adenylcyclase

Adenylyl cyclase, also known as adenylate cyclase, is an enzyme that catalyzes the conversion of ATP to cyclic adenosine monophosphate (cAMP) and pyrophosphate. cAMP serves as a ubiquitous second messenger in cellular signaling, linking extracellular stimuli to intracellular responses.

There are two major classes of adenylyl cyclases in eukaryotes. Membrane-bound adenylyl cyclases (tmACs) are embedded in the plasma membrane and are encoded by multiple ADCY genes (for example, ADCY1 through ADCY9 in humans). These enzymes are typically regulated by G proteins: stimulation by Gs increases activity, while Gi inhibits it. They can be directly activated by forskolin, and several isoforms are modulated by calcium/calmodulin and other intracellular factors. Soluble adenylyl cyclase (sAC, encoded by ADCY10) exists in the cytosol and within organelles; it is regulated by bicarbonate and calcium, and it is not controlled by heterotrimeric G proteins. The two classes contribute to distinct spatial and temporal pools of cAMP within the cell.

Functionally, cAMP produced by adenylyl cyclase activates effector proteins such as protein kinase A (PKA) and exchange proteins directly activated by cAMP (EPAC), among others, thereby influencing metabolism, gene expression, neuronal signaling, muscle function, and more. Signal termination is achieved primarily through phosphodiesterases that hydrolyze cAMP to AMP, enabling precise control over signaling duration and localization.

Adenylyl cyclase activity is conserved across organisms, with bacteria also possessing cAMP-producing enzymes that regulate transcriptional responses via cAMP-responsive elements. In eukaryotes, the versatility and regulation of the ADCY family underpin a wide range of physiological processes.