Cyclic adenosine monophosphate

Cyclic adenosine monophosphate (cAMP, cyclic AMP or 3'-5'-cyclic adenosine monophosphate) is a molecule that is important in many biological processes; it is derived from adenosine triphosphate (ATP).

Functions
cAMP is a second messenger, used for intracellular signal transduction, such as transferring the effects of hormones like glucagon and adrenaline, which cannot get through the cell membrane. Its main purpose is the activation of protein kinases; it is also used to regulate the passage of Ca2+ through ion channels.

cAMP synthesis and decomposition
cAMP is synthesised from ATP by adenylate cyclase which is located at the cell membranes. Adenylate cyclase is activated by the hormones glucagon and adrenaline and inhibited by adenosine (via G protein coupled receptors). Liver adenylate cyclase responds more strongly to glucagon, and muscle adenylate cyclase responds more strongly to adrenaline.

cAMP decomposition into AMP is catalyzed by the enzyme phosphodiesterase.

Protein kinase activation
Cyclic AMP is involved in some protein kinases. For example, PKA (protein kinase A, also known as cAMP-dependent protein kinase) is normally inactive as a tetrameric holoenzyme, consisting of 2 catalytic and 2 regulatory units (C2R2), with the regulatory units blocking the catalytic centers of the catalytic units.

Cyclic AMP binds to specific locations on the regulatory units of the protein kinase, and causes dissociation between the regulatory and catalytic subunits, thus activating the catalytic units and enabling them to phosphorylate substrate proteins.

Glycogen decomposition regulation
cAMP controls many biological processes, including glycogen decomposition into glucose (glycogenolysis), and lipolysis.

Role of cAMP in bacteria
In bacteria, the level of cAMP varies depending on the medium used for growth. In particular, cAMP is low when glucose is the carbon source. This occurs through inhibition of the cAMP-producing enzyme, adenylate cyclase, as a side effect of glucose transport into the cell. The transcription factor CRP, cAMP receptor protein (or CAP) forms a complex with cAMP and thereby is activated to bind to DNA. CRP-cAMP increases expression of a large number of genes, including some encoding enzymes that can supply energy independent of glucose.

An example of cAMP's function is the positive regulation of the lac operon. In an environment of a low glucose concentration, cAMP accumluates and binds to the allosteric site on CRP, a transcription activator protein. The protein assumes its active shape and binds to a specific site beside the lac promoter, making it easier for RNA polymerase to bind to the adjacent promoter to start transcription of the lac operon, increasing the rate of lac operon transcription. With a high glucose concentration, the cAMP concentration decreases, and the CRP disengages from the lac operon.

Role of cAMP in Dictyostelium discoideum
The chemotactic movements of the cells are organized by periodic waves of cAMP that propagate through the cell. The waves are the result of a regulated production and secretion of extracellular cAMP and a spontaneous biological oscillator that initiates the waves at centers of territories.

Role of cAMP in human carcinoma
Some research has suggested that a deregulation of cAMP pathways and an aberrant activation of cAMP-controlled genes is linked to the growth of some cancers.