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Adenylyl cyclase

Synonyms: adenyl cyclase, adenylate cyclase, AC
German: Adenylatzyklase, Adenylylzyklase

1 Definition

Adenylyl cyclase is a membrane-bound enzyme which produces cAMP from ATP after an appropriate stimulus. This makes adenylyl cyclase an important component of second messenger signal transduction pathways. Guanylate cyclases produce cGMP from GTP.

2 Structure

As an important enzyme of the cell membrane, adenylyl cyclase is a G protein-regulated protein that is located on the inner membrane surface. It comprises twelve transmembrane domains with a lengthy loop between the sixth and seventh domain. This is the place where the interaction with G proteins is thought to take place.

Several isozymes of adenylyl cyclase have been described. Adenylyl cyclase type I occurs in neuronal tissue, whereas types IV, V, and VI can be found in the liver, lungs, heart, and kidney.

3 Function

Adenylyl cyclase belongs to the group of lyases because it catalyzes the separation of chemical bonds. One round of catalysis results in bond breaking of one substrate unit.

The reaction results in the formation of cyclic adenosine monophosphate (cAMP) from 5'-adenosine triphosphate (ATP). In addition to cAMP, the reaction yields pyrophosphate which is immediately broken down into two inorganic phosphates and thus makes the reaction irreversible.

3.1 Second messenger

As a product of the adenylyl cyclase reaction, cAMP plays an important role in the second messenger pathways of metabolism and signal transduction. It activates protein kinase A which in turn phosphorylates further enzymes and thus influences metabolic pathways. Whether this phosphorylation causes an activation or inactivation of an enzyme depends on the enzyme itself and its particular function.

3.2 Gene expression

Furthermore, cAMP regulates the gene expression of some enzymes and hormones, e.g. somatostatin, PEP carboxykinase, parathyroid hormone, or vasoactive intestinal peptide (VIP).

3.3 Variability

The adenylyl cyclase protein can be activated or inhibited by the alpha-subunit of a stimulating or inhibitory G protein, respectively. Which G protein comes into effect depends on the particular receptor which binds the messenger substance.

The group of G protein-gated adenylyl cyclase associated hormones or messenger substances includes ACTH, dopamine, glucagon, adrenaline and noradrenaline, histamine, oxytocin and others. Their effects in various cells are diverse and depend on the particular receptor.

4 Pathophysiology

Cholera toxin blocks the GTPase enzyme which results in the constant stimulation of adenylyl cyclase which brings about permanently increased cAMP levels due to the missing deactivation of the hormonally activated G protein.

The pertussis toxin also leads to permanently increased cAMP levels with the according effects. In this case, however, the inhibitory G protein is inhibited as well which causes the disinhibition of adenylyl cyclase.

This page was last edited on 30 August 2017, at 21:23.

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