adenylylcyclas

Adenylyl cyclase, also known as adenylate cyclase, is a family of enzymes that catalyze the conversion of ATP to cyclic adenosine monophosphate (cAMP) and pyrophosphate. In organisms ranging from bacteria to humans, this reaction generates a pivotal second messenger that transmits signals from cell-surface receptors to intracellular targets, thereby regulating numerous physiological processes.

In mammals, adenylyl cyclases are divided into membrane-bound (nine isoforms, ADCY1–ADCY9) and soluble forms (ADCY10, also called soluble adenylyl cyclase or sAC). Membrane-bound ADCYs are typically activated by the Gs alpha subunit of heterotrimeric G proteins in response to G protein‑coupled receptor (GPCR) stimulation and inhibited by Gi/o. They require divalent metal ions, usually Mg2+ or Mn2+. The soluble form sAC is regulated by intracellular cues such as bicarbonate, calcium, and pH, and localizes to cytosolic and organelle compartments.

The primary product, cAMP, acts through multiple effectors to elicit cellular responses. Key targets include protein kinase A (PKA), exchange proteins directly activated by cAMP (Epac), and cyclic nucleotide-gated channels. Through these pathways, cAMP modulates metabolism, gene expression (via CREB), ion transport, muscle tone, neuronal signaling, and memory formation.

Regulation and localization of ADCY isoforms are tissue-specific, contributing to diverse physiological roles. Forskolin is a pharmacological activator that directly stimulates adenylyl cyclase activity, while mutations or dysregulation of ADCY genes have been associated with cardiovascular, metabolic, and neuropsychiatric disorders. In bacteria, adenylyl cyclases produce cAMP to regulate carbon metabolism via the cAMP-CRP system, illustrating the broad evolutionary role of this enzyme family.