Glycogen Metabolism
Dr. Atirah Tauseef
1. Introduction to Glycogen and its physiological importance
Glycogen is the storage polysaccharide of animals. It is present in all cells, but it is most prevalent in the
liver and the muscles. Glycogen consists of glucose molecules linked together with (1⭢4) linkages with
(1⭢6) branch points occurring every 8 to 12 residues. The purpose of the high branched structure is to
have many nonreducing ends so that glucose can be rapidly mobilized in times of metabolic needs.
The nonreducing ends are shown in red. The residue that starts a branch is shown in green.
Glycogen metabolism is important for several reasons.
Glycogen stores in the liver are used to maintain a constant blood
glucose concentration. Muscles also maintain glycogen stores as a
reservoir of glucose for strenuous muscular activity.
The synthesis and degradation of glycogen occur by different metabolic
pathways allowing for reciprocal regulation.
In addition, the enzymes of glycogen metabolism are under hormonal
regulation.
Glycogen Degradation (Glycogenolysis)
The biochemical pioneers of glycogen metabolism were the Cori’s, Carl and
Gerty, a husband-and-wife team. They demonstrated the glycogen is broken
down by phosphorolysis.
Glycogenn + Pi Glucose-1-phosphate + glycogenn-1
Glycogen phosphorylase catalyzes this reaction. This enzyme catalyzes the sequential phosphorolysis of
glucose residues from a nonreducing end. The bond between the C1 carbon atom and the glycosidic
oxygen atom is cleaved by inorganic phosphate in such a way that the stereochemistry at the C1 carbon is
maintained.
, CH2OH CH2OH
O H H O H
Advantages of Phosphorylis
H
H H
OH H OH H
OH O O R This phosphorolytic cleavage is
H OH H OH
advantageous because the cell is saved
the expense of phosphorylating
glucose with ATP.
Glycogen
Phosphorylase In addition, the phosphorylated
glucose cannot diffuse out of the cell.
CH2OH CH2OH
H O H
H
The retention of configuration at the
OH H stereocenter is an important clue into the
HO O R mechanism of this enzyme. Sn2 substitution
reactions proceed with inversion of
configuration at the stereocenter. Retention
implies a Sn1 like substitution mechanism.
H O H Sn1 mechanism begins with the dissociation
H
OH H + of the leaving group to form a carbocation.
O
OH
O P O-
H OH
H OH
O-
Glycogen phosphorylase requires a pyridoxl-5’-phosphate cofactor. This
cofactor is covalently bound to a lysine residue via a Schiff base. Crystal
structures show that the inorganic phosphate molecule lies between the
pyridoxal-5’-phosphate and the glycogen substrate. It appears that the 5’-
phosphate of pyridoxal phosphate functions as a general acid/base during
catalysis. The inorganic phosphate donates its hydrogen to the glycogen n-1
residue to form a resonance stabilized oxonium ion. The oxonium ion is
attacted by the phosphate to form a-glucose-1-phosphate. One important
aspect of this enzyme is that water is completely excluded from the active site.
CH2OH CH2OH
OH
O CH
2
H2 OH
-
O P O C
O-
N
H CH3
H
O
Pyridoxine
Viatamin B6
O
PLP CH2OH
O
H O H
H
OH H O CH
H2
O R - OH
OH O P O C
H OH
O-
CH2OH CH2OH
H O O N
H H H H H CH3
OH H H H
OH
OH O OH
-
H OH H OH
O
- -
O P O O
H
Dr. Atirah Tauseef
1. Introduction to Glycogen and its physiological importance
Glycogen is the storage polysaccharide of animals. It is present in all cells, but it is most prevalent in the
liver and the muscles. Glycogen consists of glucose molecules linked together with (1⭢4) linkages with
(1⭢6) branch points occurring every 8 to 12 residues. The purpose of the high branched structure is to
have many nonreducing ends so that glucose can be rapidly mobilized in times of metabolic needs.
The nonreducing ends are shown in red. The residue that starts a branch is shown in green.
Glycogen metabolism is important for several reasons.
Glycogen stores in the liver are used to maintain a constant blood
glucose concentration. Muscles also maintain glycogen stores as a
reservoir of glucose for strenuous muscular activity.
The synthesis and degradation of glycogen occur by different metabolic
pathways allowing for reciprocal regulation.
In addition, the enzymes of glycogen metabolism are under hormonal
regulation.
Glycogen Degradation (Glycogenolysis)
The biochemical pioneers of glycogen metabolism were the Cori’s, Carl and
Gerty, a husband-and-wife team. They demonstrated the glycogen is broken
down by phosphorolysis.
Glycogenn + Pi Glucose-1-phosphate + glycogenn-1
Glycogen phosphorylase catalyzes this reaction. This enzyme catalyzes the sequential phosphorolysis of
glucose residues from a nonreducing end. The bond between the C1 carbon atom and the glycosidic
oxygen atom is cleaved by inorganic phosphate in such a way that the stereochemistry at the C1 carbon is
maintained.
, CH2OH CH2OH
O H H O H
Advantages of Phosphorylis
H
H H
OH H OH H
OH O O R This phosphorolytic cleavage is
H OH H OH
advantageous because the cell is saved
the expense of phosphorylating
glucose with ATP.
Glycogen
Phosphorylase In addition, the phosphorylated
glucose cannot diffuse out of the cell.
CH2OH CH2OH
H O H
H
The retention of configuration at the
OH H stereocenter is an important clue into the
HO O R mechanism of this enzyme. Sn2 substitution
reactions proceed with inversion of
configuration at the stereocenter. Retention
implies a Sn1 like substitution mechanism.
H O H Sn1 mechanism begins with the dissociation
H
OH H + of the leaving group to form a carbocation.
O
OH
O P O-
H OH
H OH
O-
Glycogen phosphorylase requires a pyridoxl-5’-phosphate cofactor. This
cofactor is covalently bound to a lysine residue via a Schiff base. Crystal
structures show that the inorganic phosphate molecule lies between the
pyridoxal-5’-phosphate and the glycogen substrate. It appears that the 5’-
phosphate of pyridoxal phosphate functions as a general acid/base during
catalysis. The inorganic phosphate donates its hydrogen to the glycogen n-1
residue to form a resonance stabilized oxonium ion. The oxonium ion is
attacted by the phosphate to form a-glucose-1-phosphate. One important
aspect of this enzyme is that water is completely excluded from the active site.
CH2OH CH2OH
OH
O CH
2
H2 OH
-
O P O C
O-
N
H CH3
H
O
Pyridoxine
Viatamin B6
O
PLP CH2OH
O
H O H
H
OH H O CH
H2
O R - OH
OH O P O C
H OH
O-
CH2OH CH2OH
H O O N
H H H H H CH3
OH H H H
OH
OH O OH
-
H OH H OH
O
- -
O P O O
H
