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==== Pyruvate kinase ==== [[File:Pyruvate Kinase 1A3W wpmp.png|thumb|right|[[Yeast]] [[pyruvate kinase]] ({{PDB|1A3W}})]] {{Main|Pyruvate kinase}} The final step of glycolysis is catalysed by pyruvate kinase to form pyruvate and another ATP. It is regulated by a range of different transcriptional, covalent and non-covalent regulation mechanisms, which can vary widely in different tissues.<ref>{{cite journal | vauthors = Carbonell J, Felíu JE, Marco R, Sols A | title = Pyruvate kinase. Classes of regulatory isoenzymes in mammalian tissues | journal = European Journal of Biochemistry | volume = 37 | issue = 1 | pages = 148–156 | date = August 1973 | pmid = 4729424 | doi = 10.1111/j.1432-1033.1973.tb02969.x | hdl = 10261/78345 | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Valentini G, Chiarelli L, Fortin R, Speranza ML, Galizzi A, Mattevi A | title = The allosteric regulation of pyruvate kinase | journal = The Journal of Biological Chemistry | volume = 275 | issue = 24 | pages = 18145–18152 | date = June 2000 | pmid = 10751408 | doi = 10.1074/jbc.m001870200 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Israelsen WJ, Vander Heiden MG | title = Pyruvate kinase: Function, regulation and role in cancer | journal = Seminars in Cell & Developmental Biology | volume = 43 | pages = 43–51 | date = July 2015 | pmid = 26277545 | pmc = 4662905 | doi = 10.1016/j.semcdb.2015.08.004 }}</ref> For example, in the liver, pyruvate kinase is regulated based on glucose availability. During fasting (no glucose available), [[glucagon]] activates [[protein kinase A]] which phosphorylates pyruvate kinase to inhibit it.<ref name=":4">{{cite journal | vauthors = Engström L | title = The regulation of liver pyruvate kinase by phosphorylation--dephosphorylation | journal = Current Topics in Cellular Regulation | volume = 13 | pages = 28–51 | date = 1978 | pmid = 208818 | doi = 10.1016/b978-0-12-152813-3.50006-9 | publisher = Elsevier | isbn = 978-0-12-152813-3 }}</ref> An increase in blood sugar leads to secretion of [[insulin]], which activates [[protein phosphatase 1]], leading to dephosphorylation and re-activation of pyruvate kinase.<ref name=":4" /> These controls prevent pyruvate kinase from being active at the same time as the enzymes that catalyze the reverse reaction ([[pyruvate carboxylase]] and [[phosphoenolpyruvate carboxykinase]]), preventing a [[futile cycle]].<ref name=":4" /> Conversely, the isoform of pyruvate kinasein found in muscle is not affected by protein kinase A (which is activated by adrenaline in that tissue), so that glycolysis remains active in muscles even during fasting.<ref name=":4" />
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