O
H
H
O
P
O
OH
O
O
OH

+
O

O
P
O
P
O
O
O
CH2
N
O
H
H
OH
H
OH
H
O
CH2OH
HN
O
H
O
H
O
OH
H
O
UTP
PPi
H
OH
P
O
glucose-1-phosphate
H
O
O
OH
P
O
O
O
O

UDP-glucose
P
O
O
CH2

N
O
H
H
OH
H
OH
H
Cleavage of PPi is the only energy cost for glycogen synthesis 
(one ~P bond per glucose residue)
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Glycogenin is an enzyme that initiates 
glycogen synthesis by catalyzing the attachment
of a glucose molecule to one of its own
tyrosine residues.
UDP is released as a product 
Glycogenin then catalyzes glucosylation at 
C4 of the attached glucose (UDP‐glucose again
the donor), to yield an O‐linked disaccharide
with α(14) glycosidic linkage
This is repeated until a short linear glucose 
polymer (glycogen primer) with α(14)
glycosidic linkages is built up on Glycogenin.
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Glycogen Synthase then catalyzes elongation 
of glycogen chains initiated by Glycogenin by
transfering the glucose moiety of UDP-glucose to
the hydroxyl at C4 of the terminal residue of a
glycogen chain to form an a(14) glycosidic
linkage branches up to 11 glucose units.
A branching enzyme transfers a segment 
(minimum 6 Glc residues) from the end of a
glycogen chain to the C6 hydroxyl of a glucose
residue of glycogen to yield a branch with an
α(16) linkage. The new branches are elongated
by the glycogen synthase and the process is
repeated.
Glycogenolysis:
Glycogenolysis is the breakdown of glycogen into glucose (in liver) 
and lactic acid (in muscles).
It occurs in the cytosol. 
Two major enzymes participate in all glycogen 
degradation:
Glycogen phosphorylase 
Glycogen de-branching enzyme  has 2 independent active 
sites, consisting of residues in different segments of a single
polypeptide chain:
Transferase •
α (16) glucosidase •
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Glycogen Phosphorylase (the key enzyme of
glycogenolysis) catalyzes phosphorolytic cleavage
(addition of Pi) of the α(14) glycosidic
linkages
of
glycogen,
releasing
glucose‐1‐phosphate as reaction product
Always acts at nonreducing end, stops at
fourth glucose from α (16) branch point
The transferase transfers 3 glucose residues
from a 4-residue limit branch to the end of
another branch, diminishing the limit branch to
a single glucose residue .
The α(16) glucosidase then catalyzes
hydrolysis of the α(16) linkage by adding
H2O, yielding free glucose




The major product of glycogen breakdown is 
glucose‐1‐phosphate, from Phosphorylase
activity.
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Glucose‐1‐P formed by phosphorolytic cleavage of 
glycogen is converted into glucose‐6‐P by
Phosphoglucomutase
Glucose 6‐phosphate derived from glycogen can be: 
Used as a fuel for anaerobic or aerobic 
metabolism as in, for instance, muscle;
Converted into free glucose in the liver and 
subsequently released into the blood to
maintain a relatively level of blood glucose;
Processed by the pentose phosphate pathway to 
generate NADPH or ribose in a variety of
tissues
Regulation of Glycogen Metabolism
Glycogen synthase and
glycogen phosphorylase
are the targets of:
Allosteric modulators
Covalent reversible
modification
(phosphorylation)
The actions of the hormones
epinephrine, glucagon,
and insulin on both
enzymes are indirect
Regulation by Covalent Modification
Glucagon:
-Low levels of glucose induce
release of glucagon
-Acts primarily on liver cells.
Epinephrine:
- Low levels of glucose induce
release of Epinephrine
- Acts primarily on skeletal
muscle.
Insulin:
-High levels of glucose induce
release of insulin from β‐ cells of islets
of Langerhan in the pancreas.
-Detected by receptors at surface of
muscle and liver cells.
They BOTH Stimulates glycogen
breakdown & inhibits
glycogenesis.
Stimulates glycogenesis &
inhibits glycogenolysis
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Red=Inactive
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Red=Inactive