Transmembrane Receptors: Naturally coupled to G-protein.
G-protein Composition:
Three subunits: Alpha, Beta, Gamma.
Alpha Subunit:
Inactive state: Bound to GDP molecule.
Activation Process
Ligand Binding:
Can be an internal molecule or a drug.
Binds to the extracellular domain of receptors.
Activates the receptor.
GTP Replacement:
GDP on the alpha subunit is replaced by GTP.
Alpha-GTP subunit dissociates from beta and gamma subunits.
Mechanism of Action
Adenylal Cyclase Activation:
Alpha-GTP binds to membrane-attached adenylal cyclase enzyme.
Activates adenylal cyclase.
Conversion of ATP to cyclic AMP:
Catalyzed by active adenylal cyclase enzyme.
Role of Cyclic AMP
Activation of pKa:
Cyclic AMP converts inactive protein kinase A (pKa) to active form.
Cellular Effects:
Active pKa phosphorylates and activates numerous cellular enzymes.
Induces cascades of biological effects.
A single ligand can trigger multiple cellular reactions through this amplification process.
Summary
Significance: A single ligand activation can lead to a large-scale cellular response due to the cascade of reactions initiated by the active form of pKa.