Editing Pyruvate kinase (section)

=== Allosteric effectors ===
[[Allosteric regulation]] is the binding of an effector to a site on the protein other than the active site, causing a conformational change and altering the activity of that given protein or enzyme. Pyruvate kinase has been found to be allosterically activated by FBP and allosterically inactivated by ATP and alanine.<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 = 148–56 | date = August 1973 | pmid = 4729424 | doi = 10.1111/j.1432-1033.1973.tb02969.x | hdl-access = free | hdl = 10261/78345 }}</ref> Pyruvate Kinase tetramerization is promoted by FBP and Serine while tetramer dissociation is promoted by L-Cysteine.<ref>{{cite journal | vauthors = Yang J, Liu H, Liu X, Gu C, Luo R, Chen HF | title = Synergistic Allosteric Mechanism of Fructose-1,6-bisphosphate and Serine for Pyruvate Kinase M2 via Dynamics Fluctuation Network Analysis | journal = Journal of Chemical Information and Modeling | volume = 56 | issue = 6 | pages = 1184–1192 | date = June 2016 | pmid = 27227511 | pmc = 5115163 | doi = 10.1021/acs.jcim.6b00115 }}</ref><ref>{{cite journal | vauthors = Chaneton B, Hillmann P, Zheng L, Martin AC, Maddocks OD, Chokkathukalam A, Coyle JE, Jankevics A, Holding FP, Vousden KH, Frezza C, O'Reilly M, Gottlieb E | display-authors = 6 | title = Serine is a natural ligand and allosteric activator of pyruvate kinase M2 | journal = Nature | volume = 491 | issue = 7424 | pages = 458–462 | date = November 2012 | pmid = 23064226 | pmc = 3894725 | doi = 10.1038/nature11540 | bibcode = 2012Natur.491..458C }}</ref><ref>{{cite journal | vauthors = Nakatsu D, Horiuchi Y, Kano F, Noguchi Y, Sugawara T, Takamoto I, Kubota N, Kadowaki T, Murata M | display-authors = 6 | title = L-cysteine reversibly inhibits glucose-induced biphasic insulin secretion and ATP production by inactivating PKM2 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 10 | pages = E1067-76 | date = March 2015 | pmid = 25713368 | pmc = 4364213 | doi = 10.1073/pnas.1417197112 | bibcode = 2015PNAS..112E1067N | doi-access = free }}</ref>

==== Fructose-1,6-bisphosphate ====
FBP is the most significant source of regulation because it comes from within the glycolysis pathway. FBP is a glycolytic intermediate produced from the phosphorylation of [[fructose 6-phosphate]]. FBP binds to the allosteric binding site on domain C of pyruvate kinase and changes the conformation of the enzyme, causing the activation of pyruvate kinase activity.<ref>{{cite journal | vauthors = Ishwar A |title=Distinguishing the interactions in the fructose 1,6-bisphosphate binding site of human liver pyruvate kinase that contribute to allostery. |journal=Biochemistry |volume=54 |issue=7 |pages=1516–24 |date=24 February 2015 |pmid=25629396 |pmc=5286843 |doi=10.1021/bi501426w }}</ref> As an intermediate present within the glycolytic pathway, FBP provides [[feed forward (control)|feedforward stimulation]] because the higher the concentration of FBP, the greater the allosteric activation and magnitude of pyruvate kinase activity. Pyruvate kinase is most sensitive to the effects of FBP. As a result, the remainder of the regulatory mechanisms serve as secondary modification.<ref name="Valentini 18145–18152"/><ref>{{cite journal | vauthors = Jurica MS, Mesecar A, Heath PJ, Shi W, Nowak T, Stoddard BL | title = The allosteric regulation of pyruvate kinase by fructose-1,6-bisphosphate | journal = Structure | volume = 6 | issue = 2 | pages = 195–210 | date = February 1998 | pmid = 9519410 | doi = 10.1016/S0969-2126(98)00021-5 | doi-access = free }}</ref>