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[Biochemistry](https://durgical.com/en/biochemistry/) · Enzyme

# 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

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## 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.

**Also called**
Adenylate cyclase, AC

**EC number**
[4.6.1.1](https://www.enzyme-database.org/query.php?ec=4.6.1.1)

**Genes**
ADCY1–ADCY9, ADCY10

**Structure (PDB)**
[4CLK](https://www.rcsb.org/structure/4CLK)

## Regulation

- 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.

## Inhibitors and toxins

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

## Clinical notes

- 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).

## Related conditions

- [Pituitary adenoma](https://durgical.com/en/conditions/pituitary-adenoma/)

## Related

- [Cyclic AMP (cAMP)](https://durgical.com/en/biochemistry/molecules/cyclic-amp/)
- [Protein kinase A (PKA)](https://durgical.com/en/biochemistry/enzymes/protein-kinase-a/)
- [G protein-coupled receptors and cAMP](https://durgical.com/en/biochemistry/topics/g-protein-coupled-receptors-and-camp/)
- [Glucagon signalling](https://durgical.com/en/biochemistry/topics/glucagon-signalling/)
- [Adrenaline](https://durgical.com/en/biochemistry/molecules/adrenaline/)
- [ATP (adenosine triphosphate)](https://durgical.com/en/biochemistry/molecules/atp/)

## Test yourself

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.

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

Sources: [ADCY5: Adenylate cyclase type 5 (human)](https://www.uniprot.org/uniprotkb/O95622/entry) (UniProt, 2026); [ADCY10: Adenylate cyclase type 10 (human)](https://www.uniprot.org/uniprotkb/Q96PN6/entry) (UniProt, 2026); [4CLK: Crystal structure of human soluble Adenylyl Cyclase in complex with alpha,beta-methyleneadenosine-5'-triphosphate](https://www.rcsb.org/structure/4CLK) (RCSB Protein Data Bank, 2026); [GNAS gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/gnas/) (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).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/adenylyl-cyclase/