Adenylyl cyclase !

The enzyme that turns ATP into cAMP when a hormone activates a Gs-coupled receptor; it is the signal's amplifier.

Updated 2026-11-01

Loading the 3D model…

Key facts

Reaction: ATP → cAMP + pyrophosphate, with two Mg²⁺ ions in the active site.
Gαs activates it and Gαi inhibits it; so glucagon and adrenaline (β) raise cAMP, and adrenaline (α2) or somatostatin lower it.
Nine membrane isoforms (ADCY1–9) with 12 transmembrane helices and two inner catalytic domains (C1 and C2); ADCY10 is soluble and responds to bicarbonate.
Structure 4CLK is human soluble cyclase with a non-hydrolysable ATP analogue in the active site, the same C1/C2 catalytic fold as the membrane forms.

Stimulation by Gαs (glucagon, β-adrenergic, ACTH, TSH, PTH, ADH V2 receptors).
Inhibition by Gαi (α2, M2, D2, opioid, somatostatin receptors).
Ca²⁺/calmodulin activates some isoforms (AC1, AC8) and inhibits others (AC5, AC6).
Forskolin directly activates the membrane isoforms.

P-site adenosine analogues (experimental use)
Pertussis toxin (indirect: stops Gαi from braking it, so it leaves it more active)

Cholera toxin keeps Gαs on: the enterocyte cyclase makes cAMP non-stop and causes secretory diarrhoea.
Activating GNAS (gsp) mutations in the pituitary raise cAMP and cause GH-secreting adenomas.
ADCY5 mutations cause a movement disorder starting in childhood (dyskinesia).

Think of the answer, then tap the question to see it.

Which reaction does adenylyl cyclase catalyse?

It turns ATP into cyclic AMP and pyrophosphate.

Which G protein subunit inhibits adenylyl cyclase?

Gαi, activated by receptors such as the α2-adrenergic or somatostatin receptor.

Why does cholera toxin raise enterocyte cAMP?

Because it keeps Gαs permanently on, and Gαs keeps adenylyl cyclase switched on.

Educational information, not medical advice. For any symptom, see a health professional.

Sources: ADCY5: Adenylate cyclase type 5 (human) (UniProt, 2026); ADCY10: Adenylate cyclase type 10 (human) (UniProt, 2026); 4CLK: Crystal structure of human soluble Adenylyl Cyclase in complex with alpha,beta-methyleneadenosine-5'-triphosphate (RCSB Protein Data Bank, 2026); GNAS gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.