The Metabolism of Glycogen

in Animals
Polymeric form of storage of glucose -
glycogen
• Glycogen is found primarily in the liver and skeletal muscle; it may
represent up to 10% of the weight of liver and 1% to 2% of the weight
of muscle.
• If this much glucose were dissolved in the cytosol of a hepatocyte, its
concentration would be about 0.4 M, enough to dominate the
osmotic properties of the cell. When stored as a long polymer
(glycogen), however, the same mass of glucose has a concentration of
only 0.01 μM.
Glycogen – a quick source of energy
• The glycogen in muscle is there to provide a quick source of energy for
either aerobic or anaerobic metabolism.
• Muscle glycogen can be exhausted in less than an hour during vigorous
activity.
• Liver glycogen serves as a reservoir of glucose for other tissues when
dietary glucose is not available (between meals or during a fast); this is
especially important for the neurons of the brain.
• Liver glycogen can be depleted in 12 to 24 hours.
• In humans, the total amount of energy stored as glycogen is far less than
the amount stored as fat (triacylglycerol), but fats cannot be converted to
glucose in mammals and cannot be catabolized anaerobically
Glycogenolysis
glycogen phosphorylase
,Debranching enzyme, and
phosphoglucomutase
Glycogen phosphorylase catalyzes
the reaction in which an (14)
glycosidic linkage between two
glucose residues at a nonreducing
end of glycogen undergoes attack
by inorganic phosphate (Pi),
removing the terminal glucose
residue as -D-glucose 1-phosphate
Debranching enzyme, catalyzes two
successive reactions that transfer
branches. Once these branches are
transferred and the glucosyl residue
at C-6 is hydrolyzed, glycogen
phosphorylase activity can
continue.

Glucose 1-phosphate, the end

product of the glycogen
phosphorylase reaction, is
converted to glucose 6-phosphate
by phosphoglucomutase.
Role of glycogen in muscle and liver
• The glucose 6-phosphate formed from glycogen in skeletal muscle can
enter glycolysis and serve as an energy source to support muscle
contraction.
• In liver, glycogen breakdown serves a different purpose: to release
glucose into the blood when the blood glucose level drops, as it does
between meals. This requires an enzyme, glucose 6-phosphatase, that
is present in liver and kidney but not in other tissues.
• Because muscle and adipose tissue lack glucose 6-phosphatase, they
cannot convert the glucose 6- phosphate formed by glycogen
breakdown to glucose, and these tissues therefore do not contribute
glucose to the blood
Glycogenesis
• For glycogen synthesis, sugar nucleotide is required.
• Sugar nucleotide -compounds in which the anomeric carbon of a
sugar is activated by attachment to a nucleotide through a phosphate
ester linkage.
• Sugar nucleotides are the substrates for polymerization of
monosaccharides into disaccharides, glycogen, starch, cellulose, and
more complex extracellular polysaccharides.
How are sugar nucleotide formed?
Why are sugar nucleotide needed?
• Their formation is metabolically irreversible, contributing to the irreversibility of
the synthetic pathways in which they are intermediates. The condensation of a
nucleoside triphosphate with a hexose 1-phosphate to form a sugar nucleotide
has a small positive free-energy change, but the reaction releases PPi , which is
rapidly hydrolyzed by inorganic pyrophosphatase in a reaction that is strongly
exergonic . This keeps the cellular concentration of PPi low, ensuring that the
actual free-energy change in the cell is favorable. In effect, rapid removal of the
product, driven by the large, negative free-energy change of PPi hydrolysis, pulls
the synthetic reaction forward, a common strategy in biological polymerization
reactions.
• Although the chemical transformations of sugar nucleotides do not involve the
atoms of the nucleotide itself, the nucleotide moiety has many groups that can
undergo noncovalent interactions with enzymes; the additional free energy of
binding can contribute significantly to catalytic activity.
• Like phosphate, the nucleotidyl group (UMP or AMP, for example) is
an excellent leaving group, facilitating nucleophilic attack by activating
the sugar carbon to which it is attached.
• By “tagging” some hexoses with nucleotidyl groups, cells can set
them aside in a pool for one purpose (glycogen synthesis, for
example), separate from hexose phosphates destined for another
purpose (such as glycolysis).
Glycogen synthesis
• Glycogen synthesis takes place in virtually all animal tissues but is
especially prominent in the liver and skeletal muscles.
• The starting point for synthesis of glycogen is glucose 6-phosphate.

• To initiate glycogen synthesis, the glucose 6- phosphate is converted

to glucose 1-phosphate in the phosphoglucomutase reaction:
• The product of this reaction is converted to UDP glucose by the action
of UDP-glucose pyrophosphorylase, in a key step of glycogen
biosynthesis:

• This enzyme is named for the reverse reaction; in the cell, the
reaction proceeds in the direction of UDPglucose formation, because
pyrophosphate is rapidly hydrolyzed by inorganic pyrophosphatase

• UDP-glucose is the immediate donor of glucose residues in the

reaction catalyzed by glycogen synthase, which promotes the transfer
of the glucose residue from UDP-glucose to a nonreducing end of a
branched glycogen molecule
 glycogen-branching enzyme
Also called amylo (14) to (1  6)
transglycosylase or glycosyl- (4 6)-
transferase.
Glycogen synthase cannot make the (1n6)
bonds found at the branch points of
glycogen
The glycogen-branching enzyme catalyzes
transfer of a terminal fragment of 6 or 7
glucose residues from the nonreducing end
of a glycogen branch having at least 11
residues to the C-6 hydroxyl group of a
glucose residue at a more interior position
of the same or another glycogen chain, thus
creating a new branch .
The biological effect of branching is to make
the glycogen molecule more soluble and to
increase the number of nonreducing ends
Glycogenin Primes the Initial Sugar Residues in Glycogen
Glycogen synthase cannot initiate a new glycogen chain de novo.
It requires a primer, usually a preformed (1  4) polyglucose
chain or branch having at least eight glucose residues.
Glycogenin is both the primer on which new chains are
assembled and the enzyme that catalyzes their assembly.
The first step in the synthesis of a new glycogen molecule is the
transfer of a glucose residue from UDP glucose to the hydroxyl
group of Tyr194 of glycogenin, catalyzed by the protein’s intrinsic
glucosyltransferase activity
The nascent chain is extended by the sequential addition of
seven more glucose residues, each derived from UDP-glucose;
the reactions are catalyzed by the chain-extending activity of
glycogenin.
Glycogenin remains buried within the particle, covalently
attached to the single reducing end of the glycogen molecule