describe the principles of cell signalling using the example of the control of blood glucose concentration by glucagon, limited to: binding of hormone to cell surface receptor causing conformational change, activation of G-protein leading to stimulat
Homeostasis in Mammals – Cell Signalling (Glucagon)
Homeostasis in Mammals – Control of Blood Glucose by Glucagon
Overview
Glucagon is a peptide hormone released from the α‑cells of the pancreas when blood glucose falls. It restores glucose levels by activating a signalling cascade that ultimately stimulates the breakdown of glycogen in liver cells.
Key Steps in the Signalling Pathway
Hormone binding: Glucagon binds to a specific G‑protein‑coupled receptor (GPCR) on the hepatocyte plasma membrane, causing a conformational change in the receptor.
G‑protein activation: The altered receptor promotes exchange of GDP for GTP on the α‑subunit of the heterotrimeric G‑protein, releasing the α‑subunit from the βγ‑complex.
Stimulation of adenylyl cyclase: The GTP‑bound α‑subunit interacts with and activates adenylyl cyclase, an integral membrane enzyme.
Second messenger formation: Activated adenylyl cyclase catalyses the conversion of ATP to cyclic adenosine monophosphate (\$cAMP\$). \$cAMP\$ diffuses through the cytosol.
Activation of protein kinase A (PKA):\$cAMP\$ binds to the regulatory subunits of PKA, causing release of the catalytic subunits.
Enzyme cascade (amplification): The catalytic subunits of PKA phosphorylate multiple downstream targets, including:
Phosphorylase kinase (activates it)
Other metabolic enzymes that modulate glycogen synthesis
Final cellular response: Phosphorylated phosphorylase kinase activates glycogen phosphorylase a, the enzyme that catalyses the phosphorolytic cleavage of glycogen to \$Glucose\text{-}1\text{-}phosphate\$, which is rapidly converted to \$Glucose\text{-}6\text{-}phosphate\$ and released into the bloodstream.
Signal Amplification
Each activated PKA catalytic subunit can phosphorylate many molecules of phosphorylase kinase, and each phosphorylated phosphorylase kinase can activate multiple glycogen phosphorylase molecules. This hierarchical phosphorylation results in a large cellular response from a single hormone‑receptor interaction.