Glycogen Breakdown Flashcards
Go through the steps our body goes through to increase out glucose levels in fasting state
- Glucose is converted into pyruvate
- Pyruvate converted into acetyl CoA
- Acetyl CoA enters the citric acid cycle
- Citric acid cycle produces high energy electrons that go to the electron transport chain
How is glucose stored?
Stored as glycogen in our muscles and liver
When is liver glucose released?
- Can be released into the blood during fasting
2. During fight or flight liver can metabolise glycogen stored and releases glucose for use by muscle
Does the liver use the stored glycogen for fuel?
no it can use glycogen derived glucose for the pentose phosphate pathway
What happen when prolonged fasting occurs?
Glycogen reserves will be used up and metabolism needs to start synthesising glucose from non-carbohydrates to maintain blood glucose levels (gluconeogenesis)
What is gluconeogenesis
The synthesis of glucose from non carbohydrate sources
Why is glucose important ?
- AS it is the only energy source used by the brain and is required by cells with no mitochondria
- It is the energy source for exercising muscles and is the substrate for anaerobic glycolysis
Why has the body developed mechanisms for storage and supply of glucose?
As dietary intake of glucose is sporadic and not always reliable
Between meal and during exercise where do we get glucose from?
From glycogen when it’s metabolised
Name the main stores of glycogen
Muscles
Liver
What is the molecular mass of one glycogen molecule
Can be up to 10^8 (100,000,000)
How does glycogen exist?
Exists as discrete cytoplasmic granules which contain most of the enzymes necessary for glycogen synthesis and degradation
Describe the structure of glycogen
- it is a homopolysaccharide made form only alpha D glucose
- Made up of multiple chains
- Is highly branches
Name the bond that links each unit of glycogen
Glycosidic bond
What type of glycosidic bond is present in glycogen?
Alpha 1,4 link between each unit
Alpha 1,6 link at branch points
When does Glycogen branching occur?
Occurs every 8-10 glucosyl residues
What does the alpha stand for in the alpha 1,6 AND 1,4 LINKS
Means theres the same stereochemistry between both glycogen been combines
What is the significance of branching?
Branching creates countless non reducing ends which means glycogen can be synthesised or broken down rapidly
What is the difference between glycogen and starch
Starch is not as branched
How is glycogen synthesised and broken down?
By adding or removing glucose units from non reducing ends
What is the main function of liver glycogen
To maintain blood glued between meals and during early stages of fasting
What is the main function of muscle glucose
It isa fuel reserve for muscle contraction
Is the glucose released from LIVER glycogen exportable?
Yes as it is released from the lover into the blood stream to be used by other tissues
Is the glucose released from muscle glycogen exportable?
No as this glucose cannot leave the muscle
How big is the glycogen store in the liver
10% wet weight of liver
How long does the glycogen stored in the liver last?
Around 24 hours during fasting
How big is the glycogen store in the muscles
1-2% of wet weight of muscles
Name the hormones that promote the breakdown of liver glycogen
Glucagon and adrenaline
Name the hormones that promote the breakdown of liver glycogen
Adrenaline
Name the hormone that promotes synthesis os glycogen
insulin
When is liver glycogen broken down from non reducing terminals?
- When blood glucose levels begin to fall
2. When musclesneed glucose for ATP production
Is more glycogen stored in the liver or in muscles?
Muscles a we have more muscles than liver
When is muscle glycogen broken down from non reducing terminals?
When musclesneed glucose for ATP production
State the chemical formula for the break down of glycogen
Glycogen + Pi -> Glucose 1 phosphate +Glycogen (in 1 less residue)
Name the enzyme that aids glycogen breakdown
Glycogen phosphorylase
What does glycogen break down release?
Glucose 1-phophate not free glucose
Describe phosphorylated glucose
Phosphorylated glucose is a more “energy rich” molecule than glucose.
When does glycogen phosphorylate stop cleaving
When it gets to within 4 resides of a branch point
What happens when glycogen phosphorylase hits a branch point?
It stops cleaving
Name the 2 additional enzymes required to break down glycogen at a branch point
- Transferase
2. Hydrolase
Talk through the break down of glycogen at a branch point
- Glycogen phosphorylase Stops cleaving 4 residues from a branch point
- Transferase enzyme transfers 3 glucose unit to end of glycogen molecule
- Hydrolase Enzyme hydrolyses the single glucose unit left behind
State the ratio between glucose 1-phosphate production and glucose production during glycogen breakdown
8:1
How do we use glucose 1-phosphate in the liver?
- First we convert it into glucose 6-phosphate via enzyme Phosphoglucomutase
- Then glucose 6-phosphate is converted into glucose via enzyme Glucose 6-phosphatase
- Glucose is then released into the blood to maintain blood glucose levels
What does Phosphoglucomutase do?
Converts glucose 1-phosphate into glucose 6-phospahte
What does Glucose 6-phosphatase do
Converts Glucose 6-phosphate into glucose
Name the enzyme that might be defected in patients suffering from type 1 diabetes
Glucose 6-phosphatase
How do we use glucose 1-phosphate in our muscles ?
- First we convert it into glucose 6-phosphate via enzyme Phosphoglucomutase
- glucose 6-phosphate is then trapped in the muscles cell for use in glycolysis
Why isn’t glucose 6-phosphate converted into glucose in muscle cells
As muscles don’t have the glucose 6-phosphatase enzyme
How is glucose used in the muscles?
It is converted into glucose 6-phosphate via hexokinase then used for glycolysis
What does hexokinase do?
Converts glucose into glucose 6-phosphate
When do we need to synthesis glycogen?
When we have a surplus of glucose (usually after a meal)
How is glycogen metabolism regulated?
- By hormones
2. Allosteric Control regulates glycogen metabolism
What does adrenaline do in muscles?
It stimulates muscle glycogen breakdown
What does adrenaline do in the liver?
stimulate glycogen breakdown in the liver.
What does glucagon do in the liver?
stimulate glycogen breakdown in the liver.
Talk through the stages of hormonal control of glycogen breakdown
- Adrenaline and glucagon receptors activate adenylate
cyclase - This adenylate
cyclase catalyses the formation of cAMP - cAMP activated Protein kinase A
Protein kinase does 2 thing:
A. The catalytic side of Protein kinase A activates Phosphorylase kinase. This activates Phosphorylase kinase which in turn breaks down glycogen
B. The regulator side of Phosphorylase kinase inhibits glycogen synthase so Glycogen synthesis
switched off
What does cAMP do to stimulate glycogen breakdown?
cAMP activated Protein kinase A
What does protein kinase A do?
- The catalytic side of Protein kinase A activates Phosphorylase kinase. This activates Phosphorylase kinase which in turn breaks down glycogen
- The regulator side of Phosphorylase kinase inhibits glycogen synthase so Glycogen synthesis
switched off
What does insulin do to regulate glycogen metabolism?
Insulin is released when blood glucose levels are elevated and stimulates glycogen synthesis whilst inhibiting breakdown.
What is the hormone control of glycogen break down known as
The Amplification cascade
Talk through the stages of hormonal control of glycogen synthesis
- Insulin receptor (Tyrosine kinase) activates protein kinase
- Protein kinase activates Phosphoprotein
phosphatase 1 - Phosphoprotein
phosphatase 1 does 2 things:
A, It inhibits Glycogen
phosphorylase b so glycogen break down is switched off
B. It activates Glycogen
synthase a so glycogen synthesis occurs
Name the 5 main glycogen stage disease
- Von Gierke’s disease
- Pompe’s disease
- Forbes’ disease
- Andersen disease
- McArdle disease
What does the Von Gierke’s disease affect?
Affects the Liver, intestines and kidneys
Glucose 6-phosphatase is defected
What does the Pompe’s disease affect?
Affects the liver, muscles and heart
Lysosomal Alpha glucosidase is inhibited
What does the Forbes’ disease affect?
Affects the liver and muscles
Leads to an abnormal glycogen structure
The Amylo-1-6- glucosidase is defected
What does the Andersen disease affect?
Affects the liver and muscles
Leads to an abnormal glycogen structure
The 1- 4- glucan branching enzyme is defected
What does the McArdle disease affect?
Affects muscles only
The phosphorylase enzyme is defected
What is the outcome of the Von Gierke’s disease
If the patent survives the initial hypoglycaemia then prognosis is good
Hyperuricaemia is a late complication
What is the outcome of the Pompe’s disease
Death in the first 6 months
What is the outcome of the Forbes’ disease
Good prognosis
What is the outcome of the Andersen disease
Death in first 3 years
What is the outcome of the McArdle disease
Normal lifespan but exercise must be avoided
Whta is non alcoholic steato hepatitis?
It can be defined as the liver manifestation
of a metabolic disorder, and is the most severe
form of non-alcoholic fatty liver disease
