18. Glycogen metabolism Flashcards
what is the purpose of muscle glycogen
provides a quick source of energy for intense aerobic or anaerobic metabolism
what is the purpose of liver glycogen
acts as a reserve that can quickly be hydrolyzed and released into the bloodstream upon low blood sugar
T or F: we ingest glycogen in our diet
true
how many glycogen residues can make up a single glycogen particle
up to 55,000
how much of the liver’s weight can be glycogen
up to 10%
how is dietary glycogen broken down
hydrolyzed by a-amylases to release glucose, which can then enter glycolysis
what is endogenous glycogen
glycogen stored in our muscles or liver
name the three enzymes involved in endogenous glycogen breakdown
- glycogen phosphorylase
- glycogen debranching enzyme
- phosphoglucomutase
what is the first thing glycogen phosphorylase does
completes a phosphorolysis reaction
where does the phosphorolysis from glycogen phosphorylase happen
on a non reducing end of glycogen
what is the result of phosphorolysis on the non reducing end of glycogen
removes the terminal glucose
what is the name of the terminal glucose cleaved from the phosphorolysis of the glycogen non reducing end
a-D-glucose 1-phosphate
what is a non reducing end
it has an anomeric carbon WITHIN a glycosidic linkage
T or F: glycogen phosphorylase will act continuously forever
false; it acts continuously on the non reducing ends of glycogen until it reaches a specific position: four glucose residues away from a a1-6 branch point
at what point does glycogen phosphorylase stop
when it is four glucose residues away from an a1-6 branch point
once glycogen phosphorylase stops, what enzyme takes over
glycogen debranching enzyme
what two types of activity does glycogen debranching enzyme have
transferase and glucosidase activity
describe the transferase activity of glycogen debranching enzyme
the enzymes transfer the next three glucose residues to a nearby non reducing end, reattaching them with a1-4 linkages
describe the glucosidase activity of glycogen debranching enzymes
they cleave the lone glucose remaining at the branch point and it is released as free glucose
once the four glucoses beside the a1-6 branch point have been removed (3 moves and 1 released), what happens
glycogen phosphorylase activity can continue! yay
recall that glycogen phosphorylase created G1P molecules by phosphorolysing the non reducing ends of glycogen. What enzyme deals with these molecules?
phosphoglucomutase
describe the role of phosphoglucomutase
it converts all the free G1P to G6P
what happens to all the G6P created by phosphoglucomutase
it can be used in glycolysis, or it can be converted to glucose in GNG so it can leave the cell
describe how G6P is made from phosphoglucomutase
the enzyme is phosphorylated on it’s Ser residue. It donates the P to the C6 of glucose, =glucose 1,6-bisphosphate. Then this product donates the P from C1 back to the enzyme (basically they trade P groups)
what happens to G6P in the muscle
it can enter glycolysis and serve as an energy source to support muscle contraction
what happens to G6P in the liver
it needs to be converted to glucose to be released into the bloodstream to maintain blood sugar between meals
what is the function of glucose 6-phosphatase
converts G6P to glucose
where is G6Pase located
the liver, embedded in the ER membrane
which side of the ER membrane is the G6Pase active site
the luminal side
how many transporters are involved to move G6P, glucose, and Pi across the ER membrane
3
describe the movement of G6P, glucose, and Pi across the ER membrane
T1 brings G6P into the lumen where it’s converted into glucose and Pi via G6Pase. Both leave the lumen through T2 and T3 respectively. GLUT2 allows glucose to leave the liver cell
what is the benefit of having the G6P–> glucose reaction happen in the ER lumen of the liver
if we remove the phosphate in the cytosol, this is the same place as glycolysis, which would immediately add the phosphate back via hexokinase
T or F: glycogen synthesis takes place in all animal tissues
true
where is glycogen synthesis prominent
liver and skeletal muscles
what is the name of the key enzyme in glycogen synthesis
glycogen synthase
describe the use of a sugar nucleotide intermediate in glycogen synthesis
the anomeric carbon of a sugar phosphate is attached to an NDP. This primes the molecule, as NMP/NDP will later make a good leaving group
T or F: once the anomeric carbon of a sugar phosphate is attached to an NDP, it can unattach
false; this process is irreversible
once the sugar phosphate is attached to an NDP, what happens
the oxygen on the sugar phosphate serves as the nucleophile, attacking the alpha phosphate on an NTP. Leaves us with the sugar attached to NDP, and leftover PPi
what happens to the leftover PPi in glycogen synthesis
it’s quickly hydrolyzed into two phosphates
T or F: the hydrolysis of PPi into two phosphates is exergonic
true
how is glycogen synthesis initiated
phosphoglucomutase works in reverse: G6P –> G1P
after G1P is formed in glycogen synthesis, what happens
a sugar nucleotide is formed: G1P + UTP –> UDP-glucose + PPi
what is the reactant for glycogen synthase
UDP-glucose
as the reactant for glycogen synthase, what does UDP-glucose do
it adds glucose to the non reducing ends of a growing glycogen chain
T or F: glycogen synthase is able to form the a1-6 bonds at glycogen branch points
false; it cannot
what is used to make the glycogen a1-6 branch points
a glycogen branching enzyme
describe how the glycogen branching enzyme is used
it transfers a fragment of 6-7 glucose residues from the non reducing end to the C6 hydroxyl of a more interior glucose, and then glycogen synthase can extend the new branch
what are the benefits of lots of branches of glycogen
branching improved the solubility, and increases the number of non reducing ends
T or F: glycogen synthase can initiate a new glycogen polymer on its own
false; it cannot
what does glycogen synthase need in order to initiate a new glycogen polymer
a primer
what initiates the primer in glycogen synthesis
glycogenin
what do you start with in glycogen synthesis (in regards to glycogenin)
UDP-glucose
what does UDP-glucose do in glycogen synthesis
the glucose is donated to the OH group of Tyr of glycogenin = glucosylated Tyr
what catalytic activity describes the formation of glucosylated Tyr
transferase activity (glucose transfers from UDP-glucose to the OH of Tyr)
once Tyr is glucosylated, what happens
glycogenin adds seven more molecules to the original one (each derived from UDP-glucose)
what activity describes the addition of the 7 glucose molecules onto the other one via glycogenin
chain extending activity
in glycogen synthesis, once we have the 8 glucose primer, what happens
glycogen synthase can take over
T or F: after the initiation of glycogen synthesis, the primer leaves
false; glycogenin and the primer remain in the molecule
how many tiers does the glycogen particle have
12
how many residues composes each tier of glycogen
12-14 residues in each tier
how big is a glycogen molecule
21 nm (as big as a ribosome)
what plays a role in the regulation of both glycogen phosphorylase and glycogen synthase
reversible phosphorylation
how are the two forms of glycogen phosphorylase and glycogen synthase denoted
a and b forms
describe the a form of glycogen phosphorylase and glycogen synthase
it’s more active
describe the b form of glycogen phosphorylase and glycogen synthase
it’s less active
describe the structure of glycogen phosphorylase
homodimer
describe the a form of glycogen phosphorylase
phosphorylated at two serine residues
describe the b form of glycogen phosphorylase
deprotonated at both serine residues
what enzyme phosphorylates glycogen phosphorylase b to create a
phosphorylase b kinase
what happens when we have the a form of glycogen phosphorylase
a form = active = glycogen breakdown
what activates phosphorylase b kinase
glucagon; PbK gives us the active form of the enzyme which causes glycogen breakdown = glucose, so when we have glucagon (low glucose) we want the a form
what enzyme dephosphorylated the a form into the b form
phosphoprotein phosphatase 1 (PP1)
when do we want glycogen phosphorylase to be active
when we want glycogen breakdown
how do we get glycogen breakdown in the muscle
release of adrenaline or epinephrine (ie after exercising) leads to glycogen breakdown
how do we get glycogen breakdown in the liver
when we’re hungry/secreting glucagon
name the two cell types where glycogen breakdown occurs
myocytes (muscle) and hepatocytes (liver)
in glycogen breakdown in the muscle, what binds to a GPCR
epinephrine
in glycogen breakdown in the liver, what binds to a GPCR
glucagon
what is the name of GPCR
G-protein coupled receptor
after either epinephrine or glucagon binds to the GPCR in glycogen breakdown, what happens
signal cascade
what is the result of the signal cascade in glycogen breakdown
the cascade ensures an amplification of the signal so that a huge number of G1P molecules are freed from glycogen
what term is used to relate the glycogen phosphorylase enzymes (one is in muscle, one in liver)
isozymes
in the muscle, what activates phosphorylase b kinase to make the a form of the phosphorylase
Ca2+ and AMP activate it, because they signify a contracting muscle, so the a form is made which breaks down glycogen
in the liver, what inhibits phosphorylase a activity
glucose
other than inhibiting the phosphorylase a activity, what role does glucose play when it binds
it binding promotes a conformational change, exposing the phosphorylated Ser residues to PP1 for cleavage, giving us the inactive form
describe how we convert to the b form of phosphorylase
glucose binds to the a form to inhibit it, a conformational change happens, the phosphorylated Ser residues are now exposed to PP1 for cleavage = b form (inactive)
in glycogen synthase, which form is active; a or b
a is active
in glycogen synthase, which form is phosphorylated; a or b
b is phosphorylated!! (tricky)
what enzyme phosphorylated glycogen synthase to make the b form
glycogen synthase kinase 3 (GSK3)
what enzyme dephosphorylated the b form of glycogen synthase to get the a form
phosphoprotein phosphatase 1 (PP1)
what two molecules bind to glycogen synthase to expose the phosphates to PP1
glucose and G6P
what form of glycogen synthase does insulin promote
a form (active)
how does insulin promote the a form of glycogen synthase
it blocks GSK3 (preventing the inactive form), and it activates PP1 (to dephosphorylate the enzyme to get the active form)
insulin binding to an insulin receptor initiates a signal cascade that activates which molecule
protein kinase B
what role does protein kinase B play in glycogen synthase regulation
PKB phosphorylates/inactivates GSK3, leading to more glycogen synthase in the active form
big picture: when we eat a meal, there’s high blood glucose, insulin secretion, decrease in glycogen breakdown. Describe how this happens
insulin inhibits GSK3 and activates PP1, fully activating glycogen synthase. Glucose enters the cell and removes hexokinase IV from the nucleus, so it enters the cytosol to make G6P which can be used for either glycolysis or glycogen synthesis.
big picture: after a meal, there’s low blood glucose, glucagon secretion, increase in glycogen breakdown. Describe how this happens
protein kinase A mediates all effects of glucagon. It phosphorylated and actives phosphorylase kinase and FBPase-2. It phosphorylated and deactivates PFK2 and pyruvate kinase in the liver. Liver produces lots of G6P by glycogen breakdown and GNG, and then G6Pase makes glucose to be exported to the blood
