GLYCOGEN METABOLISM There are four main steps in glycogen synthesis:

a. Attaching a uridine diphosphate, or UDP

 Metabolism of glycogen includes synthesis of
molecule to glucose.
glycogen by glycogenesis and breakdown of
b. Attaching the glucose part of the UDP-glucose
glycogen by glycogenolysis. This helps to regulate
molecule to a glycogen primer called
the levels of glucose in the blood. Glycogen is the
glycogenin, forming a short linear glycogen
animal storage form of glucose.
chain, which serves as a primer.
 Glucose: is a 6-carbon molecule that’s used to make
c. Adding more glucose molecules to that primer -
energy, in the form of adenosine triphosphate, or
a bit like forming a conga line.
ATP.
d. Adding branches to the glycogen molecule.
 Glucose is such an important energy source, that
our body stores excess glucose in skeletal muscle
cells and liver cells in the form of glycogen. So, starting with step one, to make UDP-glucose:
 Glycogen is basically an enormous molecule or
1. an enzyme called PHOSPHOGLUCOMUTASE
polymer, that’s made up of glucose molecules
moves the phosphate from the 6th carbon of
linked together by glycosidic bonds.
glucose-6-phosphate to the 1 st carbon, creating
 You can think of glycogen having a main chain, and
glucose-1-phosphate.
there being multiple branches sprouting off of it.
2. Next, we’ll need energy - which, uniquely,
These branches allow glycogen to be compact and
comes in the form of uridine triphosphate, or
capable of rapid addition and removal of glucose.
UTP. In the presence of glucose-1-phosphate
It’s a bit like growing a plum tree in a tiny house
and UTP, an enzyme called UDP-GLUCOSE
with a short ceiling. The short ceiling limits the
PYROPHOSPHORYLASE cuts two phosphate
tree’s vertical growth, but the tree’s able to branch
molecules off of UTP, which give the energy
off, so that it can still grow and produce many plums
necessary to complete this reaction. So only one
in a tight space.
phosphate remains attached to uridine, and
Let us say that you just wrapped up a delicious lunch - then glucose-1-phosphate is added to it. That
you had rice! makes two phosphates. So, the resulting
molecule is called UDP-glucose.
Glucose is absorbed from the intestine and our blood
sugar goes up. The pancreas responds to high blood Once many glucose molecules are converted into
sugar by secreting insulin. UDP-glucose molecules, we’re ready to create
glycogen.
Insulin acts on glucose transporters on the cell
membrane, which are called GLUTs - and makes them And in addition to prolonging the glycogen chain,
bring more glucose into all the cells in our body. there’s another byproduct of this reaction is UDP. But it
turns out that glycogen synthase can only elongate an
Inside the cell, an enzyme called hexokinase adds a
already existing glycogen chain that’s at least 4 glucose
phosphate group to its 6th carbon, creating glucose 6
molecules long.
phosphate.
3. So, if there aren’t at least four glucose
Then, glucose-6-phosphate is broken down during
molecules linked up together already, then
glycolysis, making ATP as a byproduct.
glycogen synthesis requires a protein called
Over time, ATP levels start to rise and that prevents GLYCOGENIN.
certain enzymes in glycolysis. When that happens, the
Glycogenin plays the role of fooling glycogen
extra glucose-6 phosphate can be used to make
synthase by catalyzing the attachment of 4 glucoses to
glycogen. And that usually takes place in the liver and
itself, creating a short chain connected with alpha 1,4
muscle cells.
glycosidic bonds. By doing that, it’s able to tell glycogen
synthase “Hey, we have a chain here that kind of looks
like an old glycogen molecule”.
 4. Next, there’s an enzyme called the BRANCHING
ENZYME, goes to the ends of the chain and cuts
off a chain of about 6 to 8 glucose residues in
length. THE BRANCHING ENZYME then attaches
that chain to the side of the linear glycogen
strand by creating an alpha 1,6 glycosidic bond
5. so, there’s now a bond between the 1st carbon
of the glucose on the small cleaved segment
and the 6th carbon of a glucose that’s part of
the linear chain.
6. And as soon as you’ve shortened the linear
chain, glycogen synthase will elongate it once
again. This happens over and over again,
resulting in a branched glycogen tree to serve as
stored energy. Because you’re fasting, your
blood glucose levels take a dip. In response, the
pancreas secretes the hormone glucagon and
the adrenal glands secrete epinephrine to
increase your heart rate.
Now let’s say it’s been a couple of hours since those
rice, and you decide to go for a run.
It turns out that glucagon tells the liver cells to break
glycogen down into individual glucose molecules, and
epinephrine tells skeletal muscle cells to do the same. In
both the liver and skeletal muscle cells, glycogen
breakdown begins with the branches.
1. An enzyme called GLYCOGEN PHOSPHORYLASE
cleaves the alpha 1,4 bonds between individual
glucose residues and catalyzes the transfer of a
phosphate group to the freed glucose. The
result is that the enzyme releases one glucose-
1-phosphate molecule at a time. It keeps on
doing this until exactly 4 glucose molecules
remain on the branch.
2. Next, A DEBRANCHING ENZYME literally cuts
off glycogen branches. It has a component
called 4-alpha-glucanotransferase, which
transfers 3 out of the 4 glucose molecules off of
the branch and reattaches them to the linear
glycogen chain instead, extending it as a result.
3. The same debranching enzyme has another
component known as alpha 1,6 glucosidase,
which cleaves off the alpha 1, 6 glycosidic bond
and releases a free glucose.
4. So, for each glucose that’s removed via
phosphorolysis, there’s a glucose-1-phosphate
that gets liberated, and it’s converted to
glucose-6-phosphate by phosphoglucomutase.
The difference between glycogen breakdown in the liver
and what goes on in the muscles results from the
different enzymes in those two tissues.
In liver cells, glucose-6-phosphatase removes the
phosphate off of the 6th carbon, releasing free glucose
into the bloodstream, for other organs and tissues to
use.
Skeletal muscles don’t have this enzyme, so they
simply use the glucose-6-phosphate by sending it into
the glycolysis pathway to make energy that can help
you with that run.
Glycogen metabolism is primarily regulated the two
pancreatic hormones:
 Insulin and Glucagon.
Now a general rule of thumb is, glycogen synthase is
active when it doesn’t have a phosphate, whereas
glycogen phosphorylase is active when it does have a
phosphate attached to it.
So, in liver and skeletal muscle cells, insulin binds to a
tyrosine kinase receptor on the cell surface, and that
ultimately activates a protein phosphatase which goes
around removing phosphates from glycogen synthase,
making it active, and from glycogen phosphorylase,
making it inactive.
This promotes glycogen synthesis and decreases its’
breakdown.
On the other hand, glucagon in the liver cells binds to
a G-protein coupled receptor on the cell surface, which
activates adenylyl cyclase, which converts ATP to cyclic
AMP, or cAMP. cAMP then activates protein kinase A
which adds a phosphate to glycogen phosphorylase
kinase, activating it.
Glycogen phosphorylase kinase adds a phosphate to
glycogen phosphorylase increasing its’ activity and
promoting glycogen breakdown.
It also adds a phosphate to glycogen synthase,
decreasing its activity and therefore decreasing
glycogen synthesis.