Glycogen Metabolism Flashcards
Osmotically inactive and readily mobilized form of glucose
Glycogen
Glycogen is a branched long chain _______ of glucose molecules
Homopolymer
Glycogen is ____ layers of glucsoe with approx. ________ glucose residues
12, 55,000
In glycogen glucose is linked together via _____
alpha 1-4 glycosidic bonds
Glycogen has branch points every ____ residues formed via ________ between glucose monomers of separate chains
12, via alpha 1,6 glycosidic bonds
The non-reducing ends of glycogen each contain a terminal glucose with a free hydroxyl group at
C4
The Reducing end of glycogen has a glucose monomer connected to a protein called a
Glycogenin (note that glycogenin is a complex with Mn, UDP and maltohexaose)
Glycogenin helps to make a _____ which is crucial for glycogen synthesis
primer
Glycogen is stored in the
liver, muscle, and other tissues
Glycogen can be present as ______ which not only contain glycogen but also the enzymes needed for its metabolism
Granules
What is the function of liver glycogen
regulates overall blood glucose levels
What is the function of muscle glycogen
provides reservoir of fuel (glucose) for physical activity for muscles
pathways for glycogen synthesis and degradation are regulated
independently
What are some modes of regulation of glycogen synthesis and degradation
allosteric control
covalent modification through reversible phosphorylation of key enzymes
Hormonal control
what are the three pathways that glucose 6-P can take
it can enter glycolysis
free glucose for release into blood stream
pentose phosphate pathway- NADPH and ribose derivative
What are the names of the key enzymes in glycogenolysis
Glycogen phosphorylase (GP)( rate limiting enzyme)- catalyzes the cleavage of glycogen, chain shortening occurs at the nonreducing end of the polmer
Transferase- transfers block of 3 of the remaining 4 glucose to the non-reducing end of the main chain forming an alpha- 1,4 bond
Debranching enzyme or alpha 1,6-glucosidase- cleaves the alpha 1,6 bond of the single remaining glucose residue to release the free glucose
Phosphoglucomutase- converts glucose 1-P to glucose 6-P
Glucose 6-Phosphatase- Cleaves off phosphate and makes glucose
What is the rate limiting step of glycogenolysis
Glycogen phosphorylase (GP)
Where does glycogen phosphorylase (GP) shorten the chain
at the non-reducing end of glycogen polymer
glycogen phosphorylase does not require ATP but instead adds a ______ and releases glucose residue as glucose-1-P
Orthophosphate
Glycogen phosphorylase (GP) uses what as a cofactor
Pyridoxal phosphate (vitamin B6)
Phosphorolysis of glucose residues continues till the Glycogen phosphorylase (GP) gets within ____ residues of the alpha-1,6 linkage of a branch point
4
What enzyme transfers a block of 3 of the remaining 4 glucoses to the non-reducing end of the main chain forming an alpha-1,4 bond
Transferase
What enzyme cleaves the alpha 1,6 bond of the single remaining residue to release the free glucose
Debranching enzyme/ alpha-1,6- glucosidase
The free glucose cleaved of the glycogen by debranching enzyme/alpha 1,6 glucosidase is phosphorylated by
hexokinase
What is the function of phosphoglucomutase
it converts Glucose 1-P to glucose 6-P
(Note that the phosphoryl group is transferred form the enzyme to the substrate, and a different phosphoryl group is transferred back to restore the enzyme to its initial state
Glucose 6-Phosphatase is only located in
The liver
What is the function of glucose 6-phosphatase
it converts Glucose 6-Phosphate into glucose
Glycogen phosphorylase is regulated by
several allosteric effectors (signal energy state of the cell) reversible phosphorylation (responsive to hormones)
Glycogen phosphorylase exists in an active a form located in the _____ and an incactive b form located in the _____
liver, muslce
Glycogen phosphorylase b form is activated to a form by what enzyme
phospohrylation fo a single serine residue with phosphorylase kinase (with 2 ATP)
____ is a allosteric inhibitor of phosphorylase a in the liver and moves it to the T (tense) state
glucose
b phosphorylase is in the R (relaxed state) when what is high
AMP (binds to active site and stablilizes conformation of b in the active R state)
(note that this occurs during muscle contraction because ATP is converted to AMP by myosin and adenylate kinase signaling the GP to breakdown glycogen)
What are negative allosteric regulators of glycogen phosphorylase
ATP and glucose 6-P
The conversion of glycogen phosphorylase a to b is initiated by
hormones
Phosphorylase kinase becomes active with
Ca2+ leads to partly active then phosphorylase kinase A and hormones make it fully active
Phosphorylase kinase has 4 subunits what are they
(alpha, beta, gamma, delta)x4
Phosphorylase Kinase is a large protein of about
1300kD
What are the subunits of phosphorylase kinase
alpha- phosphorylation site
beta- phosphorylation site
gamma- active site
delta- Calmodulin
Epinephrine and glucagon do what to glycogen
induce glycogen breakdown
glucagon and epinephrine work through
G protein coupled receptors (GPCR) specifically the 7TM receptor
The liver and muscle forms of Glucose phosphorylase are products of separate genes. called
isozymes
Both the liver and muscle forms of glycogen phosphorylase are activated by ____ and inhibited by ___ and ___
pohosphorylation by PK and inhibited by ATP and G6P
(note muscle is also allosterically activated via AMP and in the liver it is inactivated via free glucose but unaffected by AMP)
Mutation in the liver glycogen phosphorylase results in
Hers disease
Mutation in the muscle glycogen phosphorylase results in
McArdle syndrome
