Glycogen metabolism Flashcards
how does the storage volume of glycogen differ between liver and muscle overall and per cell? what % of the cell does it account for?
there is less glycogen stored per muscel cell but more storage overall due to larger volume of muscle cells
1% in muscle and 10% in liver
What 2 reasons does a g of fat have more energy than a g of glycogen?
1) fat is more reduced and the e- can be taken to the ETC for energy
2) glycogen is stored with a large amount of water while fat is not
how do fat stores of glycogen vs fat differ?
there is about 800x more energy in fat storage than glycogen storage in most people
how long can cells be hypoxic for? how long can glycogen be used as an energy source during activity?
~20s
-90 minutes
How are glucose residues in glycogen linked? how are the branches linked? and what enzyme initiates glycogen breakdown?
1) linked by α-(1→4) glycosidic bonds
2) branch points created by α-(1→6) bonds
3) Glycogen phosphorylase catalyzes phosphorylysis of α-(1→4)
why is there no true reducing end in glycogen?
glycogenin is attached to a protein via a glycosidic bond, -preventing the free anomeric C of the molecule from functioning as a traditional reducing end
what is a true reducing end?
a free anomeric carbon that can participate in chemical rxn’s
Explain how the structure of glycogen makes it an effective molecule to add / release glucose?
It has a large number of non-reducing ends which is where we add / remove
How does glycogen phosphorylase work? what does it produce
catalyzes the phosphorylysis of α-(1→4) glycosidic bonds using inorganic phosphate to remove glucose from the non-reducing end
-does not break branched points
what is a phosphorylysis rxn?
bond cleavage using an inorganic phosphate
what moleucles are released from the phosphorylysis of glycogen? is ATP needed?
glycogen residue &
Glucose 1-phosphate
-no ATP is not used
What is the role of the glycogen debranching enzyme in glycogenolysis? why is this important?
hydrolyzes α-(1→6) bonds at branch points
-this allows glycogen phosphorylase to continue working since it can only remove glucose redisues to within 4-residues of a α-(1→6) branch point
what is a limit dextrin?
a region in glycogen molecule where phosphorylase can no longer work
explain how the debranching enzyme works?
it is a bifunctional monomer
1) transferase activity (breaks / reforms α-(1→4) )
2) hydrolysis (breaking α-(1→6) using H2O) to release free glucose
why is phosphorylysis not used in the GIT to breakdown glycogen if it does not require ATP? what type of reaction is used to breakdown glycogen in the GIT?
A phosphorylysis rxn would add a phosphate group to glycogen, releasing a phosphorylated glucose, which would not be able to enter the cell through transporters
-hydrolysis is used to breakdown glycogen in the GIT
what type of reaction is used to break down glycogen in the muscle vs GIT?
Phosphorylysis in the muscle
Hydrolysis in the GIT
what does phosphoglucomutase do? why is this important?
catalyzes the last step of glycogenolysis which converts glucose 1-phosphate to glucose 6-phosphate
-this step initiates the removal of the phosphate group from glucose so that glucose can be released out of the cell
Describe the conversion of glucose-1-phosphate to glucose-6-phosphate in glycogenolysis
Glucose 1-phosphate is converted to Glucose-1,6-biphosphate then glucose 6-phosphate by phosphoglucomutase
what enzyme in gluconeogenesis is phosphoglucomutase similar to?
phosphoglycerate mutase
-glycolysis and gluconeogenesis
what does glucose-6-phosphatase do? why it is not present in muscle tissue?
It removes the phosphate from glucose-6-phosphate producing free glucose
-muscle glycogen is used locally for energy production and doesn’t produce glucose to be sent out to other cells
why is glucose-6-phoshatase not found in the cytosol? where is it found?
it is non-specific and will work on a variety of substrates so it is only present in the ER (not cytosol)
what is the substrate transport model for glucose-6-phosphatase? what transporters are T1,T2,T3?
the movement of glucose 6-phosphate from the cytosol into the ER lumen through G6P transporter (T1) where it is hydrolyzed by G6Ptase to release glucose and Pi
-Glucose transporter (T2) and Pi T3) transporter move it out of the ER into the cytosol
G6P (T1) Glucose (T2) Pi (T3) transporter
what must happen to Glucose 1-phosphate before it can be converted to glycogen? why does this happen?
glucose-1-phosphate must be activated by UDP to form UDP-glucose
-this allows UDP-G to act as a donor to add glucose to the growing glycogen chain
explain the structure of UDP-glucose
It is a UMP molecule linked to Glucose 1-phosphate
how is a sugar nucleotide synthesized? what bonds are broken / formed? What drives this reaction forward and what enzyme is used to do this?
1 ) a UTP molecule and G1P forms UDP-glucose and Pi with UDP-glucose pyrophosphorylase
2) breaking and forming a phosphoanhydride so there is not much energy released
3) the hydrolysis of phosphoanhydride bond in inorganic pyrophosphate (PPi) to release Pi
-uses inorganic pyrophosphatase
what is the role of glycogen synthase? explain the mechanism
it catalyzes the formation of α-(1→4) glycosidic bonds
-the non-reducing end of glycogen attacks the anomeric C of UDP-glucose forming a glycogen residue 1 glucose longer and UDP
What enzyme creates branches in glycogen, and how does it do so?
glycogen branching enzyme breaks α-(1→4) to create α-(1→6) glycosidic branches by transferring a block of 6-8 glucose residues to form a new branch
Why is branching important in glycogen structure?
1) creates more non-reducing ends
2) increases solubility of glycogen
3) reduces osmotic pressure
-less water is needed to store glycogen as compared to glucose, preventing the cell from bursting
how long must the residue chain for branching be? why?
it must be at least 10 residues long in order to leave at least 4 behind
-glycogen synthase can only add to a chain at least 4 glucose residues long
how many residues away from the old branch must the new glycogen branch be?
4 residues away
What is the role of glycogenin in glycogen synthesis?
Glycogenin autocatalytically adds glucose residues to itself up to 6-7 units, after which glycogen synthase takes over
What are mature glycogen particles called, and how are they structured?
Mature glycogen particles, called glycosomes, have 12 tiers of branches with approximately 2 branches per tier and 13 residues per branch
what are the 2 forms of glycogen phosphorylase? how do these two forms behave? what state do they favour? when are they active / inactive?
phosphorylase a: more active (phosphorylated)
-favours R state
phosphorylase b: less active (dephosphorylated)
-favours T state
both are involved in the phosphorylysis of α-(1→4) glycosidic bonds in glycogen to form glucose 1-phosphate
what is the role of phosphorylase b kinase? what activates it?
it phosphorylates, phosphorylase b, bringing it to the active phosphorylase a state
-activated by glucagon (via PKA), epinephrine (via PKA), Ca+ and high [AMP]
what is the role of phosphorylase a phosphatase (PP1)? what activates this enzyme?
it converts dephosphorylates, phosphorylase ba, converting it to phosphorylase b (less active form)
-activated by insulin, G6P and glucose
how does glycogen phosphorylase in the liver act as a glucose sensor? what impact do glucose levels have on phosphorylase?
influx of glucose changes configuration of phosphorylase a, shifting it from the more active form in the R state (no glucose bound) to the less active form in the T state (glucose bound) of phosphorylase a
the change in configuration sets up the phosphate groups to be dephosphorylated once insulin signals stimulate phosphorylase a phosphatase
what is the most active form of glycogen phosphorylase?
phosphorylase a in the R state (most active form)
what is the least active form of phosphorylase?
The T form (ATP/G6P bound) of phosphorylase b
what will push phosphorylase a to the R state vs T state? which is more active?
Glucose binding will shift phosphorylase b to the T state (less active)
No glucose bound keeps it in the R state (most active)
what 2 forms is glycogen synthase found in? when is it active? when is it inactive? what regulates it?
glycogen synthase a: dephosphorylated (active)
-phosphorylated by phosphorylase b kinase (stimulated by glucagon)
glycogen synthase b: phosphorylated (inactive)
-dephosphorylated by phosphorylase a phosphatase (PP1) (stimulated by insulin)
how is glycogen synthesis / degradtaion regulated? how is G6P involved in this regulation?
reciprocally
-G6P activates glycogen synthase and inhibits glycogen phosphorylase b
what transporter deficiency is associated with glucose-6-phosphatase deficiency (type 1A disease) ?
T1 (G6P transporter), T2 (glucose transporter), T3 (Pi transporter)
which of the molecules generate the largest amount of ATP if aerobically catabloized to CO2 and H2O in hepatocytes:
Lactate, PEP, 3-PG, Acetyl coA, 1,3-BPG
*** will be on final for 10 mark Q, with a fuel source and a certail body cell
lactate
32 in liver and 30 in muscle
