Glycogen Metabolism in Muscle and Liver Flashcards
What is glycogen and where is it normally stored?
- storage form of polysaccharides
- liver and skeletal muscle
What is the main role of liver glycogen in the body?
- maintain plasma glucose levels between meals
- done through glycogenolysis
Is glycogenolysis catabolic (breaking down) or anabolic (building things up)?
- catabolic
- Exergonic = energy Exits the reaction
- provide energy for anabolic reactions (coupling)
What is the main role of skeletal muscle glycogen in the body?
- maintain muscle contraction
- glucose broken down in skeletal muscle stays in skeletal muscles
What is glycogenesis?
- glycogen is formed from dietary glucose
Glucose is a highly branched polysaccharide of glucose consisting of α1-4 linked glucose molecules with an α1-6 branch every 8-14 glucose residues. Why is this important?
- provides a large number of ends at which phosphorylase and glycogen synthase can act to ensure rapid breakdown and re-synthesis
In a highly branched polysaccharide of glucose consisting what does α1-4 and α1-6 linked glucose molecules mean?
α1-4 - glucose molecules are linked at 1 and 4 carbons
α1-6 - glucose molecules are linked at 1 and 4 carbons
What is the role of phosphorylase and glycogen synthase with glucose?
- phosphorylase = breaks down and removes glucose = Glycogenolysis
- glycogen synthase = adds glucose to glucose chains = Glycogenesis
What % of the liver and skeletal muscle weight is glycogen storage in the fed state?
- liver = 10%
- skeletal muscle = 2%
- BUT more glycogen is stored in the muscle as there is more total skeletal muscle mass in the body
In the image below what do the numbers 1 and 2 denote in terms of a1-4 and a1-6 glucose bonds?
- 1 = a1-4
- 2 = a1-6
In times of metabolic need glycogen is broken down, often called mobilisation. Glycogen is broken down into glucose 1 phosphate (phosphate group is attached to carbon 1) and then it can be reversibly broken down into glucose 6 phosphate (phosphate group is attached to carbon 6). What enzyme is responsible for this and what happens to the molecule when converting it from glucose 1 phosphate into glucose 6 phosphate?
- phosphoglucomutase
- moves the phosphate group from carbon 1 to carbon 6
In times of metabolic need glycogen is broken down, often called mobilisation. Glycogen is broken down into glucose 1 phosphate (phosphate group is attached to carbon 1) and then it can be reversibly broken down into glucose 6 phosphate (phosphate group is attached to carbon 6). Phosphoglucomutase is responsible for this and moves the phosphate group from carbon 1 to carbon 6. Why is this important in ATP generation?
- glucose 6 phosphate is the 1st stage of glycolysis
- so glycogen breakdown can initiate glycolysis
In times of metabolic need glycogen is broken down, often called mobilisation. Glycogen is broken down into glucose 1 phosphate (phosphate group is attached to carbon 1) and then it can be reversibly broken down into glucose 6 phosphate (phosphate group is attached to carbon 6). Phosphoglucomutase is responsible for this and moves the phosphate group from carbon 1 to carbon 6. Why is glucose 6 phosphate important in glycogen breakdown in the liver?
- glucose 6 phosphotase can remove phosphate and glucose can be pumped into the blood plasma
- important for maintaining blood glucose levels
In the liver glycogen can be broken down into glucose 1 phosphate (G-1-P) (phosphate group is attached to carbon 1) and then it can be reversibly broken down into glucose 6 phosphate (G-6-P) (phosphate group is attached to carbon 6). This means it can provide energy to glycolysis (G-6-P) and help maintain blood glucose levels (G-1-P). Does skeletal muscle produce G-6-P and G-1-P?
- no only G-6-P
- goes straight into energy metabolism
The liver is able to provide energy from glycogen that enters glycolysis, but importantly can also contribute to plasma glucose levels. To do this glucose-6-phosphate can be phosphorylised straight into glucose and enter the blood. What enzyme facilites this in the liver?
- glucose 6-phosphatase (removes phosphate)
- reverse of hexokinase (adds phosphate)
If fasting continues overnight, how long would our liver glycogen stores generally last?
- 12-24 hours
PHOSPHOROLYSIS is the process of breaking down α1-4 linkages in glycogen. What enzyme is responsible for this, and what is formed when a single unit of glycogen is broken off?
- glycogen phosphorylase breaks the bonds in glycogen by adding a phosphate to the glucose molecule
- glucose-1-phosphate is formed
PHOSPHOROLYSIS is the process of breaking down α1-4 linkages in glycogen. GLYCOGEN PHOSPHORYLASE is responsible for this. Does it break off big chunks of the glycogen or does it nibble off and take 1 glucose molecule at a time?
- 1 molecule at a time
- but due to structure of glycogen phosphorylase can act on multiple ends, releasing multiple glucose
Is glycogen phosphorylase able to break down both α1-4 and α1-6 bonds of glycogen?
- no
- only α1-4 bonds
Glycogen phosphorylase is only able to break down α1-4 bonds of glycogen. In the second phase of glycogenolysis (breaking down glycogen) another enzyme is required to break the branches of the α1-6 bonds of glycogen. What is this enzyme called?
- de-branching enzyme
Glycogen phosphorylase is only able to break down α1-4 bonds of glycogen. Glycogen phosphorylase is also unable to break down any α1-4 bonds when it is within how many bonds from a α1-6 bond?
- 4 bonds (inlcuding the α1-6 bond)
Glycogen phosphorylase is only able to break down α1-4 bonds of glycogen. Glycogen phosphorylase is also unable to break down any α1-4 bonds which are within 4 bonds from a α1-6 bond. The de-branching enzyne is able to do what with 3 of the α1-4 bonds before the α1-6 bind?
- the 3 of the α1-4 bonds are moved to the non-reducing end of the chain
Once the de-branching enzyme has removed 3 of the α1-4 bonds and moved them to the non-reducing end of the chain. What does the de-branching enzyme do to the α1-6 bond?
- hydrolyses the α1-6 bond using water
- instead of becoming glucose-1-phosphate, this molecule becomes glucose as no phosphate
What are the 2 enzymes involves in breaking down glycogen and which breaks down the a1-4 and a1-6 bonds?
1 - glycogen phosphorylase = a1-4 bonds
2 - debranching enzyme = a1-6 bonds
In glycogen synthesis glucose is converted into what, and what enzyme is responsible for this?
- ATP used to create glucose-6-phosphate is created
- hexokinase or glucokinase in the liver
In glycogen synthesis glucose is converted into glucose-6-phosphate by hexokinase or glucokinase in the liver. Instead of entering the glycolysis pathway, what is it converted into and what enzyme is responsible for this?
- glucose-1-phosphate
- phosphoglucomutase moves phosphate from 6th ro 1st carbon
In glycogen synthesis glucose is converted into glucose-6-phosphate by hexokinase or glucokinase in the liver. Instead of entering the glycolysis pathway, it is converted into glucose-1-phosphate (G-1-P) by phosphoglucomutase moving phosphate from 6th ro 1st carbon. What then happens to (G-1-P)?
- it is activated by adding a nucleotide called uridine triphosphate
- this creates uridine diphosphate glucose (UDP-glucose)
In glycogen synthesis glucose is converted into glucose-6-phosphate by hexokinase or glucokinase in the liver. Instead of entering the glycolysis pathway, it is converted into glucose-1-phosphate (G-1-P) by phosphoglucomutase moving phosphate from 6th ro 1st carbon. The G-1-P is then activated by adding a nucleotide called uridine triphosphate, creating uridine diphosphate glucose (UDP-glucose). What then happens to UDP-glucose?
- glucose synthase adds UDP-glucose to an end of glycogen forming an a1-4 bond
- the UDP is removed
What bonds does glycogen synthase make in the synthesis of glycogen?
- α1-4 bonds
Glycogenin is a glycogen primer, how is it involved in glycogen synthesis?
- uridine diphosphate ias added to glucose (UDP-glucose)
- UDP-glucose attaches to glycogen primer
- additional glucose molecules are added to the primer, once 4 glycogen are present glycogen synthase can take over
Glycogen synthase is able to add to chains of glycogen, but only at the a1-4 bonds. What enzyme is responsible for adding braches to the glycogen bonds?
- branching enzyme
Glycogen synthase is able to add to chains of glycogen, but only at the a1-4 bonds. Branching enzyme is responsible for adding braches to the glycogen bonds. How does it do this?
- takes 7 glycogen molecules from the end of the a1-4 bond chain
- forms a1-6 bond ansd attaches to the a1-4 chains
- BUT must be 4 glycogen molecules from another a1-6 bond
- we now have chains and braches
Which 2 enzymes are responsible for making a1-4 and a1-6 bonds in glycogen synthesis?
- a1-6 bonds = branching enzyme
- a1-4 bonds = glycogen synthase
Which 2 enzymes are responsible for breaking a1-4 and a1-6 bonds to facilitate glycogenolysis (breaking down of glycogen)?
- a1-4 = Glycogen phosphorylase
- a1-6 = Debranching enzyme
What enzyme is responsible for the reversible conversion of glucose-1-phosphate and glucose-6-phosphate?
- phosphoglucomutase
Glycogen is a good energy store as it can be mobilised quickly into energy. However, if glycogen is so good, why do we not store more energy is glycogen?
- glucose is hydrophilic
- glucose will therefore attract H2O and increase weight and bulk
- this is why when we fast weight can change as glycogen stores drop as does H2O
In what situations is glycogen mobilisation increased?
- in the liver during starvation,
- glucose is required for glycolysis by the brain and RBCs
- high muscle muscle demand to fuel glycolysis during exercise
In what situations is glycogen synthesis increased?
- replenish liver glycogen following feeding (insulin involved)
- replenish muscle stores when exercise stops (insulin involved)
Does glycogen synthesis or glycogen breakdown require energy?
- glycogen synthesis
What is allosteric binding on an enzyme?
- when a molecule binds to an enzyme, but not the active site
- this is able to control enzyme activity
Glycogen phosphorylase is the enzyme that breaks down glycogen at the a1-4 bonds. If ATP is low in skeletal muscle, what happens to glycogen phosphorylase?
- adenosine monophosphate (AMP) allosterically binds to glycogen phosphorylase
- glycogen phosphorylase is turned on and increase glycogen breakdown
Glycogen phosphorylase is the enzyme that breaks down glycogen at the a1-4 bonds. If ATP is low in skeletal muscle, what happens to glycogen phosphorylase?
- adenosine monophosphate (AMP) allosterically binds to glycogen phosphorylase
- glycogen phosphorylase is turned on an increases glycogen breakdown
Glycogen sythase is the enzyme that builds glycogen at the a1-4 bonds. If ATP and glucose-6-phosphate (G-6-P) is high in the skeletal muscle, what happens to glycogen synthase?
- ATP and G-6-P can allosterically binds to glycogen synthase
- glycogen synthase is activated and increases glycogen synthesis
What happens to glycogen phosphorylase and glycogen synthase when ATP and glucose-6-phosphate (G-6-P) are high or low?
- high ATP/G-6-P = increased glycogen synthase (build glycogen)
decreased glycogen phosphorylase (break glycogen)
- low ATP/G-6-P = decreased glycogen synthase (build glycogen)
increased glycogen phosphorylase (break glycogen)
What are cells programmed to do if the input to glycolysis (glucose 6-phosphate), and the product of glycolysis (ATP) are present in high abundance in the cell?
- store glucose as glycogen
What is the name of enzymes that adds a phosphate group to a molecule?
- protein kinases and phosphorylase
- process of adding a phosphate is called phosphorylation
What is the name of enzymes that remove a phosphate group to a molecule?
- protein phosphatases
- process of removing a phosphate is called dephosphorylation
- rememeber tase sounds like taking off
Are enzymes that contain or do not contain a phosphate more active?
- contains a phosphate are more active
- phosphorylation increases enzyme activity
Glycogen Phosphorylase, which is responsible for the breakdown of glycogen is activated by cAMP-dependent phosphorylation. Hormones such as glucagon and adrenalin are able to initiate which enzyme, and what does this enzyme then do?
- adenylyl cyclase
- converting ATP into cAMP
- increases glycogen phosphorylase activity
Glycogen Phosphorylase, which is responsible for the breakdown of glycogen, is activated by cAMP-dependent phosphorylation. This is facilitated by hormones such as glucagon and adrenalin that are able to activate adenylyl cyclase which then converts ATP into cAMP and increases glycogen phosphorylase activity. However, what effect does cAMP cascade have on the glycogen synthase do?
- protein kinase phosphorylates glycogen synthase, converting the enzyme to the ‘b’ (less active) conformation
- glycogen synthase activity is therefore reduced when protein kinase is activated
What happens to the activity glycogen synthase and glycogen phosphorylase when hormones such as glycogen and adrenaline activate cAMP and protein kinase A (pKA), meaning they undergo phosphorylation?
- glycogen synthase decrease when pKA is active
- glycogen phosphorylase increases when pKA is active
- BOTH favour glycogen breakdown
What happens to the activity glycogen synthase and glycogen phosphorylase when hormones such as glucagon and adrenaline do not activate cAMP and protein kinase A (pKA), meaning they do not undergo phosphorylation?
- glycogen synthase increase when pKA is inactive
- glycogen phosphorylase decreases when pKA is inactive
- BOTH favour glycogen sythesis
What is the most common cause of glycogen storage disorders?
- mutations in gene encoding individual enzymes in the glycogen metabolism pathway
- clinical presentation is variable depending on tissue affected
In glycogen storage disorders how do liver glycogen storage disorders present?
- with fasting hypoglycaemia
- hepatomegaly (enlarged liver)
In glycogen storage disorders how do skeletal muscle glycogen storage disorders present?
- exercise intolerance and rhabdomyolysis (muscle cell death and release of cell contents)
- fixed muscle weakness without rhabdomyolysis
What is Von Gierke disease?
- mutation in glucose-6-phosphates enzyme
- phosphate group cannot be removed
- therefore glucose can not enter plasma as glucose from the liver
Von Gierke disease is caused by a mutation in the glucose-6-phosphates enzyme. Here the phosphate group cannot be removed and glucose can not enter plasma as glucose. What can this do to other pathways?
- increased pentose phosphate pathway
- increased glycolysis
- increased lipogenesis
