Phosphorylase b and phosphorylase a exist in equilibrium between
an active R state and less active T state
Phosphorylase b is usually inactive because
the equilibrium favors the T state
Phosphorylase a is usually active because
the equilibrium favors the R state
In the T state,
the active site is partly blocked by a regulatory structure
active site is
unobstructed in the R state
Key role of the liver is to
maintain adequate blood levels of glucose
as a result, the default state of liver phsophorylse
liver phosphorylase
prepared to generate blood glucose unless signaled otherwise
negative regulator of liver phosphorylase
glucose
it facilitates the transition from the R state to the T state
Muscle phosphorylase
regulated by the intracellular energy charge
default form of phosphorylase in muscle is the
b form in the T state
when energy is needed, as signaled by an increase in the concentration of AMP the phosphorylase binds AMP which stabilizes the R state
T state of muscle phosphorylase is stabilized by
ATP and glucose 6 phosphate
What enzyme is responsible for the conversion of glycogen phosphorylation from the unphosphorylated b state to the a state
phosphorylase kinase
how is phosphorylase kinase activated
by both phosphorylation and Ca2+ binding
What is phosphorylase kinase phosphorylated by
protein kinase A
What is the delta subunit of phosphorylase
calcium sensor calmodulin
When is phosphorylase kinase maximally active?
when phosphorylated and
bound to calcium
Glucagon (Liver) and Epinephrine (Muscle) initiate protein cascades that result in what
production of cAMP
what is adenylate cyclase activated by
G alpha
What does cyclic AMP activate
protein kinase A (PKA) which phosphorylates and completes the activation of phosphorylase kinase
What activates glycogen degradation
phosphorylase kinase converting glycogen phosphorylase b to the a form
Glycogen breakdown =
must be rapidly turned off when necessary
How is glycogen degradation turned off
1) the inherent GTPase activity of the G protein renders these proteins inactive
2) Phosphodiesterase converts CAMP to AMP which does not stimulate protein kinase A
3) Protein phosphatase 1 ( activated by insulin signaling ) removes phosphoryl groups from phosphorylase kinase and glycogen phosphorylase, thereby inactivating the enzymes
Glycogen synthesis proceeds via an activated form of glucose:
UDP glucose
What is UDP glucose synthesized by
UDP glucose pyrophosphorylase
reaction is subsequently irreversible by the hydrolysis of pyrophosphate
Glycogen synthase catalyzes the transfer of what
glucose from UDP glucose to a growing chain
key regulatory enzyme in glycogen synthesis
glycogen synthase
What does glycogen synthase do
transfers a glucose moiety from UDP glucose to the C4 terminal residue of glycogen chain to form an alpha 1-4 glycosidic bond
extends primer
can extend the branched polymer
What does glycogen synthase require
an oligosaccharide glucose residues as primer
primer is synthesized by glycogenn
What is glycogenin
a dimer of two identical subunits
each subunit generates an oligosaccharide of glucose residues 10-20 molecules long
Glycogen branching enzyme remodels the growing glycogen chain and introduces what
alpha 1,6 linked branches
A branching enzyme generates what
branches by cleaving an alpha 1-4 linkage and taking a block of approximately 7 glucoses and synthesizing an alpha 1,6 linkage
An efficient way to store glucose
making glycogen
Glycogen
highly branched homopolymers of glucose present in all tissues
Largest stores of glycogen are in the
liver and muscle
What does the liver do?
it breaks down glycogen and releases glucose to the blood to provide energy for brain and RBCs
Muscle glycogen stores are mobilized to
provide energy for muscle contraction
Glycogen storage particle storage:
glycogenic protein at center
alpha 1,4 linked glucose chains with alpha 1,6 branch every 10 residues
non reducing end glycogen molecule exposed on the surface
Why is glycogen highly branched?
glycogen particle structure allows for rapid mobilization of glucose reserves
what 4 enzymes are needed for complete glycogen breakdown
Glycogen phosphorylase
Glucosyltransferase
Glycogen phosphorylase
degrades glycogen from the nonreducing ends of the glycogen molecule
catalyzes a phosphorolysis reaction that yields glucose 1- phosphate
specific for the hydrolysis of alpha 1,4 glycosidic linkages and it cannot cleave near branch points
Complete breakdown of glycogen requires what
remodeling of the glycogen molecule
Glucosyltransferase (GT)
shifts a small oligosaccharide near the branch point to a nearby chain, thereby making the glucose moieties accessible to the phosphorylase
alpha-1,6-glucosidase
deb ranching enzyme
cleaves the alpha 1-6 bond at the branch point releasing a free glucose
Phosphoglucomutase form glucose 6 phosphate from glucose 1 phosphate via what
a glucose 1,6 bisphosphate intermediate
Glucose 6 phosphatase generates what
free glucose from glucose 6 phosphate in liver
Glucose 6 phosphatase is absent in most other tissues:
in muscle tissue, the glucose 6 phosphate generated by the breakdown of glycogen feeds into glycolysis and ATP production
Glycogen phosphorylase is regulated by:
reversible phosphorylation and by allosteric effectors
Key regulator enzyme for glycogen degradation
glycogen phosphorylase
The liver and muscle express different isoforms of
glycogen phosphorylase with different regulation
Glycogen phosphorylase exists in two forms:
a less active b form and a more active a form
A form of glycogen phosphorylase
differs from B form in that a serine residue (14) is phosphorylated
Both the a form and b form of glycogen phosphorylate display
R to T equilibrium
B form of glycogen phosphorylase
the T state is favored while in the a form the R state is favored
unphosphorylated
Phosphorylation is stimulated by what 2 hormones
glucagon and epinephrine (adrenaline)
Phosphorylation alters the active site such that
alpha helices that partially block the active site in the b form are removed
How many molecules of ATP are required to incorporate dietary glucose into glycogen
2
complete oxidation of glucose derived from glycogen yields how many ATP
31
Glycogen synthase is inactive where
in the phosphorylated form
opposite of glycogen phosphorylase
Keyallosteric effector for glycogen synthase
is the conversion of the b form in the T state to the active R state of the b form by binding glucose 6 phosphate
What does glycogen synthase kinase do
phosphorylase glycogen synthase, inactivating it
What does protein phosphatase 1 do
dephosphorylates glycogen synthase , activating it
Glycogen synthesis is inhibited by the same glucagon and epinephrine signaling pathways that stimulate what
glycogen breakdown
glucagon or epinephrine
unregulated glycogen phosphorylase
and downregulate glycogen synthase
What inhibits glycogen synthesis
phosphorylation of glycogen synthase by protein kinase A to form glycogen synthase
In liver, high glucose hind to what
glycogen phosphorylase a and inhibits it
High blood glucose levels
glycogen degradation in the liver is inhibited
glycogen synthesis is stimulated
How is PP1 activated?
by the conversion of glycogen phosphorylase a from the R state to the T state by the binding of glucose
What does PP1 do
converts glycogen metabolism from a degradation mode to a synthesis mode