:Adenosine monophosphate

{{chembox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 477242440

| ImageFile = Adenosinmonophosphat protoniert.svg

| ImageSize = 200px

| ImageName = Skeletal formula of AMP

| ImageFile1 = Adenosine-monophosphate-anion-3D-balls.png

| ImageSize1 = 200px

| ImageName1 = Ball-and-stick model of AMP

| IUPACName = 5′-Adenylic acid

| SystematicName = [(2R,3S,4R,5R)-5-(6-Amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate

| OtherNames = Adenosine 5'-monophosphate
Vitamin B8 {{cite web |title=Depositor-Supplied Synonyms |url=https://pubchem.ncbi.nlm.nih.gov/compound/6083#section=Depositor-Supplied-Synonyms |website=PubChem |publisher=NCBI}}

|Section1={{Chembox Identifiers

| PubChem = 6083

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 5858

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 415SHH325A

| InChI = 1/C10H14N5O7P/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(22-10)1-21-23(18,19)20/h2-4,6-7,10,16-17H,1H2,(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1

| InChIKey = UDMBCSSLTHHNCD-KQYNXXCUBP

| SMILES1 = c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(O)O)O)O)N

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 752

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C10H14N5O7P/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(22-10)1-21-23(18,19)20/h2-4,6-7,10,16-17H,1H2,(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = UDMBCSSLTHHNCD-KQYNXXCUSA-N

| CASNo = 61-19-8

| CASNo_Ref = {{cascite|correct|CAS}}

| IUPHAR_ligand = 2455

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB00131

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 16027

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = C00020

| SMILES = O=P(O)(O)OC[C@H]3O[C@@H](n2cnc1c(ncnc12)N)[C@H](O)[C@@H]3O

| MeSHName = Adenosine+monophosphate

}}

|Section2={{Chembox Properties

| C=10 | H=14 | N=5 | O=7 | P=1

| MolarMass = 347.22 g/mol

| Appearance = white crystalline powder

| pKa = 0.9{{citation needed|date=September 2016}}, 3.8, 6.1

| Density = 2.32 g/mL

| MeltingPtC = 178 to 185

| BoilingPtC = 798.5

}}

|Section3={{Chembox Hazards

| MainHazards =

| FlashPt =

| AutoignitionPt =

}}

Adenosine monophosphate (AMP), also known as 5'-adenylic acid, is a nucleotide. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine. It is an ester of phosphoric acid and the nucleoside adenosine.{{cite web |title=Adenosine monophosphate (Compound) |url=https://pubchem.ncbi.nlm.nih.gov/compound/Adenosine-monophosphate |website=PubChem |publisher=NCBI |access-date=30 April 2020}} As a substituent it takes the form of the prefix adenylyl-.{{cite journal |title=Nomenclature of Carbohydrates: (Recommendations 1996) |journal=Journal of Carbohydrate Chemistry |date=1997 |volume=16 |issue=8 |pages=1191–1280 |doi=10.1080/07328309708005748}}

AMP plays an important role in many cellular metabolic processes, being interconverted to adenosine triphosphate (ATP) and adenosine diphosphate (ADP), as well as allosterically activating enzymes such as myophosphorylase-b. AMP is also a component in the synthesis of RNA.{{cite journal | vauthors = Jauker M, Griesser H, Richert C | title = Spontaneous Formation of RNA Strands, Peptidyl RNA, and Cofactors | journal = Angewandte Chemie | volume = 54 | issue = 48 | pages = 14564–9 | date = November 2015 | pmid = 26435376 | pmc = 4678511 | doi = 10.1002/anie.201506593 }} AMP is present in all known forms of life.{{cite web |title=Adenosine monophosphate |url=https://hmdb.ca/metabolites/HMDB0000045 |website=The Human Metabolome Database |access-date=3 July 2020}}

Production and degradation

AMP does not have the high energy phosphoanhydride bond associated with ADP and ATP. AMP can be produced from ADP by the myokinase (adenylate kinase) reaction when the ATP reservoir in the cell is low:{{Cite journal |last1=Baker |first1=Julien S. |last2=McCormick |first2=Marie Clare |last3=Robergs |first3=Robert A. |date=2010 |title=Interaction among Skeletal Muscle Metabolic Energy Systems during Intense Exercise |journal=Journal of Nutrition and Metabolism |volume=2010 |pages=905612 |doi=10.1155/2010/905612 |issn=2090-0732 |pmc=3005844 |pmid=21188163 |doi-access=free }}{{Citation |last=Valberg |first=Stephanie J. |title=Chapter 15 - Skeletal Muscle Function |date=2008-01-01 |url=https://www.sciencedirect.com/science/article/pii/B9780123704917000155 |work=Clinical Biochemistry of Domestic Animals (Sixth Edition) |pages=459–484 |editor-last=Kaneko |editor-first=J. Jerry |access-date=2023-10-10 |place=San Diego |publisher=Academic Press |isbn=978-0-12-370491-7 |editor2-last=Harvey |editor2-first=John W. |editor3-last=Bruss |editor3-first=Michael L.}}

: 2 ADP → ATP + AMP

Or AMP may be produced by the hydrolysis of one high energy phosphate bond of ADP:

: ADP + H₂O → AMP + P_i

AMP can also be formed by hydrolysis of ATP into AMP and pyrophosphate:

: ATP + H₂O → AMP + PP_i

When RNA is broken down by living systems, nucleoside monophosphates, including adenosine monophosphate, are formed.

AMP can be regenerated to ATP as follows:

: AMP + ATP → 2 ADP (adenylate kinase in the opposite direction)

: ADP + P_i → ATP (this step is most often performed in aerobes by the ATP synthase during oxidative phosphorylation)

AMP can be converted into inosine monophosphate by the enzyme myoadenylate deaminase, freeing an ammonia group.

In a catabolic pathway, the purine nucleotide cycle, adenosine monophosphate can be converted to uric acid, which is excreted from the body in mammals.{{cite journal | vauthors = Maiuolo J, Oppedisano F, Gratteri S, Muscoli C, Mollace V | title = Regulation of uric acid metabolism and excretion | journal = International Journal of Cardiology | volume = 213 | pages = 8–14 | date = June 2016 | pmid = 26316329 | doi = 10.1016/j.ijcard.2015.08.109 | doi-access = free }}

Physiological role in regulation

= AMP-activated kinase regulation =

The eukaryotic cell enzyme 5' adenosine monophosphate-activated protein kinase, or AMPK, utilizes AMP for homeostatic energy processes during times of high cellular energy expenditure, such as exercise.{{cite journal | vauthors = Richter EA, Ruderman NB | title = AMPK and the biochemistry of exercise: implications for human health and disease | journal = The Biochemical Journal | volume = 418 | issue = 2 | pages = 261–75 | date = March 2009 | pmid = 19196246 | pmc = 2779044 | doi = 10.1042/BJ20082055 }} Since ATP cleavage, and corresponding phosphorylation reactions, are utilized in various processes throughout the body as a source of energy, ATP production is necessary to further create energy for those mammalian cells. AMPK, as a cellular energy sensor, is activated by decreasing levels of ATP, which is naturally accompanied by increasing levels of ADP and AMP.{{cite journal | vauthors = Carling D, Mayer FV, Sanders MJ, Gamblin SJ | title = AMP-activated protein kinase: nature's energy sensor | language = En | journal = Nature Chemical Biology | volume = 7 | issue = 8 | pages = 512–8 | date = July 2011 | pmid = 21769098 | doi = 10.1038/nchembio.610 }}

Though phosphorylation appears to be the main activator for AMPK, some studies suggest that AMP is an allosteric regulator as well as a direct agonist for AMPK.{{cite journal | vauthors = Faubert B, Vincent EE, Poffenberger MC, Jones RG | title = The AMP-activated protein kinase (AMPK) and cancer: many faces of a metabolic regulator | journal = Cancer Letters | volume = 356 | issue = 2 Pt A | pages = 165–70 | date = January 2015 | pmid = 24486219 | doi = 10.1016/j.canlet.2014.01.018 }} Furthermore, other studies suggest that the high ratio of AMP:ATP levels in cells, rather than just AMP, activate AMPK. For example, the AMP-activated kinases of Caenorhabditis elegans and Drosophila melanogaster were found to have been activated by AMP, while yeast and plant kinases were not allosterically activated by AMP.{{Cite journal|vauthors=Hardie DG|date=2011-09-15|title=AMP-activated protein kinase—an energy sensor that regulates all aspects of cell function|journal=Genes & Development|language=en|volume=25|issue=18|pages=1895–1908|doi=10.1101/gad.17420111|issn=0890-9369|pmid=21937710|pmc=3185962}}

AMP binds to the γ-subunit of AMPK, leading to the activation of the kinase, and then eventually a cascade of other processes such as the activation of catabolic pathways and inhibition of anabolic pathways to regenerate ATP. Catabolic mechanisms, which generate ATP through the release of energy from breaking down molecules, are activated by the AMPK enzyme while anabolic mechanisms, which utilize energy from ATP to form products, are inhibited.{{cite journal | vauthors = Hardie DG | title = Energy sensing by the AMP-activated protein kinase and its effects on muscle metabolism | journal = The Proceedings of the Nutrition Society | volume = 70 | issue = 1 | pages = 92–9 | date = February 2011 | pmid = 21067629 | doi = 10.1017/S0029665110003915 | doi-access = free }} Though the γ-subunit can bind AMP/ADP/ATP, only the binding of AMP/ADP results in a conformational shift of the enzyme protein. This variance in AMP/ADP versus ATP binding leads to a shift in the dephosphorylation state for the enzyme.{{cite journal | vauthors = Krishan S, Richardson DR, Sahni S | title = Adenosine monophosphate-activated kinase and its key role in catabolism: structure, regulation, biological activity, and pharmacological activation | journal = Molecular Pharmacology | volume = 87 | issue = 3 | pages = 363–77 | date = March 2015 | pmid = 25422142 | doi = 10.1124/mol.114.095810 | doi-access = free }} The dephosphorylation of AMPK through various protein phosphatases completely inactivates catalytic function. AMP/ADP protects AMPK from being inactivated by binding to the γ-subunit and maintaining the dephosphorylation state.{{cite journal | vauthors = Xiao B, Sanders MJ, Underwood E, Heath R, Mayer FV, Carmena D, Jing C, Walker PA, Eccleston JF, Haire LF, Saiu P, Howell SA, Aasland R, Martin SR, Carling D, Gamblin SJ | title = Structure of mammalian AMPK and its regulation by ADP | journal = Nature | volume = 472 | issue = 7342 | pages = 230–3 | date = April 2011 | pmid = 21399626 | pmc = 3078618 | doi = 10.1038/nature09932 | bibcode = 2011Natur.472..230X }}

cAMP

AMP can also exist as a cyclic structure known as cyclic AMP (or cAMP). Within certain cells the enzyme adenylate cyclase makes cAMP from ATP, and typically this reaction is regulated by hormones such as adrenaline or glucagon. cAMP plays an important role in intracellular signaling.{{Cite book|title=Metabolic Control|volume=233|last1=Ravnskjaer|first1=Kim|last2=Madiraju|first2=Anila|last3=Montminy|first3=Marc | name-list-style = vanc |date=2015|publisher=Springer, Cham|isbn=9783319298047|series=Handbook of Experimental Pharmacology|pages=29–49|doi=10.1007/164_2015_32|pmid = 26721678}} In skeletal muscle, cyclic AMP, triggered by adrenaline, starts a cascade (cAMP-dependent pathway) for the conversion of myophosphorylase-b into the phosphorylated form of myophoshorylase-a for glycogenolysis.{{Cite book |last=Coffee |first=Carole J. |title=Quick Look Medicine: Metabolism |publisher=Hayes Barton Press |year=1999 |isbn=1-59377-192-4}}{{Cite web |date=2022-01-01 |title=15.3: Glycogenolyis and its Regulation by Glucagon and Epinephrine Signaling |url=https://bio.libretexts.org/Bookshelves/Biochemistry/Fundamentals_of_Biochemistry_(Jakubowski_and_Flatt)/02%3A_Unit_II-_Bioenergetics_and_Metabolism/15%3A_Glucose_Glycogen_and_Their_Metabolic_Regulation/15.03%3A_15.3_Glycogenolyis_and_its_Regulation_by_Glucagon_and_Epinephrine_Signaling |access-date=2023-10-10 |website=Biology LibreTexts |language=en}}