Adenylate cyclase 6 (ADCY6) (ADCY6)

Adenylate cyclase 6 (ADCY6) is a membrane-bound enzyme that plays a pivotal role in the signal transduction pathways of colonic epithelial cells by catalyzing the conversion of ATP into cyclic AMP (cAMP) [1]. In the intestinal mucosa, ADCY6 activity is tightly regulated by G protein-coupled receptors (GPCRs), where stimulatory G proteins (Gs) increase cAMP production and inhibitory G proteins (Gi) decrease it [2]. The generated cAMP serves as a secondary messenger that activates protein kinase A (PKA), leading to the phosphorylation and activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel [3]. This activation results in the secretion of chloride ions and water into the intestinal lumen, a process essential for normal bowel function but one that can be pathologically hijacked [2]. For instance, the cholera toxin causes permanent activation of the Gs protein, which in turn leads to constitutive activation of adenylate cyclase and the massive fluid loss characteristic of secretory diarrhea [3]. Therapeutically, this pathway is targeted indirectly by somatostatin analogs like octreotide, which bind to Gi-coupled receptors to inhibit adenylate cyclase activity and reduce excessive intestinal secretion [4].

Other names

Adenylyl cyclase 6ATP pyrophosphate-lyase 6Adenylate cyclase type VIAdenylate cyclase type 6

Catalyzes the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) and pyrophosphate, which then activates downstream effectors like protein kinase A (PKA) and the CFTR channel.