Editing Adenylyl cyclase (section)

==== Regulation ====
Adenylyl cyclase is regulated by G proteins, which can be found in the monomeric form or the heterotrimeric form, consisting of three subunits.<ref name=":0" /><ref name=":1" /><ref name=":2" /> Adenylyl cyclase activity is controlled by heterotrimeric G proteins.<ref name=":0" /><ref name=":1" /><ref name=":2" /> The inactive or inhibitory form exists when the complex consists of alpha, beta, and gamma subunits, with GDP bound to the alpha subunit.<ref name=":0" /><ref name=":2" /> In order to become active, a ligand must bind to the receptor and cause a conformational change.<ref name=":0" /> This conformational change causes the alpha subunit to dissociate from the complex and become bound to GTP.<ref name=":0" /> This G-alpha-GTP complex then binds to adenylyl cyclase and causes activation and the release of cAMP.<ref name=":0" /> Since a good signal requires the help of enzymes, which turn on and off signals quickly, there must also be a mechanism in which adenylyl cyclase deactivates and inhibits cAMP.<ref name=":0" /> The deactivation of the active G-alpha-GTP complex is accomplished rapidly by GTP hydrolysis due to the reaction being catalyzed by the intrinsic enzymatic activity of GTPase located in the alpha subunit.<ref name=":0" /> It is also regulated by [[forskolin]],<ref name=":3" /> as well as other isoform-specific effectors:

* Isoforms I, III, and VIII are also stimulated by [[calcium|Ca<sup>2+</sup>]]/[[calmodulin]].<ref name=":3" />
* Isoforms V and VI are inhibited by Ca<sup>2+</sup> in a calmodulin-independent manner.<ref name=":3" />
* Isoforms II, IV and IX are stimulated by alpha subunit of the G protein.<ref name=":3" />
* Isoforms I, V and VI are most clearly inhibited by Gi, while other isoforms show less dual regulation by the inhibitory G protein.<ref name=":3" />
* [[Soluble adenylyl cyclase|Soluble AC]] (sAC) is not a transmembrane form and is not regulated by G proteins or forskolin, instead acts as a bicarbonate/pH sensor. It is anchored at various locations within the cell and, with [[phosphodiesterases]], forms local cAMP signalling domains.<ref name="pmid24324443">{{cite journal | vauthors = Rahman N, Buck J, Levin LR | title = pH sensing via bicarbonate-regulated "soluble" adenylyl cyclase (sAC) | journal = Frontiers in Physiology | volume = 4 | pages = 343 | date = November 2013 | pmid = 24324443 | pmc = 3838963 | doi = 10.3389/fphys.2013.00343 | doi-access = free }}</ref>

In [[neuron]]s, calcium-sensitive adenylyl cyclases are located next to calcium [[ion channel]]s for faster reaction to Ca<sup>2+</sup> influx; they are suspected of playing an important role in learning processes. This is supported by the fact that adenylyl cyclases are ''coincidence detectors'', meaning that they are activated only by several different signals occurring together.<ref name=":4">{{cite journal | vauthors = Hogan DA, Muhlschlegel FA | title = Candida albicans developmental regulation: adenylyl cyclase as a coincidence detector of parallel signals | journal = Current Opinion in Microbiology | volume = 14 | issue = 6 | pages = 682–686 | date = December 2011 | pmid = 22014725 | doi = 10.1016/j.mib.2011.09.014 }}</ref>  In peripheral cells and tissues adenylyl cyclases appear to form molecular complexes with specific receptors and other signaling proteins in an isoform-specific manner.