Which of the following enzymes is directly activated by cAMP through allosteric binding to its regulatory subunit?

Explanation

## cAMP-Dependent Signaling Mechanism **Key Point:** cAMP exerts its effects primarily through activation of protein kinase A (PKA), a cAMP-dependent protein kinase. ### Mechanism of PKA Activation 1. **Inactive state**: PKA exists as an inactive holoenzyme complex consisting of two regulatory (R) subunits and two catalytic (C) subunits (R₂C₂). 2. **cAMP binding**: When cAMP levels rise, four molecules of cAMP bind cooperatively to the two R subunits (two per R subunit). 3. **Dissociation**: cAMP binding causes conformational change and dissociation of the catalytic subunits from the regulatory subunits. 4. **Activation**: Free catalytic subunits are now enzymatically active and phosphorylate target proteins on serine and threonine residues. **High-Yield:** The allosteric binding of cAMP to the regulatory subunit is the critical step that converts inactive PKA into its active form. This is the primary mechanism by which cAMP exerts its intracellular effects. ### cAMP Signaling Cascade ```mermaid flowchart LR A[Hormone binds GPCR]:::outcome --> B[Gs protein activated]:::action B --> C[Adenylyl cyclase activated]:::action C --> D[ATP → cAMP]:::action D --> E[cAMP binds R subunit of PKA]:::action E --> F[C subunits dissociate & activate]:::action F --> G[Phosphorylation of target proteins]:::outcome ``` **Clinical Pearl:** Different tissues express different PKA isoforms (PKA-I and PKA-II) with different localizations, allowing tissue-specific responses to cAMP despite the same second messenger. **Mnemonic:** **CAMP** = **C**AMP **A**ctivates **M**ultiple **P**roteins (via PKA).