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Revision as of 16:24, 9 January 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{chembox}} taken from revid 469941559 of page Cyclic_adenosine_monophosphate for the Chem/Drugbox validation project (updated: '').		Latest revision as of 12:50, 27 December 2024 edit Д.Ильин (talk | contribs)Extended confirmed users600 edits img
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			{{Short description|Cellular second messenger}}
	{{ambox | text = This page contains a copy of the infobox ({{tl|chembox}}) taken from revid of page ] with values updated to verified values.}}
	{{chembox		{{Chembox
			| Watchedfields = changed
	| verifiedrevid = 443545451		| verifiedrevid = 476994238
⚫	| ImageFileL1 = Cyclic-adenosine-monophosphate-2D-skeletal.png
	| ImageSizeL1 = 150 px		| ImageFile1 = CAMP.svg
			| ImageClass1 = skin-invert-image
	| ImageFileR1 = Cyclic-adenosine-monophosphate-3D-balls.png
		⚫	| ImageFile2 = Cyclic-adenosine-monophosphate-from-xtal-3D-bs-17.png
	| ImageSizeR1 = 150 px
	| IUPACName =		| IUPACName = Adenosine 3′,5′-(hydrogen phosphate)
			| SystematicName = (4a''R'',6''R'',7''R'',7a''S'')-6-(6-Amino-9''H''-purin-9-yl)-2,7-dihydroxytetrahydro-2''H'',4''H''-2λ<sup>5</sup>-furodioxaphosphinin-2-one
	| OtherNames =		| OtherNames =
	| Section1 = {{Chembox Identifiers		| Section1 = {{Chembox Identifiers
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 5851		| ChemSpiderID = 5851
	| ChEMBL_Ref = {{ebicite|correct|EBI}}		| ChEMBL_Ref = {{ebicite|correct|EBI}}
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	| StdInChIKey = IVOMOUWHDPKRLL-KQYNXXCUSA-N		| StdInChIKey = IVOMOUWHDPKRLL-KQYNXXCUSA-N
	| CASNo = 60-92-4		| CASNo = 60-92-4
	| CASNo_Ref = {{cascite|correct|CAS}}		| CASNo_Ref = {{cascite|correct|CAS}}
	| PubChem = 6076		| PubChem = 6076
	| IUPHAR_ligand = 2352		| IUPHAR_ligand = 2352
	| DrugBank_Ref = {{drugbankcite|correct|drugbank}}		| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
	| DrugBank = DB02527		| DrugBank = DB02527
	| ChEBI_Ref = {{ebicite|correct|EBI}}		| ChEBI_Ref = {{ebicite|correct|EBI}}
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	| KEGG = C00575		| KEGG = C00575
	| SMILES = c1nc(c2c(n1)n(cn2)3(4(O3)COP(=O)(O4)O)O)N		| SMILES = c1nc(c2c(n1)n(cn2)3(4(O3)COP(=O)(O4)O)O)N
	| MeSHName = Cyclic+AMP		| MeSHName = Cyclic+AMP
	}}		}}
	| Section2 = {{Chembox Properties		| Section2 = {{Chembox Properties
	| Formula = C<sub>10</sub>H<sub>12</sub>N<sub>5</sub>O<sub>6</sub>P		| Formula = C<sub>10</sub>H<sub>11</sub>N<sub>5</sub>O<sub>6</sub>P
	| MolarMass = 329.206		| MolarMass = 329.206 g/mol
	| Appearance =		| Appearance =
	| Density =		| Density =
	| MeltingPt =		| MeltingPt =
	| BoilingPt =		| BoilingPt =
	}}		}}
	| Section3 = {{Chembox Hazards		| Section3 = {{Chembox Hazards
	| Solubility =		| MainHazards =
	| MainHazards =		| FlashPt =
	| FlashPt =		| AutoignitionPt =
	| Autoignition =
	}}		}}
	}}		}}
			]
			]]]
			'''Cyclic adenosine monophosphate''' ('''cAMP''', '''cyclic AMP''', or '''3',5'-cyclic ]''') is a ], or cellular signal occurring within cells, that is important in many biological processes. cAMP is a derivative of ] (ATP) and used for intracellular ] in many different organisms, conveying the ].
			{{toclimit}}
			==History==
			] of ] won a ] in 1971 "for his discoveries concerning the mechanisms of the action of hormones", especially epinephrine, via ]s (such as cyclic adenosine monophosphate, cyclic AMP).
			==Synthesis==
			The synthesis of cAMP is stimulated by trophic hormones that bind to receptors on cell surface. cAMP levels reach maximal levels within minutes and decrease gradually over an hour in cultured cells.<ref name="1990-Hanukoglu">{{cite journal |vauthors=Hanukoglu I, Feuchtwanger R, Hanukoglu A |title=Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells |journal=J Biol Chem |volume=265 |issue=33 |pages=20602–8 |date=November 1990 |pmid=2173715 |doi=10.1016/S0021-9258(17)30545-8 |url=}}</ref>
			Cyclic ] is synthesized from ] by ] located on the inner side of the plasma membrane and anchored at various locations in the interior of the cell.<ref>{{cite journal | vauthors = Rahman N, Buck J, Levin LR | date = November 2013 | title = pH sensing via bicarbonate-regulated "soluble" adenylate cyclase (sAC) | journal = Front Physiol | volume = 4 | page = 343 | pmid = 24324443 | pmc=3838963 | doi=10.3389/fphys.2013.00343| doi-access = free }}</ref> Adenylate cyclase is ''activated'' by a range of signaling molecules through the activation of adenylate cyclase stimulatory G (])-protein-coupled receptors. Adenylate cyclase is ''inhibited'' by agonists of adenylate cyclase inhibitory G (])-protein-coupled receptors. Liver adenylate cyclase responds more strongly to glucagon, and muscle adenylate cyclase responds more strongly to adrenaline.
			cAMP decomposition into ] is catalyzed by the enzyme ].
			==Functions==
			cAMP is a ], used for intracellular signal transduction, such as ] into cells the effects of ]s like ] and ], which cannot pass through the plasma membrane. It is also involved in the activation of ]s. In addition, cAMP ] and regulates the function of ] such as the ]s and a few other ] such as ] and ].
			===Role in eukaryotic cells===
			{{Main|function of cAMP-dependent protein kinase}}
			cAMP is associated with kinases function in several biochemical processes, including the regulation of ], ], and ] ].<ref>{{cite journal |vauthors=Ali ES, Hua J, Wilson CH, Tallis GA, Zhou FH, Rychkov GY, Barritt GJ |title=The glucagon-like peptide-1 analogue exendin-4 reverses impaired intracellular Ca2+ signalling in steatotic hepatocytes |journal=Biochimica et Biophysica Acta (BBA) - Molecular Cell Research |doi=10.1016/j.bbamcr.2016.05.006 |pmid=27178543 |volume=1863 |year=2016 |issue=9 |pages=2135–46|doi-access=free }}</ref>
			In eukaryotes, cyclic AMP works by activating protein kinase A (PKA, or ]). PKA is normally inactive as a tetrameric ], consisting of two ] and two regulatory units (C<sub>2</sub>R<sub>2</sub>), 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 enabling those catalytic units to ] substrate proteins.
			The active subunits catalyze the transfer of phosphate from ATP to specific ] or ] 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 increases in transcription. Not all protein kinases respond to cAMP. Several classes of ]s, including protein kinase C, are not cAMP-dependent.
			Further effects mainly depend on ], which vary based on the type of cell.
			Still, there are some minor PKA-independent functions of cAMP, e.g., activation of ]s, providing a minor pathway by which ] causes a release of ].
			However, the view that the majority of the effects of cAMP are controlled by PKA is an outdated one. In 1998 a family of cAMP-sensitive proteins with ] (GEF) activity was discovered. These are termed Exchange proteins activated by cAMP (Epac) and the family comprises ] and ].<ref>{{cite journal|last1=Bos|first1=Johannes L.|title=Epac proteins: multi-purpose cAMP targets|journal=Trends in Biochemical Sciences|date=December 2006|volume=31|issue=12|pages=680–686|doi=10.1016/j.tibs.2006.10.002|pmid=17084085}}</ref> The mechanism of activation is similar to that of PKA: the GEF domain is usually masked by the N-terminal region containing the cAMP binding domain. When cAMP binds, the domain dissociates and exposes the now-active GEF domain, allowing Epac to activate small Ras-like GTPase proteins, such as ].
			====Additional role of secreted cAMP in social amoebae====
			{{See also|Fungal behavior}}
			In the species '']'', cAMP acts outside the cell as a secreted signal. The ] aggregation of cells is organized by periodic waves of cAMP that propagate between cells over distances as large as several centimetres. 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.<ref>{{Cite book|last=Anderson|first=Peter A. V.|url=https://books.google.com/books?id=vEYGCAAAQBAJ&q=In+the+species+Dictyostelium+discoideum,+cAMP+acts+outside+the+cell+as+a+secreted+signal.+The+chemotactic+aggregation+of+cells+is+organized+by+periodic+waves+of+cAMP+that+propagate+between+cells+over+distances+as+large+as+several+centimetres.+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|title=Evolution of the First Nervous Systems|date=2013-11-11|publisher=Springer Science & Business Media|isbn=978-1-4899-0921-3|language=en}}</ref>
			=== Role in bacteria ===
			In ], 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, ], as a side-effect of glucose transport into the cell. The transcription factor ] (CRP) also called ] 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 ]s that can supply energy independent of glucose.
			cAMP, for example, is involved in the positive regulation of the ]. In an environment with a low glucose concentration, cAMP accumulates and binds to the allosteric site on CRP (]), 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.
			==Pathology==
			Since cyclic AMP is a second messenger and plays vital role in cell signalling, it has been implicated in various disorders but not restricted to the roles given below:
			=== Role 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.<ref>{{cite journal| url = http://cancerres.aacrjournals.org/cgi/content/full/64/4/1338| title = American Association for Cancer Research (cAMP-responsive Genes and Tumor Progression)| journal = Cancer Research| date = 15 February 2004| volume = 64| issue = 4| pages = 1338–1346| doi = 10.1158/0008-5472.CAN-03-2089| last1 = Abramovitch| first1 = Rinat| last2 = Tavor| first2 = Einat| last3 = Jacob-Hirsch| first3 = Jasmine| last4 = Zeira| first4 = Evelyne| last5 = Amariglio| first5 = Ninette| last6 = Pappo| first6 = Orit| last7 = Rechavi| first7 = Gideon| last8 = Galun| first8 = Eithan| last9 = Honigman| first9 = Alik| pmid = 14973073| s2cid = 14047485}}</ref><ref>{{cite journal| url = http://cancerres.aacrjournals.org/cgi/content/abstract/66/19/9483| title = American Association for Cancer Research (cAMP Dysregulation and Melonoma)| journal = Cancer Research| date = October 2006| volume = 66| issue = 19| pages = 9483–9491| doi = 10.1158/0008-5472.CAN-05-4227| last1 = Dumaz| first1 = Nicolas| last2 = Hayward| first2 = Robert| last3 = Martin| first3 = Jan| last4 = Ogilvie| first4 = Lesley| last5 = Hedley| first5 = Douglas| last6 = Curtin| first6 = John A.| last7 = Bastian| first7 = Boris C.| last8 = Springer| first8 = Caroline| last9 = Marais| first9 = Richard| pmid = 17018604| doi-access = free}}</ref><ref>{{cite journal| url = http://clincancerres.aacrjournals.org/cgi/content/abstract/2/1/201| title = American Association for Cancer Research (cAMP-binding Proteins' Presence in Tumors)| journal = Clinical Cancer Research| date = January 1996| volume = 2| issue = 1| pages = 201–206| last1 = Simpson| first1 = B. J.| last2 = Ramage| first2 = A. D.| last3 = Hulme| first3 = M. J.| last4 = Burns| first4 = D. J.| last5 = Katsaros| first5 = D.| last6 = Langdon| first6 = S. P.| last7 = Miller| first7 = W. R.}}</ref>
			=== Role in prefrontal cortex disorders ===
			Recent research suggests that cAMP affects the function of higher-order thinking in the ] through its regulation of ion channels called ] (HCN). When cAMP stimulates the HCN, the channels open, This research, especially the cognitive deficits in age-related illnesses and ADHD, is of interest to researchers studying the brain.<ref>{{cite web| url = https://www.sciencedaily.com/releases/2007/04/070420143324.htm| title = ScienceDaily ::Brain Networks Strengthened By Closing Ion Channels, Research Could Lead To ADHD Treatment }}</ref>
			cAMP is involved in activation of trigeminocervical system leading to neurogenic inflammation and causing migraine. <ref>{{cite journal |last1=Segatto |first1=Marco |title=Neurogenic Inflammation: The Participant in Migraine and Recent Advancements in Translational Research |journal=Biomedicines |year=2021 |volume=10 |issue=1 |page=76 |doi=10.3390/biomedicines10010076 |pmid=35052756 |pmc=8773152 |doi-access=free }}</ref>
			=== Role in infectious disease agents' pathogenesis ===
			Disrupted functioning of cAMP has been noted as one of the mechanisms of several bacterial exotoxins.
			They can be subgrouped into two distinct categories:<ref name="klin-wochenschr">{{cite journal |last1=Kather |first1=H |last2=Aktories |first2=K |date=November 15, 1983 |title=cAMP-System und bakterielle Toxine |url=https://pubmed.ncbi.nlm.nih.gov/6317939/ |journal=Klin Wochenschr |volume= 61|issue= 22|pages= 1109–1114| pmid=6317939 |doi=10.1007/BF01530837 |s2cid=33162709 |access-date=February 26, 2022}}</ref>
			* Toxins that interfere with enzymes ]s, and
			* ].
			==== ADP-ribosyl-transferases related toxins ====
			{{Main article|Cholera toxin}}
			* ] is an ] that has five B subunints and one A subunit. The toxin acts by the following mechanism: First, the B subunit ring of the cholera toxin binds to ] ]s on the surface of target cells. If a cell lacks GM1 the toxin most likely binds to other types of glycans, such as Lewis Y and Lewis X, attached to proteins instead of lipids.<ref>{{cite news |url=https://elifesciences.org/content/4/e09545 |title=Fucosylation and protein glycosylation create functional receptors for cholera toxin |author=Amberlyn M Wands |author2=Akiko Fujita |journal=eLife | date=October 2015 |volume=4 |doi=10.7554/eLife.09545 |doi-access=free }}</ref><ref>Cervin J, Wands AM, Casselbrant A, Wu H, Krishnamurthy S, Cvjetkovic A, et al. (2018) GM1 ganglioside-independent intoxication by Cholera toxin. PLoS Pathog 14(2): e1006862. https://doi.org/10.1371/journal.ppat.1006862</ref><ref>Fucosylated Molecules Competitively Interfere with Cholera Toxin Binding to Host Cells; Amberlyn M. Wands, Jakob Cervin, He Huang, Ye Zhang, Gyusaang Youn, Chad A. Brautigam, Maria Matson Dzebo, Per Björklund, Ville Wallenius, Danielle K. Bright, Clay S. Bennett, Pernilla Wittung-Stafshede, Nicole S. Sampson, Ulf Yrlid, and Jennifer J. Kohler; ACS Infectious Diseases Article ASAP, DOI: 10.1021/acsinfecdis.7b00085</ref><ref name="klin-wochenschr" />
			== Uses ==
			] is commonly used as a tool in biochemistry to raise levels of cAMP in the study and research of ] physiology.<ref>
			{{cite journal|last1=Alasbahi|first1=RH|last2=Melzig|first2=MF|title=Forskolin and derivatives as tools for studying the role of cAMP.|journal=Die Pharmazie|date=January 2012|volume=67|issue=1|pages=5–13|pmid=22393824}}</ref>
			== See also ==
			* ] (cGMP)
			* ] (8-Br-cAMP)
			* ] specific to chemotactic use in ''Dictyostelium discoideum''.
			* ] (PDE 4) which degrades cAMP
			==References==
			<references />
			{{Intracellular signaling peptides and proteins}}
			{{Nucleobases, nucleosides, and nucleotides}}
			{{DEFAULTSORT:Cyclic Adenosine Monophosphate}}
			]
			]
			]
			]