HOME
Sweet Tooth
Sugar is released from glycogen by the enzyme glycogen
phosphorylase. It clips glucose from the chains on the surface of a glycogen
granule. The enzyme is a dimer of two identical subunits (colored green and blue
in the structure here, from PDB entry
6gpb). In the upper illustration, two nucleotides, in red, are bound at the
entrance to the active site, which is found in a deep cleft. The yellow
molecules are short chains of sugars similar to the ends of glycogen chains,
which bind into another cleft that the enzyme uses to grip the glycogen granule.
In its cleavage reaction, glycogen phosphorylase uses a phosphate molecule,
connecting it to the sugar as it is released. A second enzyme,
phosphoglucomutase, then shifts the position of the phosphate to a neighboring
carbon atom in the sugar, making the sugar ready for breakdown by glycolysis.
Moderation
As you might imagine, this process is highly regulated.
Traffic of sugar into and out of storage in glycogen is used to control the
level of glucose in the blood, so glycogen phosphorylase must be activated when
sugar is needed and quickly shut down when sugar is plentiful. It is controlled
in several ways. First, the enzyme is activated by adding a phosphate molecule
to a serine amino acid (serine 14) on the back side of the enzyme, shown in
bright green and blue in the lower illustration. The phosphate causes a large
shift in the shape of the enzyme (shown on the next page), shifting it into the
active conformation. Two special enzymes control the addition and removal of
this phosphate, based on levels of the sugar-monitoring hormones insulin and
glucagon, and other hormones such as epinephrine (adrenaline).
Also, binding of other molecules can modify the activity of the molecule. For
instance, AMP (adenine monophosphate) binds to a different site on the back side
of the molecule (shown in red on the lower illustration), causing the same shift
to the active conformation. This is useful, because AMP is a product of ATP
breakdown and will be more plentiful when energy levels are low and more sugar
is needed.
Back