Lecture 10 - Glycogenolysis

Question 1

Describe Glycogenolysis

Answer 1

1. Glycogen degradation
   The 1,4 glycosidic bond between the end and penultimate glucose on the end of a branch of glycogen is broken and a phosphate is then added to Carbon 1 of the removed glucose forming Glucose 1-phosphate. The reaction is catalysed by Glycogen phosphorylase
   The phosphorylase cleaves to within four residues of the branch point. When the last four residues are reached the three end residues are transferred to the end of another branch by oligo(α1,4–>α1,4)glucanotransferase. The single remaining glucose is then removed by α(1-6)glucosidase. The extended branch can then be attacked once more.
2. Glucose-1-phophate is converted to Glucose-6-phosphate which is catalysed by phosphoglucomutase.
3. The Glucose-6-phosphate is then in tissues other than thee liver used in glycolysis as it is trapped in the tissue, but in the case of the liver and kidney is dephosphorylated to form glucose which can then be transported in the blood this reaction is catalysed by glucose-6-phosphatase. It is able to leave the liver and kidney as it is dephosphorylated so can travel through transporters.

Question 2

Name four methods of enzyme regulation

Answer 2

1. Enzyme Kinetics
   
   2. Enzyme distribution
   3. Allosteric control
   4. Reversible phosphorylation

Question 3

Describe how glucose-6-phosphate regulates glycogenesis.

Answer 3

Glycogenesis (synthesis) and glycogenolysis (breakdown) are allosterically controlled by glucose-6-phophate:

Glucose-6-phosphate inhibits the enzyme activity of glycogen phosphorylase, which catalyzes the breakdown of glycogen to glucose-1-phosphate (ultimately leading to glucose release).

Glucose-6-phosphate activates the enzyme activity of glycogen synthase, which catalyzes the synthesis of glycogen from UDP-glucose (resulting in less glucose in the blood and more stored as glycogen).

Question 4

How is glycogenolysis regulated by hormonal control?

Answer 4

Insulin and glucagon are peptide hormones secreted by the pancreas. The pancreas contains clusters of cells called islets of Langerhans
* Glucagon is secreted by α-cells
* Insulin is secreted by β-cells - stimulates glycogen synthesis and glycolysis
There is a swift and sensitive response by these hormones to changes in blood glucose.

Hormonal control in Glycogenesis
(a = active form) (b = inactive form)

Activation
Insulin activates a protein phosphatase which removes the extra phosphates from glycogen synthase activating is leading to the production of glucagon.

Inhibition
Glucagon and adrenaline act on receptors causing cAMP to activate protein kinase which phosphorylates glycogen synthase a deactivating it so glucagon is not made.

Question 5

What is glycolysis?

Answer 5

Glucose —> energy (anaerobic)
Glycolysis is a metabolic process carried out by all cells to provide energy. Glucose is converted to two molecules of pyruvate and two molecules of ATP are synthesised.
There are two stages
1. Preparatory/investment phase
2. Payoff phase
The pyruvate formed in this process can then enter the citric acid cycle if oxygen and mitochondria are available

Question 6

Describe phase I of glycolysis

Answer 6

1. Glycose using ATP is converted to Glucose-6-phosphate. The reaction is catalysed by hexokinase in most tissues or glucokinase in the liver.
   
   2. The groups are re-arranged and fructose-6-phosphate is produced. The reaction is catalysed by glucose-6-phophate isomerase
   3. Using ATP a second phosphate is added to C1 of the fructose-6-phosphate forming Fructose-1,6-biphophate
   4. The Fructose-1,6-biphosphate is split into two 3C molecules. Glyceraldehyde-3-phosphate (G3P) and Dihydroxyacetone phosphate (DHAP). The reaction is catalysed by fructose-1,6-biphophate aldolase
   5. The DHAP is converted into G3P by triosephosphate isomerase