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Cyclic Adenosine Monophosphate

 
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Cyclic adenosine monophosphate (cAMP, cyclic AMP or 3'-5'-cyclic adenosine monophosphate
Adenosine monophosphate

Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is found in RNA. It is an ester of phosphoric acid and the nucleoside adenosine....
) is a second messenger that is important in many biological processes. cAMP is derived from adenosine triphosphate
Adenosine triphosphate

This article is about the chemical used by cells as an energy carrier. For other uses, see ATP .Adenosine-5'-triphosphate is a multifunctional nucleotide, and plays an important role in cell biology as a coenzyme that is the "molecule unit of currency" of intracellular energy transfer....
 (ATP) and used for intracellular signal transduction
Signal transduction

In biology, 'signal transduction' refers to any process by which a cell converts one kind of signal or stimulus into another. Most processes of signal transduction involve ordered sequences of biochemistry chemical reaction inside the cell, which are carried out by enzymes, activated by Second messenger systems, resulting in a signal tran...
 in many different organisms.

is synthesised from ATP by adenylyl cyclase which is located at the cell membranes. Adenylyl cyclase is activated by a range of signaling molecules through the activation of adenylyl cyclase stimulatory G (Gs
Gs alpha subunit

The Gs alpha subunit is a heterotrimeric G protein subunit which activates adenylate cyclase. Researchers have discovered that a change in the location of this protein in the brain could serve as a biomarker for depression, allowing a simple, rapid, laboratory test to identify patients with depression....
)-coupled receptors and inhibited by agonists of adenylyl cyclase inhibitory G (Gi)-protein coupled receptors.






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Cyclic adenosine monophosphate (cAMP, cyclic AMP or 3'-5'-cyclic adenosine monophosphate
Adenosine monophosphate

Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is found in RNA. It is an ester of phosphoric acid and the nucleoside adenosine....
) is a second messenger that is important in many biological processes. cAMP is derived from adenosine triphosphate
Adenosine triphosphate

This article is about the chemical used by cells as an energy carrier. For other uses, see ATP .Adenosine-5'-triphosphate is a multifunctional nucleotide, and plays an important role in cell biology as a coenzyme that is the "molecule unit of currency" of intracellular energy transfer....
 (ATP) and used for intracellular signal transduction
Signal transduction

In biology, 'signal transduction' refers to any process by which a cell converts one kind of signal or stimulus into another. Most processes of signal transduction involve ordered sequences of biochemistry chemical reaction inside the cell, which are carried out by enzymes, activated by Second messenger systems, resulting in a signal tran...
 in many different organisms.

Synthesis and decomposition

cAMP is synthesised from ATP by adenylyl cyclase which is located at the cell membranes. Adenylyl cyclase is activated by a range of signaling molecules through the activation of adenylyl cyclase stimulatory G (Gs
Gs alpha subunit

The Gs alpha subunit is a heterotrimeric G protein subunit which activates adenylate cyclase. Researchers have discovered that a change in the location of this protein in the brain could serve as a biomarker for depression, allowing a simple, rapid, laboratory test to identify patients with depression....
)-coupled receptors and inhibited by agonists of adenylyl cyclase inhibitory G (Gi)-protein coupled receptors. Liver adenylyl cyclase responds more strongly to glucagon, and muscle adenylyl cyclase responds more strongly to adrenaline.

cAMP decomposition into AMP is catalyzed by the enzyme phosphodiesterase
Phosphodiesterase

A phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below....
.

Functions

cAMP is a second messenger, used for intracellular signal transduction, such as transferring the effects of hormone
Hormone

Hormones are chemicals released by cells that affect cells in other parts of the body. Only a small amount of hormone is required to alter cell metabolism....
s like glucagon
Glucagon

Glucagon is an important hormone involved in carbohydrate metabolism. Produced by the pancreas, it is released when the glucose level in the blood is low , causing the liver to convert stored glycogen into glucose and release it into the bloodstream....
 and adrenaline, which cannot get through the cell membrane. Its purposes include the activation of protein kinase
Protein kinase

A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme catalysis, cellular location, or association with other proteins....
s and regulating the effects of adrenaline and glucagon. It is also used to regulate the passage of Ca2+
Calcium

Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft grey alkaline earth metal, and is the fifth most abundant element by mass in the earth's Crust ....
 through ion channels.

In humans

G Protein Signal Transduction (epinephrin Pathway)
cAMP and its associated kinases function in several biochemical processes, including the regulation of glycogen
Glycogen

Glycogen is a polysaccharide of glucose which functions as the secondary short term energy storage in animal cells. It is made primarily by the liver and the muscles, but can also be made by the brain and stomach....
, sugar
Sugar

Sugar is a class of edible crystalline substances, mainly sucrose, lactose, and fructose. Human taste buds interpret its flavor as sweet. Sugar as a basic food carbohydrate primarily comes from sugar cane and from sugar beet, but also appears in fruit, honey, sorghum, sugar maple , and in many other sources....
, and lipid
Lipid

Lipids are broadly defined as any fat-soluble , naturally-occurring molecule, such as fats, oils, waxes, cholesterol, sterols, fat-soluble vitamins , monoglycerides, diglycerides, phospholipids, and others....
 metabolism
Metabolism

Metabolism is the set of chemical reactions that occur in living organisms in order to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments....
.

In humans, cyclic AMP works by activating protein kinase A (PKA, also known as cAMP-dependent protein kinase
CAMP-dependent protein kinase

In cell biology, protein kinase A refers to a family of enzymes whose activity is dependent on the level of cyclic AMP in the cell. PKA is also known as cAMP-dependent protein kinase )....
). This is normally inactive as a tetrameric holoenzyme, consisting of 2 catalytic
Catalysis

Catalysis is the process in which the reaction rate of a chemical reaction is either increased or decreased by means of a chemical substance known as a catalyst....
 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.

The active subunits catalyze the transfer of phosphate from ATP to specific serine or threonine residues of protein substrates. The phosphorylated proteins may act directly on the cell's ion channels, or may become activated or inhibited enzymes. Protein kinase A can also phosphorylate specific proteins that bind to promoter regions of DNA, causing increased expression of specific genes. Not all protein kinases respond to cAMP: several types of protein kinases are not cAMP dependent, for example protein kinase C.

Further effects depend on cAMP-dependent protein kinase, which vary based on the type of cell.

In non-humans


Role of cAMP in bacteria
Bacteria

The Bacteria are a large group of unicellular microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals....
 
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, adenylyl cyclase, as a side effect of glucose transport into the cell. The transcription factor cAMP receptor protein
CAMP receptor protein

cAMP receptor protein is a regulatory protein in bacteria. This protein binds Cyclic adenosine monophosphate, which causes a conformational change that allows the protein to bind tightly to a specific DNA sequence in the promoters of the genes it controls....
 (CRP) also called: CAP (Catabolite gene Activator Protein) 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 enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
s that can supply energy independent of glucose.

An example of cAMP's function is the positive regulation of the lac operon
Lac operon

The lac operon is an operon required for the transport and metabolism of lactose in Escherichia coli and some other enteric bacteria. It consists of three adjacent structural genes, a promoter, a terminator , and an operator ....
. In an environment of a low glucose concentration, cAMP accumulates and binds to the allosteric site on CRP (cAMP receptor protein
CAMP receptor protein

cAMP receptor protein is a regulatory protein in bacteria. This protein binds Cyclic adenosine monophosphate, which causes a conformational change that allows the protein to bind tightly to a specific DNA sequence in the promoters of the genes it controls....
), a transcription activator protein. The protein assumes its active shape and binds to a specific site upstream of 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 some slime molds
In the species Dictyostelium discoideum
Dictyostelid

The dictyostelids are a group of cellular slime molds, or social amoebae. When food, normally bacteria, is readily available they are individual amoebae, which feed and divide normally....
 specifically, the chemotactic
Chemotaxis

Chemotaxis, a kind of taxis, is the phenomenon in which bodily cells, bacterium, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment....
 movement of 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.

Pathology


Role of cAMP in human carcinoma
Carcinoma

A carcinoma is any malignant cancer that arises from Epithelium. Carcinomas invade surrounding tissues and organs and may Metastasis, or spread, to lymph nodes and other sites....
 

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.

Role of cAMP in Prefrontal Cortex Disorders

Recent research may indicate that cAMP affects the function of higher order thinking in the prefrontal cortex
Prefrontal cortex

The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the primary motor cortex and premotor cortex areas....
 through its regulation of ion channels called hyperpolarization-activated cyclic nucleotide-gated channels (HCN). When cAMP stimulates the HCN, these gates open, rendering the brain cell closed to communication, thus interfering with prefrontal cortex
Prefrontal cortex

The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the primary motor cortex and premotor cortex areas....
 function. This research is of interest to scientists studying the brain, especially the degradation of higher cognitive function in ADHD and aging.

See also


  • Cyclic guanosine monophosphate
    Cyclic guanosine monophosphate

    Cyclic guanosine monophosphate is a cyclic nucleotide derived from guanosine triphosphate . cGMP acts as a second messenger much like cyclic AMP, most notably by activating intracellular protein kinases in response to the binding of cell membrane-impermeable peptide hormones to the external cell surface....
     (cGMP)
  • Acrasin
    Acrasin

    Acrasin a chemotactic chemical secreted by cellular Slime molds to signal that many Myxamoebae should come together to form an aggregate Pseudoplasmodium....
     Specific to chemotactic use in Dictyostelium discoideum.
  • cAMP dependent pathway
    CAMP dependent pathway

    In the field of molecular biology, the cAMP dependent pathway, also known as the adenylate cyclase pathway, is a G protein-coupled receptor triggered signal transduction used in cell communication....


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