Adenylate cyclase (AC) is an enzyme that is involved in regulating a cell’s response to many hormones. It synthesizes an important cellular regulator that helps amplify signals from outside of the cell. This enzyme is also known as adenylyl cyclase or adenyl cyclase.
Some hormones cannot enter cells, and to take affect, they bind to receptors on a cell’s membranes. The hormone-receptor complex transmits a signal to a component inside the cell. For example, when adrenaline binds at the cell membrane, its receptor complex binds to a G protein. This induces a change in the structure of the G protein, which then binds to inactive adenylate cyclase. If the G protein is a stimulating type, this binding activates the adenylate cyclase to catalyze the synthesis of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP).
cAMP is a widespread compound in cellular metabolism, for instance stimulating the breakdown of a stored glucose polymer to form glucose molecules that circulate in the blood. It is known as an intracellular secondary messenger, because it transmits signals from outside of the cell to the intracellular machinery. The activity of many enzymes is regulated by the addition of a phosphate group, and one of the activities of cAMP is to activate a group of enzymes known as protein kinase A, which add phosphate groups to other enzymes. The addition of a phosphate group is known as phosphorylation and can activate or repress the activity of an enzyme.
Each molecule of cAMP can activate approximately 100 molecules of protein kinase A. Then that activated enzyme can phosphorylate about the same number of additional enzymes, which then phosphorylate other enzymes. Thus, as the signal is transmitted, its strength grows greatly. One molecule of adrenaline acting through adenylate cyclase can result in the activation of hundreds of thousands of enzymes within the cell. This increase is referred to as amplification.
There are ten different types of adenylate cyclase identified so far in mammals. They vary greatly in their mode of regulation and the type of tissue they are expressed in. This shows the great complexity of the adenylate cyclase activating system. Some of the enzymes require calcium, in addition to G proteins, to stimulate their activity. Other G proteins are inhibitory.
A large number of hormones act to either increase or decrease cAMP concentrations. Additional hormones that act through adenylate cyclase include glucagon, gastrin, secretin, pituitary hormones, and calcitonin. It is important for the metabolism of the cell that cAMP levels be tightly regulated.
Many pathogenic bacteria disrupt the concentrations of cAMP by secreting toxins. For instance, cholera toxin stimulates adenylate cyclase. Its prolonged activity leads to extreme dehydration, which can be fatal.