Editing Adenosine monophosphate (section)

=== AMP-activated kinase regulation ===
The eukaryotic cell enzyme [[AMP-activated protein kinase|5' adenosine monophosphate-activated protein kinase]], or AMPK, utilizes AMP for [[Homeostasis|homeostatic]] energy processes during times of high cellular energy expenditure, such as exercise.<ref>{{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 }}</ref> 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.<ref>{{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 }}</ref>

Though phosphorylation appears to be the main [[Enzyme activator|activator]] for AMPK, some studies suggest that AMP is an [[Allosteric regulation|allosteric regulator]] as well as a [[Agonist|direct agonist]] for AMPK.<ref>{{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 }}</ref> Furthermore, other studies suggest that the high ratio of AMP:ATP levels in cells, rather than just AMP, activate AMPK.<ref name=Hardie2011/> 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.<ref name=Hardie2011>{{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}}</ref>

AMP binds to the ''γ''-subunit of AMPK, leading to the activation of the kinase, and then eventually a [[Cascade reaction|cascade]] of other processes such as the activation of [[Catabolism|catabolic]] pathways and [[Enzyme inhibitor|inhibition]] of [[Anabolism|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.<ref>{{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 }}</ref> 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.<ref>{{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 }}</ref> The dephosphorylation of AMPK through various protein [[phosphatase]]s completely inactivates catalytic function. AMP/ADP protects AMPK from being inactivated by binding to the ''γ''-subunit and maintaining the dephosphorylation state.<ref>{{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 }}</ref>