Glycogen Metabolism I Flashcards
What is the structure of glycogen?
A long chain homopolymer of glucose molecules with branches.
How are glucose molecules that compose glycogen linked together?
Linear chains are connected via alpha- 1,4 glycosidic bonds
Branched chains are connected via alpha- 1,6 glycosidic bonds
Describe the ends of glycogen chains
Made up of non-reducing ends that contain terminal glucose with an exposed hydroxyl group at Carbon 4
What is the purpose of glycogenin?
The reducing ends connect to this
Serves as a primer for glycogen synthesis
Glycogen is degraded and extended from the ____ ____ _____
Non-reducing end
Where is glycogen stored?
In the liver and muscles
What is glycogen stored as?
Granules
What are the 2 functions of glycogen?
Liver glycogen- regulates blood glucose levels
Muscle glycogen- provides a reservoir of fuel (glucose) for physical activity
What is the purpose of glycogen metabolism?
To regulate storage and release of glucose
What are the 3 regulation mechanisms of glycogen?
Allosteric control
Covalent modification- through reversible phosphorylation of key enzymes
Hormonal control
What are the 3 key steps of glycogenesis?
Explain the first key step.
- Trapping and activating glucose
- Elongation of glycogen primer
- Branching of glycogen chains
- Trapping and activation of glucose- Glucokinase/Hexokinase catalyzes glucose to G6P
- Phosphoglucomutase then reversibly isomerizes G6P to G1P
- G1P is converted into UDP-Glucose via Uridine diphosphate (UDP)-Glucose Phosphorylase. Note UDP-Glucose is the active form of Glucose
What enzyme catalyzes G1P to UDP-Glucose?
UDP-Glucose Phosphorylase
What is the rate-limiting enzyme in glycogenesis?
Glycogen Synthase- catalyzes the transfer of glucose from UDP- glucose to the non-reducing end of the glycogen chain. Forms alpha- 1,4 glycosidic bonds between glucose molecules
What enzyme catalyzes the branching of glycogen?
Glucosyl (4:6) Transferase
Describe the process of glycogen branching.
When the glycogen chain reaches 11 residues, a fragment of the chain (about 7 residues long) is broken off at an alpha- 1,4 link and reattached elsewhere through an alpha- 1,6 link by Glucosyl (4:6) Transferase
The new branch point must be at least ___ residues away from the preexisting branch.
4
What is the purpose of glycogen branching?
Increases solubility of glycogen
Increases the number of terminal non-reducing ends
Increases rate at which glycogen can be synthesized and degraded
What are the enzymes that catalyze the branching of glycogen?
alpha- 1,4 linkage adds glucose polymers by UDP-glucose and Glycogen Synthase (1 non-reducing ends)
Long glucose polymer branches via Glucosyl (4:6) Transferase to catalyze the alpha (1,6)- linkage (2 non-reducing ends)
Describe the steps of glycogenesis.
Glucose to G6P via Hexokinase/Glucokinase
G6P to G1P via Phosphoglucomutase (PGM)
G1P to UDP-Glucose via UDP-glucose pyrophosphorylase
UDP-Glucose to linear Glycogen via Glycogen Synthase (GS)- rate limiting steps
Linear Glycogen to branched glycogen via Glucosyl (4:6) Transferase
What is the first step of glycogenolysis?
Glycogen break down to release glucose-1 Phosphate
What are the 4 key enzymes of glycogenolysis and their functions?
Glycogen Phosphorylase -Catalyzes the cleavage of glycogen (causes linear chain shortening at the non-reducing end)
Phosphoglucomutase -Two to Remodel glycogen remnants (one for the liver and one for muscle)
Glucose 6 Phosphatase -Converts glycogen breakdown product suitable for metabolism
What is the rate-limiting enzyme of glycogenolysis?
Glycogen Phosphorylase
Glycogen phosphorylase add an ________ and releases a glucose residue as glucose-1 phosphate
Orthophosphate (PO4^3-)
Glycogen phosphorylase uses _____ ____ (AKA ______ ___) as a cofactor
Pyridoxal Phosphate
Vitamin B6
Phosphorolysis of glucose residues continues till the Glycogen Phosphorylase gets within _ ____ of the _____ _____ of a branch point.
4 residues
Alpha- 1,6 linkage
Once G1P is released from the linear chain glycogen what catalyzes G1P to G6P?
Phosphoglucomutase
Glycogen at this point has 4 glucose molecules attached/branched to a long glucose polymer underneath it. What enzyme catalyzes the release of 3/4 of the glucose molecules on the top strand and adds them to the bottom strand in a linear fashion?
Transferase
What enzyme catalyzes the release of the last glucose molecule attached to the linear chain in a branched fashion?
Alpha- 1,6 Glucosidase
What is the overall yield of debranching of glycogen?
10 G1P for every 1 glucose
the 1 glucose is always the last glucose monomer in the branched chain to be released
Can G6P leave the cell?
No! Glucose 6 Phosphate cannot leave the cell. It must first be converted to glucose and then leave.
T1- Pulls G6P into the cell
T2- Rips phosphate off G6P via G6P phosphatase
T3- Pushes glucose out of the cell
Which one, the liver or muscle cells, has Glucose 6 Phosphatase?
Liver, converts it to glucose which can be released into the bloodstream
Muscle cells do not have glucose 6 phosphatase so G6P stays in the cells
Describe lysosomal glycogenolysis. What enzyme is used to catalyze this reaction?
A small amount of glycogenolysis occurs via lysosomal alpha 1,6 glucosidase (AKA acid maltase).
Shortens branches of glycogen but does not debranch them.
Causes the release of free glucose
What is Pompe Disease?
When you do not have sufficient levels of alpha- glucosidase (AKA acid maltase)
What is Von Gierke Disease?
Deficiency in Glucose 6 Phosphatase levels, therefore leading to the inability to form free glucose from G6P in the liver
During glycogenolysis, G6P is found in both the liver and muscle, but what is the difference when they are in their respective locations?
G6P in the liver is able to become free glucose via glucose 6 phosphatase
G6P in muscle can be directly used in glycolysis to form energy for active muscles
During glycogenolysis, G1P cannot enter what 2 tissue types and must be converted into what to enter these tissues?
Liver and Muscle
G6P via Phosphoglucomutase
What is Hers Disease?
The inability to form G1P (for the liver) from Glycogen due to a deficiency in Glycogen Phosphorylase
What is McArdle Disease?
The inability to form G1P (for muscles) from Glycogen due to a deficiency in Glycogen Phosphorylase
What is Cori Disease?
The inability to release the last glucose molecule attached in a branched fashion to the linear chain below it.
Due to the deficiency of the debranching enzyme alpha 1,6- Glucosidase
This causes a buildup of glycogen to form.
