Question

. Explain the mechanism by which the signaling by the Epinephrine receptor is amplified inside the cell. And also explain the merit of signal amplification.

Answer 1

Adrenergic receptor ( AR) belongs to the family of G protein coupled receptors (GPCRs). Also known as 7TM or 7 Transmembrane receptors as they contain 7 transmembrne helices.

They utilize a trimeric, G protein for signalling. G is the inhibitory subunit which binds to the G subunit in the unstimulated state.

G has a bound GDP in the absence of ligand binding to receptor. Upon binding of ligand, a conformational change allows G to switch GDP for GTP. G/GTP can now get free of the inhibitory G subunit.

The active G/GTP binds to and activate adenylyl cyclase which converts ATP to cAMP.

cAMP acts as an allosteric activator for PKA which phodphoryltes the target proteins.

The ligand in this case is epinephrine.

1 molecule of epinephrine binds to 1 molecule of receptor. This can further activate 10 molecules of G each of which can activate adenylyl cyclase.which can produce 200 molecules of cAMP.

cAMP can further activate 100 PKA molecules each of which can phosphorylates 1000s of target molecules.

Signal amplification serves several purposes like fine tuning the action of an enzyme or signalling pathway. This makes the process sensitive to very small changes in concentration of ligands.