Lecture 13. Glycogen Metabolism and Glucose Homeostasis Flashcards
What is glycogen?
A highly branched polymer of glucose residues
What is the main function of glycogen?
Serves as a store of glucose to maintain blood glucose by the liver and energy generation (muscle)
Why is glucose unsuitable for storage?
Glucose would require hydration
Where is glycogen stored?
As insoluble granules in the liver and skeletal muscle
Why does the body need to use glycogen for energy storage in addition to more abundant fat?
Fatty acids cannot be metabolised anaerobically
Blood glucose must be maintained to serve as fuel for the brain
Animals cannot convert fatty acids to glucose
What organisms can use the glyoxylate pathway?
Plants and bacteria
What process splits glycogen, what products are formed and what catalyses the reaction?
Phosphorolytic cleavage, glucose 1-phosphate + glycogen (n-1), glycogen phosphorylase
Glycogen breakdown process
- α-1,4 glycosidic bonds on each branch are cleaved till 4 residues left
- Transferase shifts a block of 3 residues from one branch to the other
- The branch point residue is removed by α-1,- glycosidase (debranching enzyme) leaving a linear chain
What is required for glycogen synthesis?
Input of energy - not a “reversal” of phosphorolytic cleavage
Glycogen synthesis
Glucose 1-phosphate couples with UTP cleavage to form uridine diphosphate glucose (UDPG)
UDPG reacts with glycogen to form UDP and a longer glycogen
What does the glycogen primer consist of?
Four or more α-1,4 linked glucose residues attached to a tyrosine in the protein
Contains glycogenin
A separate branching enzyme transfers blocks of ~ 7 glucose residues to interior sites and attaches the α-1,6 linkages
What do patients with Andersen’s disease lack?
The branching enzyme and so die early of liver failure
What enzyme converts UDP-glucose to glycogen?
Glycogensynthase
What enzyme converts glycogen to glucose-1-P?
Glycogenphosphorylase
Which hormones regulate the breakdown of glycogen?
Glucagon and adrenaline
What hormone regulates glycogen synthesis?
Insulin
Is phosphorylase activated or inactivated by phosphorylation?
Activated
Is glycogen synthase activated or inactivated by phosphorylation?
Inactivated
What happens when low blood glucose is detected?
Low insulin, glucagon release
Phosphorylase activation and glycogen synthase inactivation
Glycogen breakdown
Stress: Adrenalin release, same activation and inactivation as glucagon release
What happens when high blood glucose is detected?
High insulin, low adrenaline and glucagon
Glycogensynthase activation and phosphorylase inactivation
Glycogen synthesis
What does phosphorylase exist as?
A homodimer in relaxed (R) or tense (T) states
How does phosphorylation work in phosphorylase?
Equilibrium between the active relaxed (R) state and the inactive tense (T) state
Phosphorylase a is usually active because the equilibrium favours the R state
Phosphorylase b is usually inactive because the equilibrium favours the T state
What causes allosteric regulation in liver phosphorylase?
The binding of glucose to phosphorylase a shifts equilibrium to tense state, inactivating the enzyme
Definition of isoenzymes
Multiple forms of an enzyme that catalyse the same reaction but differ from each other in their primary structure, kinetic properties and allosteric regulation
Why does a marathon runner not rely so much on the Cori cycle?
Muscles are burning fuel aerobically
What is the Cori cycle?
The process of gluconeogenesis happening in the liver being linked with glycolysis in the muscle
