3. • Glycogen is a chain of glucose subunits held
together by( α 1,4 glycosidic bonds),
glycogen is a branched structure. At the
branch points, subunits are joined by ( α1g6
glycosidic bonds).
• Branches occur every 8-10 residues.
4.
5.
6. Glycogenesis is the process of
Glycogen synthesis
• Glycogen is synthesized when blood
glucose levels are high .
• Glucose is converted into glucose-6phosphate by the action of :
Hexokinase catalyses this reaction in most
tissues.
In the liver and pancreas there is an extra
enzyme; Glucokinase exhibiting different
kinetic properties.
8. • This state is reflected inside liver cells by
the presence of high levels of glucose-6phosphate. G6P is converted to G1P by
phosphoglucomutase.
• This reaction is analogous to the reaction
catalyzed by phosphoglycerate mutase in of
glycolysis, and proceeds by a similar
mechanism, with a bisphosphate
intermediate.
9.
10. • Conversion of G1P into glycogen is
energetically unfavorable, so another source
of energy input is required.
• This comes in the form of hydrolysis of
UTP (uridine triphosphate). The highenergy phosphoanhydride bonds in UTP are
equivalent to those in ATP. First, UTP is
combined with G1P by UDP-glucose
pyrophosphorylase.
11.
12.
13. :::Next, glycogen synthase catalyzes the addition of this
activated glucose subunit to the C4-hydroxyl group at the
end of a glycogen chain (the non-reducing end).
14. • After the chain is more than four residues long, glycogen
synthase takes over. Glycogenin remains bound to the
reducing end of glycogen (the C1 hydroxyl group at the
right side of the pictures). Glycogen synthase works
efficiently only when it is bound to glycogenin.
• Thus the number of glycogen granules in a cell is
determined by the number of glycogenin molecules
available, and the size of the granules is limited by the
need for physical association between glycogenin and
glycogen synthase. When the granule grows too large, the
synthase stops working.
15. • Formation of branches is catalyzed by
"branching enzyme",( amylo (α-1,4ـــα1,6)
transglycosylase).
• This enzyme breaks off a chain of about 5 to 8
glucose residues from the growing end of
glycogen by hydrolyzing an( α 1,4 glycosidic
linkage), and transfers the short chain to another
residue in the same glycogen molecule that is at
least four residues away from the cleavage point,
forming an( α 1,6 glycosidic linkage)
16. After the transfer, both the old C4 end and the newly exposed C4 end
can be elongated by glycogen synthase.
As soon as the new ends are long enough, they can again be
branched. A mature glycogen granule may have seven layers of
branches.
17. • Branching gives glycogen two advantages
over starch as a storage form of glucose.
• First, it is more soluble than its unbranched
cousin.
• Second, the exposure of more C4
(nonreducing) ends means that glycogen
can be both sythesized and degraded more
quickly than a single starch chain with the
same number of residues.
18. Control and regulations
Epinephrine (Adrenaline)
• 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 adenosine
monophosphate AMP from Adenosine triphosphate (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.
19. • Returning to glycogen phosphorylase, the less active
"b" form can itself be activated without the
conformational change. 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.
20. Insulin
• Insulin has an antagonistic effect to adrenaline.
• When insulin binds on the G protein-coupled receptor,
the alpha subunit of Guanosine diphosphate GDP in the
G protein changes to Guanosine-triphosphate GTP and
dissociates from the inhibitory beta and gamma subunits.
• The alpha subunit binds on adenylyl cyclase to inhibit its
activity.
• As a result, less cyclic AMP then less protein kinase A
will be produced. Thus, glycogen synthase, one of the
targets of protein kinase A, will be in nonphosphorylated form, which is the active form of
glycogen synthase.
21. Calcium ions
• Calcium ions or cyclic AMP (cAMP) 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.
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24. Regulation
• Glycogenolysis is regulated hormonally in
response to blood sugar levels by glucagon
and insulin, and stimulated by epinephrine
during the fight-or-flight response.
• In myocytes, glycogen degradation may
also be stimulated by neural signals.
