Cyclic adenosine monophosphate

Structural formula
General
Surname	Cyclic adenosine monophosphate
other names	Adenosine 3 ′, 5 ′ monophosphate cyclic AMP cyclo-AMP cAMP ADENOSINE CYCLIC PHOSPHATE ( INCI )
Molecular formula	C 10 H 12 N 5 O 6 P
Brief description	colorless solid
External identifiers / databases
CAS number 60-92-4 EC number 200-492-9 ECHA InfoCard 100,000,448 PubChem 6076 ChemSpider 5851 DrugBank DB02527 Wikidata Q210041
properties
Molar mass	329.21 g · mol -1
Physical state	firmly
Melting point	260 ° C (decomposition)
solubility	bad in water
safety instructions
GHS labeling of hazardous substances danger H and P phrases H: 318-314 P: 301 + 330 + 331-280-305 + 351 + 338-310
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Cyclic adenosine monophosphate (cAMP) is a biochemically derived molecule from adenosine triphosphate (ATP) that serves as a second messenger in cellular signal transduction and in particular leads to the activation of many peptide hormones ( protein kinases ).

cAMP synthesis and degradation

The membrane-bound adenylyl cyclase is stimulated by activation of a G-protein-coupled receptor by a hormone (e.g. glucagon ), a neurotransmitter (e.g. noradrenaline ) or an odorous substance . This converts cellular ATP to cAMP. A well-known direct stimulator of adenylyl cyclase is forskolin .

The breakdown of cAMP to AMP ( adenosine monophosphate ) is catalyzed by some members of the phosphodiesterase enzyme group . Caffeine is an unselective inhibitor of this group of enzymes.

Functions

Activation of protein kinases

cAMP activates type A protein kinases (PKA). These lead to a variety of effects via phosphorylation of various cellular proteins, e.g. B .:

• Phosphorylation of Ca ²⁺ channels , which in turn causes them to open
• Phosphorylation of the myosin light chain kinase , which causes relaxation of the smooth muscles (This statement is no longer relevant. It has been shown in vitro that PKA reduce the Ca ²⁺ sensitivity of the smooth muscles by inhibiting the myosin light chain kinase can, but it is questionable whether this mechanism is relevant in vivo)
• Phosphorylation of transcription factors such as B. CREB , which causes the transcription of cAMP-inducible genes

Activation of cAMP-regulated ion channels

In addition to cGMP, cAMP binds to a group of CNG ion channels that play an important role in the processing of olfactory signals.

Activation of EPAC

EPAC ( Exchange Protein activated by cAMP) are cAMP-binding proteins which, as EPAC / cAMP complexes, catalyze the exchange of GDP for GTP and thus directly activate small GTPases of the Ras family (Rap1 and Rap2), which leads to MAP -Kinases are activated.

Other functions of the complex include: a. on insulin secretion from the B cells of the pancreas.

Metabolic regulation

Activation of protein kinases regulates numerous metabolic functions. Examples are glycogen breakdown into glucose , lipolysis and the release of tissue hormones such as somatostatin .

cAMP in bacteria

cAMP can already be found in bacteria as a hunger signal (glucose deficiency signal ), but its mode of action here is completely different: the molecule is part of a glucose repression of the lactose utilization of the aforementioned control circuit.

If glucose (Glc) is present in the medium, the genes of the lactose operon ( lac operon ) are immobilized. This makes sense because the utilization of lactose (Lac) would be superfluous under these ideal conditions.

• It was found that the concentration of cAMP is low in the presence of Glc;
• After Glc withdrawal, however, it increases sharply due to the activation of a bacterial adenylyl cyclase (AC).
  • Under these conditions a Glc transport protein (TP) is phosphorylated (TP- P ). It forms a complex with AC and thereby activates it. If there was an excess of Glc, TP- P would be involved in the formation of glucose-6-phosphate (G-6 P ) through phosphate transfer and would lose its influence (as TP) on the AC.
• cAMP then binds to the CAP (catabolite activator protein), also known as CRP (cAMP receptor protein), which now activates the genes belonging to the lac operon as a transcription factor . This initiates the lactose intake under "starvation conditions".

Lactose operon: cAMP as a hunger signal in bacteria. To survive in glucose (Glc) deficiency situations, the bacterium ( Escherichia coli ) has a controllable gene unit ( operon ), which enables the uptake and utilization of lactose (Lac) if necessary. This process requires two signals:
1. In the case of Glc deficiency, cAMP activates the CAP protein, which binds directly to the promoter (p) and supports its activation;
2. Lac binds to a repressor protein (REP); this then separates from the operator sequence (o) and releases the transcription of the lacZYA gene unit.
When Glc is available, the cAMP level falls through inhibition of adenylyl cyclase (AC). The role of a glucose transport protein (TP) in this process is described in the text.

See also

• cyclic guanosine monophosphate (cGMP)

Individual evidence

1. ↑ Entry on ADENOSINE CYCLIC PHOSPHATE in the CosIng database of the EU Commission, accessed on March 30, 2020.
2. ↑ ^{a b} Entry on cyclic AMP. In: Römpp Online . Georg Thieme Verlag, accessed on September 29, 2014.
3. ↑ ^{a b c} Data sheet for cyclic adenosine monophosphate from Acros, accessed on January 21, 2016.
4. ↑ Robert F. Schmidt (editor), Florian Lang (editor), Manfred Heckmann (ed.): Physiologie des Menschen . Springer Berlin Heidelberg; 30th edition, (2007).
5. ↑ CNG channels . Jena University Hospital. Retrieved February 13, 2019.
6. ↑ Pingyuan Wang, Zhiqing Liu, Haiying Chen, Na Ye, Xiaodong Cheng, Jia Zhoua: Exchange proteins directly activated by cAMP (EPACs): Emerging therapeutic targets . In: Bioorganic & Medicinal Chemistry Letters . tape 27 , no. 8 , May 15, 2017, doi : 10.1016 / j.bmcl.2017.02.065 ( els-cdn.com [PDF; accessed on February 6, 2019]).