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.[3] AMP is present in all known forms of life.[4]
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.[8] 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.[9]
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.[10] Furthermore, other studies suggest that the high ratio of AMP:ATP levels in cells, rather than just AMP, activate AMPK.[11] 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.[11]
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.[12] 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.[13] 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.[14]
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.[15] 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.[16][17]
^Valberg, Stephanie J. (1 January 2008), Kaneko, J. Jerry; Harvey, John W.; Bruss, Michael L. (eds.), "Chapter 15 - Skeletal Muscle Function", Clinical Biochemistry of Domestic Animals (Sixth Edition), San Diego: Academic Press, pp. 459–484, ISBN978-0-12-370491-7, retrieved 10 October 2023
^Carling D, Mayer FV, Sanders MJ, Gamblin SJ (July 2011). "AMP-activated protein kinase: nature's energy sensor". Nature Chemical Biology. 7 (8): 512–8. doi:10.1038/nchembio.610. PMID21769098.
^Faubert B, Vincent EE, Poffenberger MC, Jones RG (January 2015). "The AMP-activated protein kinase (AMPK) and cancer: many faces of a metabolic regulator". Cancer Letters. 356 (2 Pt A): 165–70. doi:10.1016/j.canlet.2014.01.018. PMID24486219.
