Talk:Pyruvate kinase

message: I want to test a template...  --Dan|(talk) 15:10, 3 June 2006 (UTC)
thread_title:  Template Testing 

message: Wild type is refrecne to the genes that produce the enzyme so when you say wild type you mean in a health indivdual. i dont belive this to be correct and if it is , it should be  ellbarated on alittle  —Preceding unsigned comment added by 131.227.105.67 (talk) 10:26, 28 May 2010 (UTC)
thread_title:  wild type condition 

message: Can someone reference the statement that pyruvate kinase requires manganese ion (Mn)?
As in Voet Biochemistry text book 3rd edition on pp584, it says Mg2+ and K+. Otivaeey (talk) 19:14, 13 February 2011 (UTC)
thread_title:  Cofactors of pyruvate kinase 

message: Can someone add on about where the extra H in pyruvate comes from? It doesn't seem like from water. I think this is always a vague point in this particular reaction analysis of glycolysis pathway.  — Preceding unsigned comment added by Otivaeey (talk • contribs) 19:09, 13 February 2011 (UTC)
thread_title:  Missing link of addition of hydrogen from PEP to Pyruvate 

message: Hi! I am taking a biochemistry class at UCLA and I have picked this page to update. I have created the following outline for the direction I plan to take on this page. Please let me know if you have any advice, comments, suggestions, etc. 
 Topic Outline: 
Introduction: 
 Expand on this section, not enough written 
 Include more about its structure: tetrameter, 4 metal binding sites, etc. Gupta, V. and Bamezai, R. N.K. (2010), Human pyruvate kinase M2: A multifunctional protein. Protein Science, 19: 2031–2044. doi:10.1002/pro.505  "Pyruvate Kinase - Worthington Enzyme Manual". www.worthington-biochem.com. Retrieved 2016-05-05. 
Reaction:
 Leave mostly as it is, not much more information here
 Reverse Reaction:
 Gluconeogenesis:
 Add in a bit more detail as well Rognstad, R.; Katz, J. (1977-03-25). "Role of pyruvate kinase in the regulation of gluconeogenesis from L-lactate.". Journal of Biological Chemistry 252 (6): 1831–1833. ISSN 0021-9258. .
 Hormonal Control Feliú, J. E.; Hue, L.; Hers, H. G. (1976-08-01). "Hormonal control of pyruvate kinase activity and of gluconeogenesis in isolated hepatocytes". Proceedings of the National Academy of Sciences 73 (8): 2762–2766. ISSN 0027-8424. PMC 430732. .
 Effect of Metaformin  Argaud, Doriane; Roth, Hubert; Wiernsperger, Nicolas; Leverve, Xavier M. (1993-05-01). "Metformin decreases gluconeogenesis by enhancing the pyruvate kinase flux in isolated rat hepatocytes". European Journal of Biochemistry 213 (3): 1341–1348. doi:10.1111/j.1432-1033.1993.tb17886.x. ISSN 1432-1033.
 Regulation in Yeast  Gancedo, J M; Gancedo, C; Sols, A (1967-02-01). "Regulation of the concentration or activity of pyruvate kinase in yeasts and its relationship to gluconeogenesis.". Biochemical Journal 102 (2): 23C–25C. ISSN 0264-6021. PMC 1270297. .
Properties and Characteristics:
 PKLR Gene:
 Mutations Canu, Giulia; De Bonis, Maria; Minucci, Angelo; Capoluongo, Ettore (2016-03-01). "Red blood cell PK deficiency: An update of PK-LR gene mutation database". Blood Cells, Molecules, and Diseases 57: 100–109. doi:10.1016/j.bcmd.2015.12.009
 Isozymes in Vertebrates:Hall, Elizabeth R.; Larry Cottam, G. (1978-01-01). "Isozymes of pyruvate kinase in vertebrates: their physical, chemical, kinetic and immunological properties". International Journal of Biochemistry 9 (11): 785–794. doi:10.1016/0020-711X(78)90027-7
 In Cats Stuart, David I.; Levine, Michael; Muirhead, Hilary; Stammers, David K. (1979-10-15). "Crystal structure of cat muscle pyruvate kinase at a resolution of 2.6 Å". Journal of Molecular Biology 134 (1): 109–142. doi:10.1016/0022-2836(79)90416-9.
 In Pigs Berglund, L.; Ljungström, O.; Engström, L. (1977-09-10). "Purification and characterization of pig kidney pyruvate kinase (type A).". Journal of Biological Chemistry 252 (17): 6108–6111. ISSN 0021-9258. .
 In Rat:
 Liver, Two types found Tanaka, Takehiko; Harano, Yutaka; Morimura, Hiroko; Mori, Ryosuke (1965-10-08). "Evidence for the presence of two types of pyruvate kinase in rat liver". Biochemical and Biophysical Research Communications 21 (1): 55–60. doi:10.1016/0006-291X(65)90425-0
Regulation:
 Already pretty thorough, fix it up a little bit and add some more detail  "Regulation of Glycolysis:". cmgm.stanford.edu. Retrieved 2016-05-05.
 In rat liver Titanji, Vincent P. K.; Zetterqvist, Örjan; Engström, Lorentz (1976-01-23). "Regulation in vitro of rat liver pyruvate kinase by phosphorylation-dephosphorylation reactions, catalyzed by cyclic-AMP dependent protein kinases and a histone phosphatase". Biochimica et Biophysica Acta (BBA) - Enzymology 422 (1): 98–108. doi:10.1016/0005-2744(76)90011-5  Blair, J. B.; Cimbala, M. A.; Foster, J. L.; Morgan, R. A. (1976-06-25). "Hepatic pyruvate kinase. Regulation by glucagon, cyclic adenosine 3'-5'-monophosphate, and insulin in the perfused rat liver.". Journal of Biological Chemistry 251 (12): 3756–3762. ISSN 0021-9258. .
 Carbohydrate response element binding protein Kawaguchi, Takumi; Takenoshita, Makoto; Kabashima, Tsutomu; Uyeda, Kosaku (2001-11-20). "Glucose and cAMP regulate the L-type pyruvate kinase gene by phosphorylation/dephosphorylation of the carbohydrate response element binding protein". Proceedings of the National Academy of Sciences 98 (24): 13710–13715. doi:10.1073/pnas.231370798. ISSN 0027-8424. PMC 61106. .
Inhibition:
 Inhibit by Oxygen Reactive Species (ROS)Anastasiou, Dimitrios; Poulogiannis, George; Asara, John M.; Boxer, Matthew B.; Jiang, Jian-kang; Shen, Min; Bellinger, Gary; Sasaki, Atsuo T.; Locasale, Jason W. (2011-12-02). "Inhibition of Pyruvate Kinase M2 by Reactive Oxygen Species Contributes to Cellular Antioxidant Responses". Science 334 (6060): 1278–1283. doi:10.1126/science.1211485. ISSN 0036-8075. PMC 3471535. .
 Inhibit by Phenylalanine and Phenylpyruvate Weber, George (1969-08-01). "Inhibition of Human Brain Pyruvate Kinase and Hexokinase by Phenylalanine and Phenylpyruvate: Possible Relevance to Phenylketonuric Brain Damage". Proceedings of the National Academy of Sciences 63 (4): 1365–1369. ISSN 0027-8424. PMC 223473. 
 Feedforward and Feedback Inhibition in Liver Tanaka, Takehiko; Sue, Fumiaki; Morimura, Hiroko (1967-11-17). "Feed-forward activation and feed-back inhibition of pyruvate kinase type L of rat liver". Biochemical and Biophysical Research Communications 29 (3): 444–449. doi:10.1016/0006-291X(67)90477-9.
Clinical Applications: (make sure to use review articles, not primary sources)
 Metabolism and Cancer Research: 
 In e. Coli Emmerling, Marcel; Dauner, Michael; Ponti, Aaron; Fiaux, Jocelyne; Hochuli, Michel; Szyperski, Thomas; Wüthrich, Kurt; Bailey, J. E.; Sauer, Uwe (2002-01-01). "Metabolic Flux Responses to Pyruvate Kinase Knockout in Escherichia coli". Journal of Bacteriology 184 (1): 152–164. doi:10.1128/JB.184.1.152-164.2002. ISSN 0021-9193. PMC 134756. 
 M2 Splice isoform  Christofk, Heather R.; Heiden, Matthew G. Vander; Harris, Marian H.; Ramanathan, Arvind; Gerszten, Robert E.; Wei, Ru; Fleming, Mark D.; Schreiber, Stuart L.; Cantley, Lewis C. "The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth". Nature 452 (7184): 230–233. doi:10.1038/nature06734 Christofk, Heather R.; Heiden, Matthew G. Vander; Wu, Ning; Asara, John M.; Cantley, Lewis C. "Pyruvate kinase M2 is a phosphotyrosine-binding protein". Nature 452 (7184): 181–186. doi:10.1038/nature06667.
 Redox Metabolism in Respiring Cells  Grüning, Nana-Maria; Rinnerthaler, Mark; Bluemlein, Katharina; Mülleder, Michael; Wamelink, Mirjam M. C.; Lehrach, Hans; Jakobs, Cornelis; Breitenbach, Michael; Ralser, Markus (2011-09-07). "Pyruvate Kinase Triggers a Metabolic Feedback Loop that Controls Redox Metabolism in Respiring Cells". Cell Metabolism 14 (3): 415–427. doi:10.1016/j.cmet.2011.06.017. ISSN 1550-4131. PMC 3202625.  21907146, 21907146
 Parasitic Disease: University of Edinburgh. "Enzyme discovery paves way to tackling deadly parasite diseases." ScienceDaily. ScienceDaily, 24 September 2014. <www.sciencedaily.com/releases/2014/09/140924113655.htm>
 Deficiency:
 Review of the last decade Grace, Rachael F.; Zanella, Alberto; Neufeld, Ellis J.; Morton, D. Holmes; Eber, Stefan; Yaish, Hassan; Glader, Bertil (2015-09-01). "Erythrocyte pyruvate kinase deficiency: 2015 status report". American Journal of Hematology 90 (9): 825–830. doi:10.1002/ajh.24088. ISSN 1096-8652. 
 Mutations Climent, Fernando; Roset, Feliu; Repiso, Ada; Pérez de la Ossa, Pablo (2009-06-01). "Red cell glycolytic enzyme disorders caused by mutations: an update". Cardiovascular & Hematological Disorders Drug Targets 9 (2): 95–106. ISSN 2212-4063. .
 Progress of Molecular Genetics Miwa, Shiro; Kanno, Hitoshi; Fujii, Hisaichi (1993-01-01). "Pyruvate kinase deficiency: Historical perspective and recent progress of molecular genetics". American Journal of Hematology 42 (1): 31–35. doi:10.1002/ajh.2830420108. ISSN 1096-8652.
 Methicillin-resistant Staphylococcus aureus: Kumar, Nag S.; Dullaghan, Edie M.; Finlay, B. Brett; Gong, Huansheng; Reiner, Neil E.; Jon Paul Selvam, J.; Thorson, Lisa M.; Campbell, Sara; Vitko, Nicholas (2014-03-01). "Discovery and optimization of a new class of pyruvate kinase inhibitors as potential therapeutics for the treatment of methicillin-resistant Staphylococcus aureus infections". Bioorganic & Medicinal Chemistry 22 (5): 1708–1725. doi:10.1016/j.bmc.2014.01.020.
Assay:
 Briefly Mention and Discuss  "Pyruvate Kinase - Assay". www.worthington-biochem.com. Retrieved 2016-05-05.  — Preceding unsigned comment added by Jlivschitz12 (talk • contribs) 11:54, 5 May 2016 (UTC)
thread_title:  Outline for New Edits 

message: Hi! I am taking a biochemistry course at UCLA and wish to add discussions about how pyruvate cancer is involved in cancer. Does anyone have any thoughts or suggestions?
Thanks Tkadali (talk) 05:24, 13 February 2019 (UTC)
thread_title:  Adding cancer related content to this page 

message: The section on Glycolysis/Regulation states that Pyruvate Kinase is rate-limiting. I don't think it is, at least not in mammalian cells, see the paper "Tanner et al, Four Key Steps Control Glycolytic Flux in Mammalian Cells, 2018, Cell Systems". Table 1 in the paper shows that PK (PKM1) has a flux control coefficient of less than 0.1, not exactly limiting. PKM2 is not limiting at all. I've not looked at yeast data or other organisms where PK might well have a higher flux control coefficient. This should be clarified in the text especially given the number of students that are likely to read this page. Rhodydog (talk) 18:20, 28 January 2021 (UTC)
thread_title:  PK is not Rate-Limiting in Mammalian Cells