phosphodiesterase

Meaning: Phosphodiesterase (PDE) breaks the cyclic phosphodiester bond in cAMP and cGMP, producing AMP and GMP. Adenylyl cyclase makes cAMP from ATP, and PDE removes it, so the cAMP level reflects the balance between the two. PDE activity lets a cell turn off a signal after the hormone leaves its receptor.

Equation: cAMP + H₂O → AMP, where cAMP is cyclic adenosine monophosphate, AMP is adenosine monophosphate, and H₂O is water. Amounts are in mol (concentrations in mol/m³, often written mol/L). cGMP is converted to GMP in the same way.

On the MCAT: A passage gives a GPCR pathway (hormone → Gs → adenylyl cyclase → cAMP → protein kinase A) and asks what happens when PDE is inhibited. Caffeine is a PDE inhibitor, so cAMP stays elevated, protein kinase A stays active longer, and the response is prolonged or enhanced. A second use is phototransduction: light-activated rhodopsin activates transducin, which activates PDE. PDE lowers cGMP, cGMP-gated Na⁺ channels close, and the rod hyperpolarizes.

Common confusion: PDE is not adenylyl cyclase. Cyclase builds cAMP and PDE destroys it, so their effects on cAMP are opposite. PDE is also not a protein phosphatase, which removes phosphate groups from proteins. In rods, more PDE activity means less cGMP, which is the reverse of the usual "signal up" pattern.