pyruvate kinase

Summary

Summary: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.

Top Publications

  1. Prasannan C, Villar M, Artigues A, Fenton A. Identification of regions of rabbit muscle pyruvate kinase important for allosteric regulation by phenylalanine, detected by H/D exchange mass spectrometry. Biochemistry. 2013;52:1998-2006 pubmed publisher
    ..of exchangeable backbone amide protons and the associated rate constants that are altered when rabbit muscle pyruvate kinase (rM1-PYK) binds either the allosteric inhibitor (phenylalanine) or a nonallosteric analogue of the inhibitor...
  2. Solomons J, Johnsen U, Schonheit P, Davies C. 3-Phosphoglycerate is an allosteric activator of pyruvate kinase from the hyperthermophilic archaeon Pyrobaculum aerophilum. Biochemistry. 2013;52:5865-75 pubmed publisher
    b>Pyruvate kinase (PK) is a highly regulated enzyme that catalyzes the final step of glycolysis...
  3. Deng Y, Olson D, Zhou J, Herring C, Joe Shaw A, Lynd L. Redirecting carbon flux through exogenous pyruvate kinase to achieve high ethanol yields in Clostridium thermocellum. Metab Eng. 2013;15:151-8 pubmed publisher
    In Clostridium thermocellum, a thermophilic anaerobic bacterium able to rapidly ferment cellulose to ethanol, pyruvate kinase (EC 2.7.1.40) is absent based on both the genome sequence and enzymatic assays...
  4. Keller K, Tan I, Lee Y. SAICAR stimulates pyruvate kinase isoform M2 and promotes cancer cell survival in glucose-limited conditions. Science. 2012;338:1069-72 pubmed publisher
    b>Pyruvate kinase isoform M2 (PKM2) plays an important role in the growth and metabolic reprogramming of cancer cells in stress conditions...
  5. Cunningham D, Liu Z, Domagalski N, Koepsel R, Ataai M, Domach M. Pyruvate kinase-deficient Escherichia coli exhibits increased plasmid copy number and cyclic AMP levels. J Bacteriol. 2009;191:3041-9 pubmed publisher
    Previously established consequences of abolishing pyruvate kinase (Pyk) activity in Escherichia coli during aerobic growth on glucose include reduced acetate production, elevated hexose monophosphate (HMP) pathway flux, elevated ..
  6. Benjaphokee S, Koedrith P, Auesukaree C, Asvarak T, Sugiyama M, Kaneko Y, et al. CDC19 encoding pyruvate kinase is important for high-temperature tolerance in Saccharomyces cerevisiae. N Biotechnol. 2012;29:166-76 pubmed publisher
    ..The gene CDC19, encoding pyruvate kinase, was cloned as the HTG2 gene...
  7. Ramay H, Vendelin M. Diffusion restrictions surrounding mitochondria: a mathematical model of heart muscle fibers. Biophys J. 2009;97:443-52 pubmed publisher
    ..Such a low level of permeability indicates that the proteins should play a dominant part in formation of the diffusion restrictions...
  8. Xu Y, Zhao X, Glass D, Absalan F, Perlman D, Broach J, et al. Regulation of yeast pyruvate kinase by ultrasensitive allostery independent of phosphorylation. Mol Cell. 2012;48:52-62 pubmed publisher
    ..Here we examine this issue, using as a case study the rapid decrease in pyruvate kinase flux in yeast upon glucose removal...
  9. Yu Z, Zhao X, Huang L, Zhang T, Yang F, Xie L, et al. Proviral insertion in murine lymphomas 2 (PIM2) oncogene phosphorylates pyruvate kinase M2 (PKM2) and promotes glycolysis in cancer cells. J Biol Chem. 2013;288:35406-16 pubmed publisher
    b>Pyruvate kinase M2 (PKM2) is a key player in the Warburg effect of cancer cells. However, the mechanisms of regulating PKM2 are not fully elucidated...

More Information

Publications90

  1. Martinez Balibrea E, Plasencia C, Ginés A, Martinez Cardus A, Musulen E, Aguilera R, et al. A proteomic approach links decreased pyruvate kinase M2 expression to oxaliplatin resistance in patients with colorectal cancer and in human cell lines. Mol Cancer Ther. 2009;8:771-8 pubmed publisher
    ..Mass spectrometry, Western blot, and real-time quantitative PCR confirmed the down-regulation of pyruvate kinase M2 (PK-M2) in HTOXAR3 cells...
  2. Tamada M, Suematsu M, Saya H. Pyruvate kinase M2: multiple faces for conferring benefits on cancer cells. Clin Cancer Res. 2012;18:5554-61 pubmed publisher
    The M2 splice isoform of pyruvate kinase (PKM2), an enzyme that catalyzes the later step of glycolysis, is a key regulator of aerobic glycolysis (known as the Warburg effect) in cancer cells...
  3. Zhao Y, Liu H, Riker A, Fodstad O, LeDoux S, Wilson G, et al. Emerging metabolic targets in cancer therapy. Front Biosci (Landmark Ed). 2011;16:1844-60 pubmed
    ..Here we provide an overview of the current understanding of the Warburg effect upon tumor cell growth and survival, and discussion on the potential metabolic targets for cancer therapy. ..
  4. Ye J, Mancuso A, Tong X, Ward P, Fan J, Rabinowitz J, et al. Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation. Proc Natl Acad Sci U S A. 2012;109:6904-9 pubmed publisher
    ..cancer cells display high glycolytic activity, cancer cells selectively express the less active M2 isoform of pyruvate kinase (PKM2)...
  5. Barrs V, Giger U, Wilson B, Chan C, Lingard A, Tran L, et al. Erythrocytic pyruvate kinase deficiency and AB blood types in Australian Abyssinian and Somali cats. Aust Vet J. 2009;87:39-44 pubmed publisher
    To determine the frequency of the mutant pyruvate kinase (PK) allele, haematological parameters and AB blood types of Abyssinian and Somali cats in Australia...
  6. Sun Q, Chen X, Ma J, Peng H, Wang F, Zha X, et al. Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth. Proc Natl Acad Sci U S A. 2011;108:4129-34 pubmed publisher
    ..For a largely unknown regulatory mechanism, a rate-limiting glycolytic enzyme pyruvate kinase M2 (PKM2) isoform is exclusively expressed in embryonic, proliferating, and tumor cells, and plays an ..
  7. Vander Heiden M, Locasale J, Swanson K, Sharfi H, Heffron G, Amador Noguez D, et al. Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science. 2010;329:1492-9 pubmed publisher
    ..The M2 isoform of pyruvate kinase (PKM2) promotes the metabolism of glucose by aerobic glycolysis and contributes to anabolic metabolism...
  8. Kefas B, Comeau L, Erdle N, Montgomery E, Amos S, Purow B. Pyruvate kinase M2 is a target of the tumor-suppressive microRNA-326 and regulates the survival of glioma cells. Neuro Oncol. 2010;12:1102-12 pubmed publisher
    ..Computational target gene prediction revealed pyruvate kinase type M2 (PKM2) as another target of miRNA-326...
  9. Anand P, Murali K, Tandon V, Murthy P, Chandra R. Insulinotropic effect of cinnamaldehyde on transcriptional regulation of pyruvate kinase, phosphoenolpyruvate carboxykinase, and GLUT4 translocation in experimental diabetic rats. Chem Biol Interact. 2010;186:72-81 pubmed publisher
    ..The treatment also showed a significant improvement in altered enzyme activities of pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK) and their mRNA expression levels...
  10. Luo W, Hu H, Chang R, Zhong J, Knabel M, O Meally R, et al. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell. 2011;145:732-44 pubmed publisher
    The pyruvate kinase isoforms PKM1 and PKM2 are alternatively spliced products of the PKM2 gene...
  11. Gao X, Wang H, Yang J, Chen J, Jie J, Li L, et al. Reciprocal regulation of protein kinase and pyruvate kinase activities of pyruvate kinase M2 by growth signals. J Biol Chem. 2013;288:15971-9 pubmed publisher
    b>Pyruvate kinase isoform M2 (PKM2) is an enzyme-catalyzing conversion of phosphoenolpyruvate to pyruvate in the glycolysis pathway...
  12. Shin Y, Yoo B, Hong Y, Chang H, Jung K, Jeong S, et al. Upregulation of glycolytic enzymes in proteins secreted from human colon cancer cells with 5-fluorouracil resistance. Electrophoresis. 2009;30:2182-92 pubmed publisher
    ..observed significant upregulation of glycolytic enzymes, including glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase M2 (PK-M2), transketolase, and NADP(+)-dependent malic enzyme 1...
  13. Berghout J, Higgins S, Loucoubar C, Sakuntabhai A, Kain K, Gros P. Genetic diversity in human erythrocyte pyruvate kinase. Genes Immun. 2012;13:98-102 pubmed publisher
    Previously, we have shown that pyruvate kinase, liver and red cell isoform (PKLR) deficiency protects mice in vivo against blood-stage malaria, and observed that reduced PKLR function protects human erythrocytes against Plasmodium ..
  14. Hardt P, Ewald N. Tumor M2 pyruvate kinase: a tumor marker and its clinical application in gastrointestinal malignancy. Expert Rev Mol Diagn. 2008;8:579-85 pubmed publisher
    Proliferating cells, in particular tumor cells, express a dimeric isoenzyme of pyruvate kinase, termed Tumor M2 pyruvate kinase...
  15. Ayi K, Liles W, Gros P, Kain K. Adenosine triphosphate depletion of erythrocytes simulates the phenotype associated with pyruvate kinase deficiency and confers protection against Plasmodium falciparum in vitro. J Infect Dis. 2009;200:1289-99 pubmed publisher
    Erythrocytes from individuals with pyruvate kinase deficiency (PKD) are resistant to invasion by Plasmodium falciparum parasites, and erythrocytes infected with ring-stage parasites are preferentially cleared by macrophages in vitro...
  16. Monge C, Beraud N, Tepp K, Pelloux S, Chahboun S, Kaambre T, et al. Comparative analysis of the bioenergetics of adult cardiomyocytes and nonbeating HL-1 cells: respiratory chain activities, glycolytic enzyme profiles, and metabolic fluxes. Can J Physiol Pharmacol. 2009;87:318-26 pubmed publisher
    ..On the contrary, the activities of glycolytic enzymes, hexokinase (HK), and pyruvate kinase (PK) were increased in HL-1 cells, and these cells effectively transformed glucose into lactate...
  17. Sepp M, Vendelin M, Vija H, Birkedal R. ADP compartmentation analysis reveals coupling between pyruvate kinase and ATPases in heart muscle. Biophys J. 2010;98:2785-93 pubmed publisher
    ..In addition, our experimental data show that considerable activity of endogenous pyruvate kinase (PK) remains in the cardiomyocytes after permeabilization...
  18. Spoden G, Rostek U, Lechner S, Mitterberger M, Mazurek S, Zwerschke W. Pyruvate kinase isoenzyme M2 is a glycolytic sensor differentially regulating cell proliferation, cell size and apoptotic cell death dependent on glucose supply. Exp Cell Res. 2009;315:2765-74 pubmed publisher
    The glycolytic key regulator pyruvate kinase M2 (M2-PK or PKM2) can switch between a highly active tetrameric and an inactive dimeric form. The transition between the two conformations regulates the glycolytic flux in tumor cells...
  19. Benesch C, Schneider C, Voelker H, Kapp M, Caffier H, Krockenberger M, et al. The clinicopathological and prognostic relevance of pyruvate kinase M2 and pAkt expression in breast cancer. Anticancer Res. 2010;30:1689-94 pubmed
    Cancer cell growth has been described to depend on glucose utilization. Activation of Akt and up-regulation of pyruvate kinase M2 (M2-PK) are attributes of tumour glycolysis...
  20. Bakszt R, Wernimont A, Allali Hassani A, Mok M, Hills T, Hui R, et al. The crystal structure of Toxoplasma gondii pyruvate kinase 1. PLoS ONE. 2010;5:e12736 pubmed publisher
    b>Pyruvate kinase (PK), which catalyzes the final step in glycolysis converting phosphoenolpyruvate to pyruvate, is a central metabolic regulator in most organisms...
  21. Mukherjee J, Phillips J, Zheng S, Wiencke J, Ronen S, Pieper R. Pyruvate kinase M2 expression, but not pyruvate kinase activity, is up-regulated in a grade-specific manner in human glioma. PLoS ONE. 2013;8:e57610 pubmed publisher
    Normal tissues express the M1 isoform of pyruvate kinase (PK) that helps generate and funnel pyruvate into the mitochondria for ATP production...
  22. Zoraghi R, See R, Gong H, Lian T, Swayze R, Finlay B, et al. Functional analysis, overexpression, and kinetic characterization of pyruvate kinase from methicillin-resistant Staphylococcus aureus. Biochemistry. 2010;49:7733-47 pubmed publisher
    ..Here we report the essentiality and kinetic properties of MRSA pyruvate kinase (PK). Targetron-mediated gene disruption demonstrated PK is essential for S...
  23. Abdel Fattah M, Abdel Ghany E, Adel A, Mosallam D, Kamal S. Glucose-6-phosphate dehydrogenase and red cell pyruvate kinase deficiency in neonatal jaundice cases in egypt. Pediatr Hematol Oncol. 2010;27:262-71 pubmed publisher
    ..Neonatal red cell pyruvate kinase (PK) deficiency may cause clinical patterns, ranging from extremely severe hemolytic anemia to moderate ..
  24. O CONNELL K, Doran P, Gannon J, Ohlendieck K. Lectin-based proteomic profiling of aged skeletal muscle: decreased pyruvate kinase isozyme M1 exhibits drastically increased levels of N-glycosylation. Eur J Cell Biol. 2008;87:793-805 pubmed publisher
    ..b>Pyruvate kinase isoform M1 with protein accession number gi|16757994|, exhibiting a pI of 6...
  25. Boxer M, Jiang J, Vander Heiden M, Shen M, Skoumbourdis A, Southall N, et al. Evaluation of substituted N,N'-diarylsulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase. J Med Chem. 2010;53:1048-55 pubmed publisher
    ..Pharmacological activators of a tumor cell specific pyruvate kinase isozyme (PKM2) may be an approach for altering the classic Warburg effect characteristic of aberrant ..
  26. Guzun R, Timohhina N, Tepp K, Monge C, Kaambre T, Sikk P, et al. Regulation of respiration controlled by mitochondrial creatine kinase in permeabilized cardiac cells in situ. Importance of system level properties. Biochim Biophys Acta. 2009;1787:1089-105 pubmed publisher
    ..analysis of the regulation of respiration by mitochondrial creatine kinase was performed in the presence of pyruvate kinase and phosphoenolpyruvate to simulate interaction of mitochondria with glycolytic enzymes...
  27. Lee J. Modulation of allostery of pyruvate kinase by shifting of an ensemble of microstates. Acta Biochim Biophys Sin (Shanghai). 2008;40:663-9 pubmed
    ..However, there are still a number of issues that remain unresolved. In this review we used mammalian pyruvate kinase (PK) as a model system to understand the role of protein dynamics in modulating cooperativity...
  28. Herman P, Lee J. Functional energetic landscape in the allosteric regulation of muscle pyruvate kinase. 2. Fluorescence study. Biochemistry. 2009;48:9456-65 pubmed publisher
    The energetic landscape of the allosteric regulatory mechanism of rabbit muscle pyruvate kinase (RMPK) was characterized by isothermal titration calorimetry (ITC). Four novel insights were uncovered. (1) ADP exhibits a dual property...
  29. Zhang Z, Liu Q, Che Y, Yuan X, Dai L, Zeng B, et al. Antigen presentation by dendritic cells in tumors is disrupted by altered metabolism that involves pyruvate kinase M2 and its interaction with SOCS3. Cancer Res. 2010;70:89-98 pubmed publisher
    ..Here, we show that intracellular SOCS3 in DCs binds to pyruvate kinase type M2 (M2-PK), which plays a critical role in ATP production through glycolysis...
  30. Ferguson E, Rathmell J. New roles for pyruvate kinase M2: working out the Warburg effect. Trends Biochem Sci. 2008;33:359-62 pubmed publisher
    ..Two recent studies demonstrate that an embryonic- and cancer-cell-specific isoform of the enzyme pyruvate kinase M2 (PKM2) is regulated by binding to phospho-tyrosine motifs and promotes increased cell growth and tumor ..
  31. Rider N, Strauss K, Brown K, Finkenstedt A, Puffenberger E, Hendrickson C, et al. Erythrocyte pyruvate kinase deficiency in an old-order Amish cohort: longitudinal risk and disease management. Am J Hematol. 2011;86:827-34 pubmed publisher
    b>Pyruvate kinase deficiency is a chronic illness with age specific consequences. Newborns suffer life-threatening hemolytic crisis and hyperbilirubinemia...
  32. Zhang Y, Xiao W, Luo L, Pang J, Rong W, He C. Downregulation of OsPK1, a cytosolic pyruvate kinase, by T-DNA insertion causes dwarfism and panicle enclosure in rice. Planta. 2012;235:25-38 pubmed publisher
    b>Pyruvate kinase (PK) catalyzes the final step of glycolysis. There are few reports on the role of PK in rice...
  33. Alves J, Machado P, Silva J, Gonçalves N, Ribeiro L, Faustino P, et al. Analysis of malaria associated genetic traits in Cabo Verde, a melting pot of European and sub Saharan settlers. Blood Cells Mol Dis. 2010;44:62-8 pubmed publisher
    ..We also included the analysis of the pyruvate kinase deficiency associated gene, reported as putatively associated with resistance to the disease...
  34. Anastasiou D, Poulogiannis G, Asara J, Boxer M, Jiang J, Shen M, et al. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science. 2011;334:1278-83 pubmed publisher
    ..cells, acute increases in intracellular concentrations of ROS caused inhibition of the glycolytic enzyme pyruvate kinase M2 (PKM2) through oxidation of Cys(358)...
  35. Johnson M, Maestranzi S, Duffy A, Dewar D, Ciclitira P, Sherwood R, et al. Faecal M2-pyruvate kinase: a novel, noninvasive marker of ileal pouch inflammation. Eur J Gastroenterol Hepatol. 2009;21:544-50 pubmed publisher
    Dimeric M2-pyruvate kinase (dM2-PK) is overexpressed in tumour cells with rapid cell turnover. Its concentrations correlate well with the staging and metastatic capability of the tumour cells...
  36. Varghese B, Swaminathan G, Plotnikov A, Tzimas C, Yang N, Rui H, et al. Prolactin inhibits activity of pyruvate kinase M2 to stimulate cell proliferation. Mol Endocrinol. 2010;24:2356-65 pubmed publisher
    ..PRL signaling is mediated through its receptor (PRLr). A proteomics screen identified the pyruvate kinase M2 (PKM2), a glycolytic enzyme known to play an important role in tumorigenesis, as a protein that ..
  37. Mazurek S. Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells. Int J Biochem Cell Biol. 2011;43:969-80 pubmed publisher
    ..In tumor cells, the glycolytic pyruvate kinase isoenzyme M2 (PKM2, M2-PK) determines whether glucose is converted to lactate for regeneration of energy (..
  38. Cortes Cros M, Hemmerlin C, Ferretti S, Zhang J, Gounarides J, Yin H, et al. M2 isoform of pyruvate kinase is dispensable for tumor maintenance and growth. Proc Natl Acad Sci U S A. 2013;110:489-94 pubmed publisher
    ..In addition, in tumors there is a predominance of expression of the M2 isoform of pyruvate kinase (PKM2)...
  39. Jiang M, Zhang Y, Liu M, Lan M, Fei J, Fan W, et al. Hypermethylation of hepatic glucokinase and L-type pyruvate kinase promoters in high-fat diet-induced obese rats. Endocrinology. 2011;152:1284-9 pubmed publisher
    ..we report that DNA hypermethylation is correlated with a decline in hepatic glucokinase (Gck) and L-type pyruvate kinase (LPK) expression in high-fat diet-induced obese rats as compared with the control diet group...
  40. Fenton A. Identification of allosteric-activating drug leads for human liver pyruvate kinase. Methods Mol Biol. 2012;796:369-82 pubmed publisher
    ..Activation of human liver pyruvate kinase (hL-PYK) in an effort to create a glycolytic/gluconeogenic futile cycle is one potential mechanism to ..
  41. Bluemlein K, Grüning N, Feichtinger R, Lehrach H, Kofler B, Ralser M. No evidence for a shift in pyruvate kinase PKM1 to PKM2 expression during tumorigenesis. Oncotarget. 2011;2:393-400 pubmed
    ..from a switch in the expression of alternative splice forms (PKM1 and PKM2) of the glycolytic enzyme pyruvate kinase (PK), which is also important for malignant transformation...
  42. Chan B, Ip M, Lau C, Lui S, Jolivalt C, Ganem Elbaz C, et al. Synergistic effects of baicalein with ciprofloxacin against NorA over-expressed methicillin-resistant Staphylococcus aureus (MRSA) and inhibition of MRSA pyruvate kinase. J Ethnopharmacol. 2011;137:767-73 pubmed publisher
    ..The effect of baicalein on inhibiting the enzymatic activity of a newly discovered MRSA-specific pyruvate kinase (PK), which is essential for Staphylococcus aureus growth and survival was also examined...
  43. Wei W, Li H, Chen C, Yang C, Lee S, Wang C, et al. SARS-CoV nucleocapsid protein interacts with cellular pyruvate kinase protein and inhibits its activity. Arch Virol. 2012;157:635-45 pubmed publisher
    ..b>Pyruvate kinase (liver) was found to interact with SARS-CoV nucleocapsid protein in this experiment...
  44. Iori E, Millioni R, Puricelli L, Arrigoni G, Lenzini L, Trevisan R, et al. Glycolytic enzyme expression and pyruvate kinase activity in cultured fibroblasts from type 1 diabetic patients with and without nephropathy. Biochim Biophys Acta. 2008;1782:627-33 pubmed publisher
    ..b>Pyruvate kinase (PK) activity was also determined. Human skin fibroblasts were grown in normal glucose (6 mM)...
  45. Maeda T, Saito T, Harb O, Roos D, Takeo S, Suzuki H, et al. Pyruvate kinase type-II isozyme in Plasmodium falciparum localizes to the apicoplast. Parasitol Int. 2009;58:101-5 pubmed publisher
    Bioinformatics research on Plasmodium falciparum revealed two isoforms of pyruvate kinase: type-I and type-II enzymes...
  46. Chen M, Zhang J, Manley J. Turning on a fuel switch of cancer: hnRNP proteins regulate alternative splicing of pyruvate kinase mRNA. Cancer Res. 2010;70:8977-80 pubmed publisher
    ..to aerobic glycolysis is partly achieved by a switch in the splice isoforms of the glycolytic enzyme pyruvate kinase. Although normal cells express the pyruvate kinase M1 isoform (PKM1), tumor cells predominantly express the ..
  47. Dhar D, Olde Damink S, Brindley J, Godfrey A, Chapman M, Sandanayake N, et al. Pyruvate kinase M2 is a novel diagnostic marker and predicts tumor progression in human biliary tract cancer. Cancer. 2013;119:575-85 pubmed publisher
    ..This study investigated whether the M2 isotype of pyruvate kinase (M2-PK), which serves as the key regulator of cellular energy metabolism in proliferating cells, could play a ..
  48. Turner D, Leach S, Mack D, Uusoue K, McLernon R, Hyams J, et al. Faecal calprotectin, lactoferrin, M2-pyruvate kinase and S100A12 in severe ulcerative colitis: a prospective multicentre comparison of predicting outcomes and monitoring response. Gut. 2010;59:1207-12 pubmed publisher
    ..baseline for all four markers (calprotectin 4215 microg/g (2297-8808); lactoferrin 212 microg/g (114-328); M2-pyruvate kinase (M2-PK) 363 U/g (119-3104); and S100A12 469 microg/g (193-1112))...
  49. Chavadi S, Wooff E, Coldham N, Sritharan M, Hewinson R, Gordon S, et al. Global effects of inactivation of the pyruvate kinase gene in the Mycobacterium tuberculosis complex. J Bacteriol. 2009;191:7545-53 pubmed publisher
    ..tuberculosis DeltapykA Deltaald double mutant showed little additional phenotypic effect. Overall, these data show that the loss of the pykA gene has powerful, global effects on proteins associated with central metabolism. ..
  50. Hitosugi T, Kang S, Vander Heiden M, Chung T, Elf S, Lythgoe K, et al. Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth. Sci Signal. 2009;2:ra73 pubmed publisher
    ..We found that oncogenic forms of fibroblast growth factor receptor type 1 inhibit the pyruvate kinase M2 (PKM2) isoform by direct phosphorylation of PKM2 tyrosine residue 105 (Y(105))...
  51. Nisman B, Yutkin V, Nechushtan H, Gofrit O, Peretz T, Gronowitz S, et al. Circulating tumor M2 pyruvate kinase and thymidine kinase 1 are potential predictors for disease recurrence in renal cell carcinoma after nephrectomy. Urology. 2010;76:513.e1-6 pubmed publisher
    b>Pyruvate kinase type M2 (TuM2-PK) and thymidine kinase 1 (TK1) are the key enzymes involved in tumor cells metabolism and proliferation...
  52. Bayley J, Devilee P. The Warburg effect in 2012. Curr Opin Oncol. 2012;24:62-7 pubmed publisher
    ..The M2 tumor-specific isoform of pyruvate kinase has generated much interest, but it has now been reported that PKM2 is not specific to tumors...
  53. Axerio Cilies P, See R, Zoraghi R, Worral L, Lian T, Stoynov N, et al. Cheminformatics-driven discovery of selective, nanomolar inhibitors for staphylococcal pyruvate kinase. ACS Chem Biol. 2012;7:350-9 pubmed publisher
    ..Here we report the discovery of inhibitors that are highly potent against one such hub target, staphylococcal pyruvate kinase (PK)...
  54. Meza E, Becker J, Bolivar F, Gosset G, Wittmann C. Consequences of phosphoenolpyruvate:sugar phosphotranferase system and pyruvate kinase isozymes inactivation in central carbon metabolism flux distribution in Escherichia coli. Microb Cell Fact. 2012;11:127 pubmed publisher
    ..W3110 derivative strains that lack the main PEP consumers PEP:sugar phosphotransferase system (PTS-) and pyruvate kinase isozymes PykA and PykF (PTS-pykA- and PTS-pykF-)...
  55. Zoraghi R, Worrall L, See R, Strangman W, Popplewell W, Gong H, et al. Methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase as a target for bis-indole alkaloids with antibacterial activities. J Biol Chem. 2011;286:44716-25 pubmed publisher
    ..We have recently identified pyruvate kinase (PK) as a potential novel drug target based upon it being an essential hub in the MRSA interactome (Cherkasov,..
  56. Feiden S, Wolfrum U, Wegener G, Kamp G. Expression and compartmentalisation of the glycolytic enzymes GAPDH and pyruvate kinase in boar spermatogenesis. Reprod Fertil Dev. 2008;20:713-23 pubmed
    Boar spermatozoa contain isoforms of both glyceraldehyde 3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12) and pyruvate kinase (PK, EC 2.7.1.40). The sperm-specific forms, GAPDH-S and PK-S, are tightly bound to cell structures...
  57. Chen J, Xie J, Jiang Z, Wang B, Wang Y, Hu X. Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2. Oncogene. 2011;30:4297-306 pubmed publisher
    ..Here, we showed that shikonin and its analogs are inhibitors of tumor-specific pyruvate kinase-M2 (PKM2), among which shikonin and its enantiomeric isomer alkannin were the most potent and showed ..
  58. Meza N, Alonso Ferrero M, Navarro S, Quintana Bustamante O, Valeri A, Garcia Gomez M, et al. Rescue of pyruvate kinase deficiency in mice by gene therapy using the human isoenzyme. Mol Ther. 2009;17:2000-9 pubmed publisher
    Human erythrocyte R-type pyruvate kinase deficiency (PKD) is a disorder caused by mutations in the PKLR gene that produces chronic nonspherocytic hemolytic anemia...
  59. Ryu H, Walker J, Kim S, Koo N, Barak L, Noguchi T, et al. Regulation of M2-type pyruvate kinase mediated by the high-affinity IgE receptors is required for mast cell degranulation. Br J Pharmacol. 2008;154:1035-46 pubmed publisher
    M2-type pyruvate kinase (M2PK) was found to interact directly with the 'ITAM' region of the gamma chain of the high-affinity IgE receptor (FcvarepsilonRI)...
  60. Herman P, Lee J. Functional energetic landscape in the allosteric regulation of muscle pyruvate kinase. 1. Calorimetric study. Biochemistry. 2009;48:9448-55 pubmed publisher
    Rabbit muscle pyruvate kinase (RMPK) is an important allosteric enzyme of the glycolytic pathway catalyzing a transfer of the phosphate from phosphoenolpyruvate (PEP) to ADP...
  61. Zoraghi R, See R, Axerio Cilies P, Kumar N, Gong H, Moreau A, et al. Identification of pyruvate kinase in methicillin-resistant Staphylococcus aureus as a novel antimicrobial drug target. Antimicrob Agents Chemother. 2011;55:2042-53 pubmed publisher
    ..Using the architecture of the MRSA interactome, we identified pyruvate kinase (PK) as a potential novel drug target based upon it being a highly connected, essential hub in the MRSA ..
  62. David C, Chen M, Assanah M, Canoll P, Manley J. HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature. 2010;463:364-8 pubmed publisher
    ..In mammals, this is partly achieved through control of pyruvate kinase isoform expression...
  63. Dimou M, Paunescu A, Aivalakis G, Flemetakis E, Katinakis P. Co-localization of carbonic anhydrase and phosphoenol-pyruvate carboxylase and localization of pyruvate kinase in roots and hypocotyls of etiolated Glycine max seedlings. Int J Mol Sci. 2009;10:2896-910 pubmed publisher
    ..GmPK3 expression, coding for a cytoplasmic isoform of pyruvate kinase, was detected in all different root cell types, suggesting that both phosphoenolpyruvate-utilizing enzymes ..
  64. Feng X, Cao L, Wang F, Zhang X, Lu S. [Inhibition of pyruvate kinase mRNA expression in Giardia lamblia by specific hammerhead ribozyme]. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2010;28:257-60 pubmed
    To inhibit the expression of pyruvate kinase (PK) mRNA in Giardia lamblia by specific hammerhead ribozyme.
  65. Iqbal M, Bamezai R. Resveratrol inhibits cancer cell metabolism by down regulating pyruvate kinase M2 via inhibition of mammalian target of rapamycin. PLoS ONE. 2012;7:e36764 pubmed publisher
    Metabolism of cancer cells with pyruvate kinase M2 (PKM2) at its centre stage has assumed a prime significance in cancer research in recent times...
  66. Zhou C, Li X, Sun H, Zhang B, Han Y, Jiang Y, et al. Pyruvate kinase type M2 is upregulated in colorectal cancer and promotes proliferation and migration of colon cancer cells. IUBMB Life. 2012;64:775-82 pubmed publisher
    b>Pyruvate kinase type M2 (PKM2) has been reported to be involved in aerobic glycolysis and cell growth in various tumors...
  67. Spoden G, Morandell D, Ehehalt D, Fiedler M, Jansen Durr P, Hermann M, et al. The SUMO-E3 ligase PIAS3 targets pyruvate kinase M2. J Cell Biochem. 2009;107:293-302 pubmed publisher
    b>Pyruvate kinase M2 (M2-PK) controls the rate-limiting step at the end of the glycolytic pathway in normal proliferating and tumor cells. Other functions of M2-PK in addition to its role in glycolysis are little understood...
  68. Tulloch L, Morgan H, Hannaert V, Michels P, Fothergill Gilmore L, Walkinshaw M. Sulphate removal induces a major conformational change in Leishmania mexicana pyruvate kinase in the crystalline state. J Mol Biol. 2008;383:615-26 pubmed publisher
    We report X-ray structures of pyruvate kinase from Leishmania mexicana (LmPYK) that are trapped in different conformations...
  69. Iqbal M, Siddiqui F, Chaman N, Gupta V, Kumar B, Gopinath P, et al. Missense mutations in pyruvate kinase M2 promote cancer metabolism, oxidative endurance, anchorage independence, and tumor growth in a dominant negative manner. J Biol Chem. 2014;289:8098-105 pubmed publisher
  70. Bettaieb A, Bakke J, Nagata N, Matsuo K, Xi Y, Liu S, et al. Protein tyrosine phosphatase 1B regulates pyruvate kinase M2 tyrosine phosphorylation. J Biol Chem. 2013;288:17360-71 pubmed publisher
    ..Here we identify pyruvate kinase M2 (PKM2) as a novel PTP1B substrate in adipocytes...
  71. Chen M, David C, Manley J. Concentration-dependent control of pyruvate kinase M mutually exclusive splicing by hnRNP proteins. Nat Struct Mol Biol. 2012;19:346-54 pubmed publisher
    Expression of the mammalian pyruvate kinase M (PKM) gene provides an important example of mutually exclusive splicing. We showed previously that the hnRNP proteins A1, A2 and PTB have a crucial role in this process...
  72. Chiavarina B, Whitaker Menezes D, Martinez Outschoorn U, Witkiewicz A, Birbe R, Howell A, et al. Pyruvate kinase expression (PKM1 and PKM2) in cancer-associated fibroblasts drives stromal nutrient production and tumor growth. Cancer Biol Ther. 2011;12:1101-13 pubmed publisher
    ..To this end, normal human fibroblasts were genetically-engineered to express the two isoforms of pyruvate kinase M (PKM1 and PKM2), a key enzyme in the glycolytic pathway...
  73. Lv L, Li D, Zhao D, Lin R, Chu Y, Zhang H, et al. Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth. Mol Cell. 2011;42:719-30 pubmed publisher
    ..Tumor cells commonly express the embryonic M2 isoform of pyruvate kinase (PKM2) that may contribute to the metabolism shift from oxidative phosphorylation to aerobic glycolysis and ..
  74. Aloysius M, Zaitoun A, Bates T, Albasri A, Ilyas M, Rowlands B, et al. Complete absence of M2-pyruvate kinase expression in benign pancreatic ductal epithelium and pancreaticobiliary and duodenal neoplasia. BMC Cancer. 2009;9:327 pubmed publisher
    Elevated serum concentrations of M2-pyruvate kinase (M2-PK) correlate with poor prognosis in patients with pancreaticobiliary and duodenal cancer, but the expression of M2-PK in formalin-fixed pancreatic tissue is unknown...
  75. Clower C, Chatterjee D, Wang Z, Cantley L, Vander Heiden M, Krainer A. The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism. Proc Natl Acad Sci U S A. 2010;107:1894-9 pubmed publisher
    ..This distinctive metabolism involves expression of the embryonic M2 isozyme of pyruvate kinase, in contrast to the M1 isozyme normally expressed in differentiated cells, and it confers a proliferative ..
  76. Day A, Judd T, Lemberg D, Leach S. Fecal M2-PK in children with Crohn's disease: a preliminary report. Dig Dis Sci. 2012;57:2166-70 pubmed publisher
    ..Stool markers of inflammation, such as M2-pyruvate kinase (M2-PK), permit more direct assessment of mucosal inflammation...
  77. Goldberg M, Sharp P. Pyruvate kinase M2-specific siRNA induces apoptosis and tumor regression. J Exp Med. 2012;209:217-24 pubmed publisher
    ..b>Pyruvate kinase (PK) exists in M1 (PKM1) and M2 (PKM2) isoforms...
  78. Jeffery J, Lewis S, Ayling R. Fecal dimeric M2-pyruvate kinase (tumor M2-PK) in the differential diagnosis of functional and organic bowel disorders. Inflamm Bowel Dis. 2009;15:1630-4 pubmed publisher
    ..More recently, the dimeric isoform of M2-pyruvate kinase (tumor M2-PK) has been suggested as a marker of gastrointestinal inflammation...
  79. Fenton A, Hutchinson M. The pH dependence of the allosteric response of human liver pyruvate kinase to fructose-1,6-bisphosphate, ATP, and alanine. Arch Biochem Biophys. 2009;484:16-23 pubmed publisher
    The allosteric regulation of human liver pyruvate kinase (hL-PYK) by fructose-1,6-bisphosphate (Fru-1,6-BP; activator), ATP (inhibitor) and alanine (Ala; inhibitor) was monitored over a pH range from 6.5 to 8.0 at 37 degrees C...
  80. Arora G, Sajid A, Gupta M, Bhaduri A, Kumar P, Basu Modak S, et al. Understanding the role of PknJ in Mycobacterium tuberculosis: biochemical characterization and identification of novel substrate pyruvate kinase A. PLoS ONE. 2010;5:e10772 pubmed publisher
    ..tuberculosis membrane-associated protein fraction is treated with the active kinase and glycolytic enzyme Pyruvate kinase A (mtPykA) is identified as one of the potential substrates of PknJ...
  81. Vander Heiden M, Christofk H, Schuman E, Subtelny A, Sharfi H, HARLOW E, et al. Identification of small molecule inhibitors of pyruvate kinase M2. Biochem Pharmacol. 2010;79:1118-24 pubmed publisher
    ..Cancer cells universally express the M2 isoform of the glycolytic enzyme pyruvate kinase (PKM2), and previous work has demonstrated that PKM2 expression is necessary for aerobic glycolysis and cell ..