Glucagon signal transduction pathway Flashcards
Describe glucagon
It is a peptide hormone with 29 Amino acids. Synthesised in alpha cells of the pancreas (where the blood glucose levels are monitored).
Describe the glucagon receptor
It is a GPCR receptor, 7 membrane-spanning alpha-helices. Change in conformation upon binding the glucagon propagates the signal.
Describe the Guanyl Nucleotide (G)protein
G protein within membrane coupled with GPCR. alpha subunit breaks off and binds GTP, becoming active as the protein dissociates
Describe cAMP
This is made from ATP by the membrane bund enzyme Adenylate cyclase (AC)
Adenosine triphosphate -> AC -> cAMP
Describe protein kinase A
Protein kinase A has two regulatory subunits and 2 catalytic subunits. These subunits are bound together. When cAMP binds the regulatory subunits, they change conformation and dissociate from the catalytic subunits, which activates the protein kinase A allosterically.
What are the five main targets for the Protein Kinase A once it has been activated?
1) Bifunctional PFK-2/FBPase-2 enzyme
2) L-Pyruvate kinase
3) Glycogen synthase
4) Glycogen phosphorylase
5) Phosphoenolpyruvate carboxykinase (PEPCK)
How does the glucagon signal pathway affect the Bifunctional PFK-2/FBPase-2 enzyme
PFK-2 catalyses F-6-P to F-2,6-Bp and FBPase-2 catalyses the reverse reaction. When Protein kinase A phosphorylates the Ser residue on the N terminal, this turns off the kinase (PFK-2) domain but activates the bisphosphatase (FBPase-2) domain.
This effects glycolysis as it prevents the forwards PFK-1 pathway and activates the FBPase-1 pathway (Inhibits glycolysis, activates gluconeogenesis pathway)
How does the glucagon signal pathway affect L-Pyruvate kinase
cAMP inactivates liver-pyruvate kinase, preventing the final step in glycolysis. This means any pyruvate in the mitochondria will go though the gluconeogenesis pathway, and return back to glucose. (Pyruvate will be converted to oxaloacetate ad then PEP)
How does the glucagon signal pathway affect Glycogen synthase
Protein Kinase A phosphorylates glycogen synthase which inhibits the production of glycogen
How does the glucagon signal pathway affect Glycogen phosphorylase
Protein kinase A will phosphorylate phosphorylase kinase, activating it, which in turn phosphorylates glycogen phosphorylase = activating it. This promotes the breakdown of glycogen into glucose.
How does the glucagon signal pathway affect Phosphoenolpyruvate carboxykinase (PEPCK)
Protein kinase A phosphorylates CREB protein (Transcriptional regulator). This will bind DNA and promotion of the formation of a gene. This promotes the formation of mRNA, which is translated into PEPCK.
PEPCK catalyses pyruvate back to PEP via oxaloacetate.
