Glycogen Metabolism Flashcards
(43 cards)
What is glycogen
The storage form of glucose
Where is glycogen found
Liver and muscles
How is glycogen stored differently in the liver vs. the muscles?
Glycogen = stored in granules
- Muscles: glycogen is stored in beta granules
- Liver: beta granules combine to form alpha granules (10-15 beta granules)
Why is having glycogen beneficial to vertebrate organisms?
Some tissues (ex: brain) are in need of a constant supply of glucose. The compact structure of glycogen granules allows for glucose to easily be stored when there is excess and made available at a short notice.
Describe the structure of glycogen
- In the center there is a glycogenin homodimer surrounded by tiers of chains of about 13 glucose residues
- Inner B-chains contain two branch points
- Outer A-chains are unbranched (make up the majority of the granule)
- Reducing end: anomeric carbon (number 1 position)
- Non-reducing end (number 4 carbon)
What creates the branched structure of glycogen?
(α1→6) linkages
These linkages contribute to the branched structure of B chains
What linkages are responsible for conecting the A and B chains of glycogen?
(α1→4) linkages
What 3 enzymes are important for the breakdown of glycogen (glycogenolysis)?
- Glycogen phosphorylase
- Glycogen debranching enzyme
- Phosphoglucomutase
Describe the first step of glycogenolysis
Glycogen phosphorylase uses phosphate to convert glucose to glucose 1-phosphate breaking bonds between glucose residues at the (α1→4) linkage leaving behind another non-reducing end
When will glycogen phosphorylase stop?
When there are 4 glucose molecules left on the glycogen chain
Describe the regulation of glycogen phosphorylase
- 2 forms
- Phosphorylase B: dephosphorylated (inactive)
- Phosphorylase A: phosphorylated (active)
What is the role of phosphorylase kinase B
Regulates the activation of glycogen phosphorylase into its A form
What is the role of phosphoprotein phosphatase 1 (PP1)
Regulates the deactivation of glycogen phosphorylase into its B form
Describe the hormonal regulation of Phosphorylase B kinase
- Glucagon (liver) and epinephrin (muscle) act on GPCR’s located on the surface of the cell
- Once the receptor is activated GS-alpha subunit is activated
- GS-alpha subunit converts ATP into cyclic AMP thus raising the concentration
What role does cyclic AMP play in the hormonal regulation of phosphorylase B kinase
- Cyclic AMP activates protein kinase A which allosterically activates phosphorylase B kinase
- Phosphorylase kinase B activates glycogen phosphorylase into its A form (active)
- Glycogen breakdown is stimulated
The hormonal regulation of phosphorylase B kinase is an example of what?
Ań enzymatic cascade
Initiated by epinephrin or glucagon
Describe the allosteric regulation of glycogen phosphorylase by glucose
- Glycogen phosphorylase is a glucose sensor
- 2 allosteric sites separate from the active site will bind to glucose molecules at certain concentrations
- Glycogen phosphorylase undergoes a conformational change when glucose binds to its allosteric sites (serine residues stick out making it easier to remove phosphate groups)
- When blood glucose is low glucagon / epinephrin initiate cascade mechanism that activates glycogen phosphorylase to A form (glucose = released into the blood)
- When blood glucose is high glucose binds to inhibitory allosteric sites on glycogen phosphorylase A resulting in PP1 catalyzing the dephosphorylation of glycogen phosphorylase A into its inactive B form
Describe the second step of glycogenolysis
- The debranching enzyme (oligo (α1→6) to (α1→4) glucantransferase) catalyzes 2 successive reactions
- Transferase activity shifts three glucose residues from the branch of one chain to the nonreducing end of another chain (elongation)
- There is one single glucose residue remaining at the branch point
- The (α1→6) glucosidase activity of the debranching enzyme releases the remaining glucose residue
- The remaining unbranched (α1→4) polymer is now ready for further phosphorylation by glycogen phosphorylase
Describe the third step of glucogenolysis
Phosphoglucomutase converts glucose 1-phosphate to glucose 6-phosphate
What role does serine play in the third step of glucogenolysis?
- The serine residue located at the active site of phosphoglucomutase is what is initially phosphorylated
- The phosphate group is transferred from the number 1 position to the number 6 position leaving you with glucose 6-phosphate
How does the use of glucose 6-phosphate differ between the muscle and liver?
Muscle: glucose 6-phosphate enters glycolysis
Liver: glucose 6-phosphate enters the ER reticulum where it can be released into the bloodstream when blood glucose levels drop
Describe how glucose 6-phosphate is released into the blood stream by the liver when glucose levels drop
- Requires glucose 6-phosphatase (only present in the liver and kidney)
- Glucose 6-phosphatase = located on the endoplasmic reticulum with its active site on the lumen side of the ER
- Glucose 6-phosphate formed in the cytosol enters the ER lumen through G6P transporter (T1)
- In the lumen, the active site of glucose 6-phosphatase will remove the phosphate group from glucose
- Glucose is then transported from the lumen back into the cytosol (by transporters T2 and T3)
- Glucose can then enter the bloodstream via the plasma membrane transporter GLUT2
Describe glycogenesis by UDP glucose
- The generation of glycogen from individual glucose molecules requires UDP glucose (a sugar nucleotide)
- Anomeric carbon of the sugar is activated by attachment to a nucleotide through a phosphate ester linkage
- UDP glucose and other sugar nucleotides = important in glycogen synthesis and other carbohydrate derivatives (ex: monosaccharides, disaccharides etc)
Why is UDP glucose important?
- Easy to make (high -ΔG = irreversible pathway)
- Uracil has many groups that can undergo noncovalent interactions with enzymes; the free energy of binding can contribute to the catalytic activity of the enzyme
- Good leaving group (picks up / gives off glucose easily)
- Acts as a tag setting some hexoses with nucleotidyl groups aside for a particular purpose
