Lecture 4 Regulation of glucose homeostasis 2 Flashcards
Where are the 2 places that glucose homeostasis can be achieved by regulating glycogen metabolism?
Muscle and liver
What are the 2 levels that the regulation of glycogen metabolism can be achieved?
Allosteric regulation of glycogen synthase and glycogen phosphorylase.
Pathways of synthesis and breakdown are hormonally regulated.
What is glycogenolysis?
The breaking down of glycogen to yield glucose.
At which end of the glycogen molecule are the glucose residues removed?
The non-reducing end.
What enzyme removes glucose form glycogen?
Glycogen phosphorylase.
What for is glucose in when it is removed from glycogen by glycogen phosphorylase?
Glucose-1-phosphate.
After glucose-1-phosphate is removed from glycogen what happens to it?
It is converted into glucose-6-phosphate by phosphoglucomutase.
What fates can G-6-P have in the liver and muscle.
In muscle it can undergo glycolysis only, it cannot be dephosphorylated. In the liver it can also undergo glycolysis but can also be dephosphorylated into glucose to be transported out of the liver.
Where in the liver is G-6-P dephosphorylated?
In the endoplasmic reticulum.
What enzyme dephosphorylates G-6-P to glucose?
Glucose-6-phosphatase.
What are the steps in glycogen synthesis?
Glucose to G-6-P by hexokinase
G-6-P to G-1-P by phosphoglucomutase.
G-1-P to UDP-glucose by G-1-P uridylyltransferase.
UDP-glucose to UDP by glycogen synthase yielding the glucose to the glycogen molecule.
What is glycogenin?
It is a priming enzyme on which the glycogen molecule is synthesised.
How many glucose residues are in each glycogen chain?
12-14
How many tiers can a glycogen molecule have?
5
What is the initial signal for glycogen breakdown?
Glucagon or adranaline.
How does glucagon or adrenaline initiate glycogen breakdown?
It starts a signalling pathway, starting with a phosphorylation cascade via cAMP which activates glycogen phosphorylase.
Glycogen phosphorylase then cleaves glucose residues off glycogen generating G-1-P.
Adrenaline and glucagon stimulate glycogen breakdown in which tissues?
Adrenaline in the muscles.
Glucagon in the liver.
Why is phosphorylase a ‘glucose sensor’?
When glucose levels return to normal, glucose enters the liver cells and binds to an allosteric site on phosphorylase a to inhibit the enzyme. This inhibits glycogen breakdown.
How does insulin control glycogen synthesis?
Insulin signalling pathway increases glucose import into muscle, stimulates the activity of muscle hexokinase and activates glycogen synthase. The increased hexokinase activity enables activation of glucose. Glycogen synthase makes glycogen for energy storage.
How is glycogen synthase controlled by phosphorylation?
When glycogen synthase is phosphorylated it is in an inactivated form. In the presence of G-6-P, glucose or insulin it is dephosphorylated and therefore activated. This causes glycogen synthesis to begin.
