Lecture 34: Glycogen Metabolism Flashcards
Wednesday 4th December 2024
How branched is glycogen?
very highly branched
What does the branching of glycogen help with?
Branching enables rapid synthesis and breakdown (more accessible ends for enzymes).
Is it true that storing glucose as glycogen reduces osmotic pressure compared to storing free glucose?
Yes, and allows cells to store large amounts of glucose without altering the osmotic pressure significantly.
What is glycogen stored as?
Insoluble granules in the liver and the skeletal muscle
What would glucose require to be used directly as storage?
Storing free glucose would require a lot of water due to its solubility and would cause issues with osmotic balance
What is the store of glucose in the liver used to regulate?
Blood glucose levels
What is the store of glucose in the muscles used to regulate?
Solely for the muscle
Glycogen –> Glucose-1-P –> Glucose-6-P (2nd step of glycolysis)..
Why does the body need to use glycogen for energy storage in addition to the more abundant fat?
Fatty acids cannot be metabolised anaerobically
Blood glucose must be maintained to serve as fuel for the brain
Animals cannot convert fatty acids to glucose
What are the only organisms that can turn fatty acids into glucose?
Plants and bacteria
By which pathway do plants and bacteria turn fatty acids into glucose?
The Glyoxylate pathway. Instead of being oxidised, Isocitrate is cleaved and glyoxylate and succinate are formed. Succinate can then continue on in the citric acid cycle in order to regenerate oxaloacetate. The glyoxylate can react with a Acetyl CoA and malate can be reformed. Extra intermediate is generated (an extra malate from glyaxolate), so one intermediate can be taken out and turned into glucose
What 2 bonds does glycogen have?
α-1,4 glycosidic bonds and α-1,6 glycosidic bonds
What is sued to cleave the bonds in glycogen?
A phosphate, not water
Describe glycogen breakdown (branch points)
1) α-1,4 glycosidic bonds on each branch are cleaved till 4 residues left
2) Transferase shifts a block of 3 residues from one branch to the other
3) The branch point residue (green) is removed by α-1,- glycosidase (debranching enzyme) leaving a linear chain
What does enzyme transferase do?
Moves a block of glucose residues to an adjacent chain.
What does the debranching enzyme do?
Removes the remaining glucose molecule linked by an alpha-1,6 bond.
In terms of energy, what is UTP the same as?
ATP
Where does UDP come from?
UTP
Does glycogen synthesis occur by a “reversal” of the phosphorolytic cleavage?
No
Is glycogen synthesis endergonic?
Yes, requires the input of energy in the form of UTP
What reaction occurs in glycogen synthesis?
Glucose-1-phosphate + UTP –> UDP-glucose + Pyrophosphate
(pyrophosphate wil get cleaved into 2 inorganic phosphates, which will help with the release of more energy).
What happens when UDP-glusoe reacts with glycogen?
UDP and a glycoegn with an extra glucose attached by a1,4 glycosidic bond will be formed. This is catalysed by glycogen synthase.
What is an important step that must occur before glycogen synthesis?
priming
What is the name of the primer that is required in glycogen synthesis?
Glycogenin
Describe glycogenein (starts glycogen molecule)
The glycogen primer consists of four or more α-1,4 linked glucose residues attached to a tyrosine in the protein
Is it true that a separate branching enzyme will transfer blocks of ~ 7 glucose resisdues to interior sites and attach to the α-1,6 linkages?
Yes
What does Andersen’s disease cause?
Causes a lack of the branching enzyme that will transfer blocks of ~ 7 glucose resisdues to interior sites and attach to the α-1,6 linkages. This means that the glycogen will only be linear. People with Andersen’s disease usually die of liver failure at an early age
What causes Andersen’s disease?
A mutation in the branching enzyme
Are there a range of glycogen-storage diseases?
Yes
Can glucose-1-P and glucose-6-P interchange with each other?
Yes
What does glycogen phosphorylase break down glycogen into?
Glucose-1-P
How is glycogen metabolism regulated?
- The enzymes Glycogenphosphorylase and glycogensynthase are reciprocally regulated (one active, the other inactive) to prevent energy waste. (cellular level).
- The hormones glucagon, adrenaline and insulin regulate enzymes by phosphorylating them. (hormonal)
- Also allosteric regulation by effectors signaling energy state of the cell
What is phosphorylase actiavted by?
Phosphorylation
What is glycogen synthase inactivated by?
phosphorylation
What happens when there are low blood glucose levels?
- Low insulin concentration and so glucagon is released.
- Phosphorylase activation and glycogen synthase inactivation
- Glycogen breakdown into glucose.
- (Stress: Adrenalin release, same activation and inactivation as glucagon release
)
What happens when there are high blood glucose levels?
- High insulin, low adrenalin and glucagon
- Glycogensynthase activation and phosphorylase inactivation
- Glycogen synthesis
What type of enzyme is glycogen phosphorylase?
An allosteric enzyme
What are the 2 states of glycogen phosphorylase?
Phosphorylase a (in relaxed state) (active)
Phosphorylase b (in tense state) (inactive)
is there a conformational change between the 2 states?
Yes
Phosphorylation
Equilibrium between the active relaxed (R) state and the inactive tense(T)state
Adding on the phosphate group shifts the equilibrium to the R state.
Muscle cell energy status
(phosphorylase b)
- Enzymemostly inactive, muscles resting msot of the time.
- If AMP levels go up, using lots of ATP, moving around, AMOP will bind to nucleotide binding site and overrule and shift enzymes to R state, so that it becomes active.
- If lots of ATP, the opposite happens.
Liver
- Normal form is active, breaking donw glycogen to prodce glucose, energy
- If too much glucose, gluxose binds as allosteric regulator and shift equilibrium from R state to T state, overules, disregards the fact that enzme is in phosphorylated state.
What are muscle and liver phosphorylases examples of?
isozymes
What is an isozyme?
Multiple forms of an enzyme that catalyze the
same reaction but differ from each other in their primary
structure, kinetic properties and allosteric regulation.
What do isozymes normally originate from?
gene duplication
Glucose Homeostasis
high blood glucose
Pancreas secretes insulin.
Liver stores glucose as glycogen.
Results in a drop in blood glucose levels.
Glucose Homeostasis
low blood glucose
Pancreas secretes glucagon.
Liver breaks down glycogen to release glucose.
Blood glucose levels increase.
what happens if you’re fasting?
Glucagon is released from the pancreas. Liver will respond and start releasing glucose into the bloodstream
What causes Epinephrine to be released from the adrenal medulla?
Stress/exercise. Also causes liver to release glucose into the bloodstream.
Does the liver respond to both glucagon and adrenaline in the same way?
Yes
Does adrenaline act on both the muscle and the liver?
Yes
Will the muscles repsond to glucagon?
No
What happens when adrenaline acts on the muscle?
Glycogen –> Glucose –> Pyruvate –CO2 (or lactate under anaerobic conditions)
(The lactate will be secreted into the bloodstream and will be taken into the liver. The liver will then use lactate to generate more glucose. More glucose will then be released into the bloostream that can reach the muscle and helm generate more energy).
Describe the Corri cycle
- Occurs under anaerobic conditions (e.g., sprinting):
- Muscle produces lactate from glucose via glycolysis.
- Lactate is transported to the liver.
- Liver converts lactate back to glucose through gluconeogenesis.
- Glucose is sent back to muscle.
Why is the Corri cycle important?
Prevents futile cycles by separating processes between organs.
Supplies energy during high-intensity activities. short sharp bursts of activity
Why does a marathon runner not rely so much on the Cori cycle?
Muscles are burning fuel aerobically. Running at slower pace, so good supply of oxygen to the muscles.
