Glycogen Metabolism
Prof; Mohamed El-Boshy
Introduction:
Glycogen is the storage form of glucose.
A constant source of blood glucose is required for
human and animal life.
Glucose is derived from glycogen in between
meals.
Location of glycogen: Glycogen is present mainly
in the cytoplasm of liver and muscles.
Liver glycogen is about 120 grams about 6% of
liver weight
Muscle glycogen is about 350 grams about 1% of
total muscle weight.
Function of Glycogen:
Liver glycogen: It maintains normal blood glucose
concentration especially during the early stage of fasting
(between meals) After 12-18 hours fasting, liver glycogen is
depleted and start gluconeogenesis.
Muscle glycogen: It acts as a source of glucose units
for glycolysis It gives energy within the muscle itself
especially during muscle contraction.
Structure of Glycogen:
Glycogen is a branched-chain homopolysaccharide
made of -D-glucose.
The primary glycosidic bond is an 1-4 linkage.
Each branch is made of 6-12 glucose units.
At the branching point the chain is attached by 1-6
linkage.
Synthesis of Glycogen (Glycogenesis)
Definition: It is the formation glycogen in liver and muscle.
Substrates for glycogen synthesis:
In Liver: blood glucose, other hexoses fructose and galactose and
non carbohydrate sources (gluconeogenesis) e.g. lactic acid,
glycerol, lactate. these are converted first to glucose then to
glycogen.
In muscles: Blood glucose only.
Reaction:
Glucose molecules are first activated to uridune diphosphate glucose
(UDP-G). Then these UDP-G molecules are added to a glycogen
primer to form glycogen
Glucose ------ UDP-Glucose + Glycogen primer -------Glycogen.
1- Formation of UDP-Glucose (UDP-G):
Glucokinase
Glucose
ATP Mg++
ADP
phosphoglucomutase
Glucose 6 phosphate
Glucose 1 phosphate
Mg++
UTP
UDP-glucose pyrophosphorlase
PPi
UDP-glucose
Glucose
is converted into glucose 6 phosphate In liver Glucokinase, In muscle
hexokinase.
2- Formation of glycogen:
UDP-glucose reacts with glycogen primer which
few molecules of glucose linked together by 1-4
linkage
A protein called glycogenin UDP-G molecules react
with OH of tyrosine of that protein to initiate
glycogen synthesis.
Glycogen synthesis by the action of glycogen
synthase enzyme, UDP-G molecules are added to
glycogen primer causing elongation of the 1-4
branches up to more than 11 glucose units.
UDP-G
Glycogen primer+
Glycogen synthase
Elongated glycogen primer + UDP
Branching enzyme: It transfers parts of the elongated
chains (5-8 glucose residues) to the next chain forming a
new 1-6 glucosidic bond.
The new branches are elongated by the glycogen
synthase and the process is repeated
Degradation of Glycogen
Glycogenolysis
Definition:
It is the break down of glycogen into glucose in the liver
and lactic acid in muscles.
Reaction:
Glycogen Phosphorylase enzyme acts on 1-4 bonds,
breaking it down by phosphorolysis (breaking down by
addition of inorganic phosphate Pi). So it removes
glucose units in the form of glucose -1-phosphate.
Phosphorylase enzyme acts on the branched
containing more than 4 glucosyl units.
When the branch contain 4 glucose units 3 of
them are transferred to a next branch by
transferase enzyme, leaving the last one.
The last glucose unit that is attached to the
original branched by 1-6 bond is removed by
debranching enzyme by hydrolysis (i.e. breaking
the bond down by addition of H2O).
Glucose 1-phosphate molecules are converted to
glucose-6-phosphate by phosphoglucomutase.
Fate of glucose 6 phosphate it converted in the liver cell
into glucose by glucose-6 -phosphatase.
Or In the muscle where there is no glucose 6
phosphatase, so glucose 6 phosphate enters glycolysis
to give lactate
Regulation of glycogenesis and Glycogenolysis
There is a coordinated regulation of glycogenesis and
glycogenolysis where condition leading to stimulation of
glycogenolysis inhibiting at the same time glycogenesis
and vice versa.
During fasting glycogenolysis is stimulated and
glycogenesis is inhibited this provides blood glucose.
After meal part of the absorbed glucose goes to
circulation to be utilized and the remaining 60% is
converted into glycogen in the liver so after meal
glycogenesis is stimulated and glycogenolysis is
inhibited.
The principle enzymes controlling glycogen metabolism
are glycogen synthase and phosphorylase. These are
regulated as follows:
During Fasting:
Blood glucose level is decreased this stimulates secretion
of epinephrine, norepinephrine and glucagon hormones.
These hormones stimulate adenylate cyclase enzyme
which converts ATP into cyclic AMP (c-AMP).
c-AMP stimulates protein kinase enzyme.
Protein kinase enzyme causing phosphorylation of both
glycogen synthase (inactive) and glycogen phosphorylase
(active).
Glycogen synthase
protein kinase
phosphorylated glycogen synthase
ATP
Phosphorylase
ADP
protein kinase
ATP
(In active)
phosphorylated phosphorylase
ADP
(Active)
As a result glycogenolysis will proceed causing
increase of blood glucose
At the same time glycogenesis will be inhibited.
Epinephrine and norepinephrine stimulate mobilization
of calcium ions (Ca 2+) from mitochondria to cytosol.
Ca 2+ ions then combine with a protein called
calmodulin causing conformation changes in it and
activating it.
The active calmodulin causes:
Phosphorylation of both glycogen phosphorlyase
(active) and glycogen synthase (like protein kinase).
This leads to stimulation of glycogenolysis.
it also lead to muscle contraction.
After meal:
Blood glucose level tends to be increased. This stimulates
secretion of insulin hormone.
Insulin causes the following
Stimulation of phosphdiesterase enzyme which converts
cAMP into AMP i.e. abolishes the stimulatory effect of cAMP.
Stimulation of phosphatase enzymes which remove
phosphate from phosphorylase (inhibiting it) and glycogen
synthase (stimulating it). As a result glycogenesis will proceed
and glycogenolysis will be inhibited.
Phosphorylated phosphorylase
Phosphatase
Pi
Phosphorylated glycogen synthase
Phosphatase
Pi
Phosphorylase
(In active)
Glycogen synthase
(Active)
Liver glycogen
Muscle glycogen
Sources
Blood glucose glycogenolysis,
other hexoses as fructose and
galactose and non carbohydrate
sources lactate.
Blood glucose only
Amount
120 gram maximum
400 gram maximum
Concentration
6%
1%
Function
General store of glucose for all
body cells.
Private source of energy
for muscle only
End product
Glucose
Lactate
Effect of insulin
Stimulation of glycogenesis
The Same
Effect of
epinephrine
Stimulation of glycogenolysis
The Same
Effect of Glucagon
Stimulation of glycogenolysis
No effect
Carbohydrate
Depletion
Glycogen runs out
Occurs with:
Starvation
(high
No protein/low
carbohydrates
carb diet)
in diet
(diabetic)
No insulin
