Signal Transduction: cAMP and PKA Pathway
Signal transduction is one of the highest-yield advanced biochemistry topics for the MCAT B/B section. The cAMP-PKA pathway begins when a ligand (e.g., epinephrine, glucagon) binds a G-protein coupled receptor (GPCR) on the cell surface. The receptor undergoes a conformational change that activates the associated G-protein by exchanging GDP for GTP on the Gα subunit. The activated Gαs subunit dissociates from Gβγ and activates adenylyl cyclase (AC), which converts ATP to cyclic AMP (cAMP). cAMP is the second messenger — it activates protein kinase A (PKA) by binding the regulatory subunits, releasing the active catalytic subunits. PKA then phosphorylates target proteins, activating or inhibiting them depending on context. In liver cells: PKA phosphorylates glycogen phosphorylase kinase (activating it), which activates glycogen phosphorylase (glycogen breakdown) — simultaneously, PKA phosphorylates and inactivates glycogen synthase. Result: epinephrine/glucagon signal → glycogen breakdown, glucose release. Signal termination: phosphodiesterase (PDE) hydrolyzes cAMP to AMP, ending the signal. Gi (inhibitory G-protein) pathways inhibit adenylyl cyclase, reducing cAMP. The Gαi pathway is activated by receptors such as α2-adrenergic receptors and opioid receptors — clinically relevant for understanding drug mechanisms.