Cyclic AMP functions as a second messenger to relay extracellular signals to intracellular effectors, particularly protein kinase A. Regulation of intracellular concentrations of cyclic AMP is largely a result in controlling adenylyl cyclase.
Adenylyl cyclases are integral membrane proteins that consist of two bundles of six transmembrane segments. Two catalytic domains extend as loops into the cytoplasm, as depicted in the figure to the right.
A soluble non-membrane bound form of adenylyl cyclase has recently been characterized in mammalian sperm. This form of the enzyme appears to be activated by bicarbonate ion.
There are at least nine isoforms of adenylyl cyclase, discovered by cloning of full-length cDNAs. Having said that, it certainly has never been the subject of a CICM exam question. As such, this entire subject area can be abandoned in favour of more fruitful revision topics; a Part One candidate may successfully negotiate the exam and then go on to have a rich fulfilling career in Intensive Care Medicine with only a very foggy and dream-like appreciation of cAMP and its functions.
Thus, most reasonable people would agree that the contents of this grey box will be enough:. If for whatever reason the candidate continues reading, it would be worth knowing that without resorting to piracy the best single article on this topic is The Cyclic AMP Pathway by Paolo Sassone-Corsi Another good resource is probably the original article by Sutherland et al , who ended up being awarded the Nobel Prize in Medicine for the discovery of this second messenger system it was the first second messenger system to be discovered.
The "cyclicness" is conveyed upon straight AMP by the bonds created between the phosphate group and the hydroxyl groups on the sugar, creating a little ring. This molecule is relatively short-lived. As a second messenger, it is a substance which by its very presence causes various chains of events to take place; as such its concentration is very precisely regulated.
Its synthesis by adenylyl cyclases and its catabolism by phosphodiesterases is in a constant equilibrium. When one tries to measure the rate of cAMP turnover, one usually finds its intracellular lifespan is measured in minutes or seconds. For instance, in cultured fibroblasts under conditions of low stimulus the half-life of cAMP is about 1.
It is an ester of phosphoric acid and the nucleoside adenosine. ATP forms a chain with other monomeric nucleotides.
However, cAMP does not form a chain. Adenosine monophosphate AMP is a nucleoside monophosphate in being comprised of a ribonucleoside and one phosphate group. It means it has a ribose as its sugar and one phosphate group attached. Its nucleoside contains a purine base, i. It has only one phosphate group attached to the nucleoside. It forms as a condensation product of adenosine and phosphoric acid. It is a nucleotide found among the hydrolysis products of all nucleic acids.
The process is catalyzed by adenylate cyclase that is located at the cell membrane. The enzyme is activated in turn by signaling molecules that bind to adenylate cyclase stimulatory G-protein-coupled receptors. It is used for intracellular signal transduction in many different organisms, conveying the cAMP-dependent pathway. In particular, it is used in transferring into cells the effects of glucagon and adrenaline.
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