Glycogenesis is the process of glycogen synthesis, in which glucose molecules
are added to chains of glycogen for storage. This process is activated
during rest periods following the Cori cycle, in the liver, and also activated
by insulin in response to high glucose levels, for example after a
carbohydrate-containing meal. Steps
Glucose is converted into glucose-6-phosphate by the action of
glucokinase or hexokinase. Glucose-6-phosphate is converted into
glucose-1-phosphate by the action of phosphoglucomutase, passing through the
obligatory intermediate glucose-1,6-bisphosphate.
Glucose-1-phosphate is converted into UDP-glucose by the action of the enzyme
UDP-glucose phosphorylase. Pyrophosphate is formed, which is later hydrolysed by
pyrophosphatase into two phosphate molecules.
Glycogenin, a homodimer, has a tyrosine residue on each subunit that serves as
the anchor for the reducing end of glycogen. Initially, about eight
UDP-glucose molecules are added to each tyrosine residue by glycogenin, forming
α(1→4) bonds. Once a chain of eight glucose monomers
is formed, glycogen synthase binds to the growing glycogen chain and adds
UDP-glucose to the 4-hydroxyl group of the glucosyl residue on the non-reducing
end of the glycogen chain, forming more α(1→4) bonds in the process.
Branches are made by glycogen branching enzyme→α(1:6)transglycosylase), which
transfers the end of the chain onto an earlier part via α-1:6 glycosidic bond,
forming branches, which further grow by addition of more α-1:4 glycosidic units.
Control and regulations Glycogenesis responds to hormonal
control. One of the main forms of control is the
varied phosphorylation of glycogen synthase and glycogen phosphorylase.
This is regulated by enzymes under the control of hormonal activity, which is
in turn regulated by many factors. As such, there are many different possible
effectors when compared to allosteric systems of regulation.
= Epinephrine= Glycogen phosphorylase is activated by
phosphorylation, whereas glycogen synthase is inhibited.
Glycogen phosphorylase is converted from its less active "b" form to an active
"a" form by the enzyme phosphorylase kinase. This latter enzyme is itself
activated by protein kinase A and deactivated by phosphoprotein
phosphatase-1. Protein kinase A itself is activated by
the hormone adrenaline. Epinephrine binds to a receptor protein that
activates adenylate cyclase. The latter enzyme causes the formation of cyclic
AMP from ATP; two molecules of cyclic AMP bind to the regulatory subunit of
protein kinase A, which activates it allowing the catalytic subunit of
protein kinase A to dissociate from the assembly and to phosphorylate other
proteins. Returning to glycogen phosphorylase, the
less active "b" form can itself be activated without the conformational
change. 5'AMP acts as an allosteric activator, whereas ATP is an inhibitor,
as already seen with phosphofructokinase control, helping to change the rate of
flux in response to energy demand. Epinephrine not only activates glycogen
phosphorylase but also inhibits glycogen synthase. This amplifies the effect of
activating glycogen phosphorylase. This inhibition is achieved by a similar
mechanism, as protein kinase A acts to phosphorylate the enzyme, which lowers
activity. This is known as co-ordinate reciprocal control. Refer to glycolysis
for further information of the regulation of glycogenesis.
= Insulin= Insulin has an antagonistic effect to
epinephrine signaling via the beta-adrenergic receptor. When insulin
binds to its receptor, it results in the activation of Akt which in turn
activates Phosphodiesterase. PDE then will inhibit cyclic AMP action and cause
inactivation of PKA which will cause Hormone Sensitive Lipase to be
dephosphorylated and inactive so that lipolysis and lipogenesis is not
occurring simultaneously. = Calcium ions=
Calcium ions or cyclic AMP act as secondary messengers. This is an example
of negative control. The calcium ions activate phosphorylase kinase. This
activates glycogen phosphorylase and inhibits glycogen synthase.
See also Glycogenolysis
Glycogen synthase Glycogen storage disease
External links The chemical logic of glycogen synthesis