Glycogen Metabolism Flashcards
Glycogen and epinephrine have ____ effects on glycogen synthase activity
negative
Role of glycogen in muscle/most tissues
storage form of glucose that ultimately is used to generate ATP inside cell
Role of glycogen in liver
Breaks down glycogen and serves as a source of glucose for other tissues by Glucose 6 phosphatase
How does glycogen stores change in the liver from well-fed to starvation
Well fed state - high
24 h starvation - low because it have been breaking down to release glucose
What is the structure of gluycogen
- It is the storage form of glucose in animal cells.
- It is a polymer of glucose containing a-1,4 glyosidic bonds and a-1,6 bonds at branch points
- Glycogen allows large amounts of glucose to be stored in the cell because of branch points
How is Glycogen synthesized?
- When glucose is taken up into a liver cell, its converted to G-6-P which is converted to G-1-P
- G-1-P is converted to UDP-glucose which is the immediate donor of glucose residues to glycogen
- The degradation products of glycogen are G-1-P and glucose
How is Glycogen degraded?
- In degradation, glycogen is broken down to G-1-P and glucose
G-1-P can be converted to G-6-P since the liver has G-6-Pase, the phosphate is removed and glucose can leave - In muscle cell, the G-6-P is not dephosphorylated, but will enter glycolysis
What is glycogenesis
- synthesis of glycogen from glucose
- Initial steps involve a protein, glycogenin (which is a primer and an enzyme)
- Glycogenin catalyzes the transfer of glucose residues from UDP glucose and keeps adding on UDP-glucose residues to form a glycogen primer
after that glycogen synthase will add on to the primer and branching enzyme will make branches
How does UDP-glucose acts as glucose donor for glycogen
- The negatively charged phosphate in G-1-P attacks the alpha-phosphate of UTP
- Pyrophosphate (PPi) is displaced
- Hydrolysis of PPi drives the reaction forward
- The high energy bond in UDP-glucose favors incorporation of glucose to glycogen
Explain the process of glycogen synthesis
Glycogen synthase elongates an already existing glycogen chain which was made my glocogenin
- the substrate for glycogen synthase are glycogen and UDP-glucose
- glucose from UDP-glucose is transferred from the non-reducing end of glycogen chain
- the glycogen chain is increased by 1 glucose with a new a-1,4-glycosidic linkage by glycogen synthase
- the synthase adds glucose residues until the chain reaches a certain length
- glycogen synthase can’t form the a-1,6 glycosidic linages
- the branching enzyme cleaves a 6-9 unit of glucosyl residues and forms an a-1,6-glycosidic bond with a glucosyl residue in the glycogen core
What is the rate limiting step in glycogen synthesis
glycogen synthase
UDP-glucose –> UDP
How is glycogenesis regulated?
glycogen synthase catalyzes the rate limiting step
- glucagon (liver) and epinephrine (liver and muscle) have negative effects on glycogen synthase activity
- insulin causes an increase in glycogen synthase activity
Which is the active and inactive form of glycogen synthase?
Inactive - phosphorylated
active - no phosphate group (de-phosphorylation)
Glucagon/epinephrine favour the _____ form of glycogen synthase
inactive
Insulin favors the ____ form of glycogen synthase
active
How is glycogen synthase phosphorylated?
The phosphorylation is initiated by cAMP-depended protein kinase A
What is glycogenolysis?
The breakdown of glycogen into glucose
What is glycogen degraded to?
What happens to the product?
Glycogen is degraded into glucose 1-P and glucose
Glucose-1-P is converted to glucose-6-P for entry into other pathways
How is glycogen degraded?
By 2 enzymes:
- Glycogen phosphorylase - - breaks the a-1,4-glycosidic bonds by using a phosphate ion as a nucleophile and releasing G-1-P
- if water was used to break the bond, we would get glucose which would leave the cell. With phosphate, the phosphate is kept and cant leave the cell
- Glycogen phosphorylase cannot degrade glucosyl residues near the branch point - The debrancher enzyme
- transferase activity - removes the glucosyl residues and adds it to a longer chain through a-1,4, glycosidic bond
- a-1,6-glucosidase activity - hydrolyzes the a,1-6-glycosidic bond to release glucose by adding water
Which enzyme catalyzes the rate limited step in glycogen-degradation?
Glycogen phosphorylase
What is the major and minor product of glycogen degradation?
major - Glucose-1-phosphate
minor - glucose
The degradation of glycogen normally produces which of the following?
A. More glucose than glucose-1-phosphate B. More glucose-1-phosphate than glucose C. Equal amounts of glucose and glucose-1-phosphate D. Only glucose-1-phosphate E. Only glucose
B. More glucose-1-phosphate than glucose
How is glycogenolysis regulated?
- Glycogen phosphorylase catalyzes the rate-limiting step.
- Glucagon (liver) and epinephrine (liver and muscle) have positive effects on glycogen phosphorylase activity
- Insulin causes a decrease in glycogen phosphorylase activity
How is glycogen metabolism regulated in the liver in the fed state
- we have insulin present
- it will activate glycogen synthase
- inhibit glycogen phosphorylase