Pklr

Summary

Gene Symbol: Pklr
Description: pyruvate kinase L/R
Alias: PK1, PKL, Pklg, pyruvate kinase PKLR, L-PK, pyruvate kinase isozymes L/R, pyruvate kinase isozymes R/L, pyruvate kinase, liver and RBC, pyruvate kinase, liver and red blood cell
Species: rat
Products:     Pklr

Top Publications

  1. Wang H, Chu W, Das S, Ren Q, Hasstedt S, Elbein S. Liver pyruvate kinase polymorphisms are associated with type 2 diabetes in northern European Caucasians. Diabetes. 2002;51:2861-5 pubmed
    ..cell, liver, pancreatic beta-cells, small intestine, and proximal renal tubule are encoded by the 12 exons of the PKLR gene, which maps to chromosome 1q23...
  2. Becker W, Kluge R, Kantner T, Linnartz K, Korn M, Tschank G, et al. Differential hepatic gene expression in a polygenic mouse model with insulin resistance and hyperglycemia: evidence for a combined transcriptional dysregulation of gluconeogenesis and fatty acid synthesis. J Mol Endocrinol. 2004;32:195-208 pubmed
  3. Barbera A, Gomis R, Prats N, Rodriguez Gil J, Domingo M, Gomis R, et al. Tungstate is an effective antidiabetic agent in streptozotocin-induced diabetic rats: a long-term study. Diabetologia. 2001;44:507-13 pubmed
    ..In this study, we examined the effectiveness of long-term tungstate treatment of streptozotocin-induced-diabetic rats...
  4. Krones A, Jungermann K, Kietzmann T. Cross-talk between the signals hypoxia and glucose at the glucose response element of the L-type pyruvate kinase gene. Endocrinology. 2001;142:2707-18 pubmed
    ..Our findings implicate that the cross-talk between oxygen and glucose might have a fundamental role in the regulation of several physiological and pathophysiological processes. ..
  5. Sakai H, Ohta T. Molecular cloning and nucleotide sequence of the gene for pyruvate kinase of Bacillus stearothermophilus and the production of the enzyme in Escherichia coli. Evidence that the genes for phosphofructokinase and pyruvate kinase constitute an operon. Eur J Biochem. 1993;211:851-9 pubmed
    ..The homology of the sequence showed that the gene encodes phosphofructokinase. Both phosphofructokinase and pyruvate kinase were expressed in E. coli cells, and the evidence suggesting that both genes constitute an operon is presented. ..
  6. Faustova I, Loog M, Järv J. Probing L-pyruvate kinase regulatory phosphorylation site by mutagenesis. Protein J. 2012;31:592-7 pubmed publisher
  7. White R, McNulty S, Roman S, Garg U, Wirtz E, Kohlbrecher D, et al. Chromosomal localization, hematologic characterization, and iron metabolism of the hereditary erythroblastic anemia (hea) mutant mouse. Blood. 2004;104:1511-8 pubmed
    ..When this diet is removed there is reversion to anemia with concomitant loss of overloaded iron stores. We speculate that the hea/fsn gene is required for iron uptake into erythropoietic cells and for kidney iron reabsorption. ..
  8. Sánchez Gutiérrez J, Sánchez Arias J, Samper B, Feliu J. Modulation of gluconeogenesis by epinephrine in hepatocytes isolated from genetically obese (fa/fa) Zucker rats. Arch Biochem Biophys. 2000;373:249-54 pubmed
    ..This occurs in spite of an apparent decreased sensitivity of the adenylate cyclase system to the stimulatory effect of epinephrine in obese rat liver cells. ..
  9. Satoh S, Noaki T, Ishigure T, Osada S, Imagawa M, Miura N, et al. Nuclear factor 1 family members interact with hepatocyte nuclear factor 1alpha to synergistically activate L-type pyruvate kinase gene transcription. J Biol Chem. 2005;280:39827-34 pubmed
    ..Thus, we conclude that cooperative interaction between NF1 family members and HNF1alpha plays an important role in hepatic L-PK transcription. ..

More Information

Publications56

  1. Rosa T, de Souza Wyse A, Wajner M, Wannmacher C. Cysteamine prevents and reverses the inhibition of pyruvate kinase activity caused by cystine in rat heart. Biochim Biophys Acta. 2004;1689:114-9 pubmed
    ..Considering that cysteamine is used in patients with cystinosis because it causes parenchymal organ cystine depletion, the present data provide a possible new effect for this drug. ..
  2. Burke S, Collier J, Scott D. cAMP opposes the glucose-mediated induction of the L-PK gene by preventing the recruitment of a complex containing ChREBP, HNF4alpha, and CBP. FASEB J. 2009;23:2855-65 pubmed publisher
    ..We conclude that cAMP and glucose signaling converge on a complex containing ChREBP, HNF4alpha, and CBP, and that cAMP acts by disrupting this transcriptional complex assembled by glucose-derived signals. ..
  3. Kelley G, Ondrako J, Reks S. Fuel and hormone regulation of phospholipase C beta 1 and delta 1 overexpressed in RINm5F pancreatic beta cells. Mol Cell Endocrinol. 2001;177:107-15 pubmed
  4. Min oo G, Fortin A, Tam M, Nantel A, Stevenson M, Gros P. Pyruvate kinase deficiency in mice protects against malaria. Nat Genet. 2003;35:357-62 pubmed
    ..loss-of-function mutation (269T-->A, resulting in the amino acid substitution I90N) in the pyruvate kinase gene (Pklr) that underlies the malaria resistance in AcB55 and AcB61...
  5. Laes J, Ravoet M, Quan X, Van Vooren P, Szpirer J, Szpirer C. Improved radiation hybrid map of rat chromosome 2: colocalization of the genes encoding corticotropin-releasing hormone and IL6-receptor with quantitative trait loci regulating the inflammatory response. Cytogenet Cell Genet. 2001;92:130-3 pubmed
    ..Our data show that they reside within regions that were genetically defined as QTLs controlling the inflammatory response. These genes are thus both functional and positional candidates. ..
  6. Cuif M, Doiron B, Kahn A. Insulin and cyclic AMP act at different levels on transcription of the L-type pyruvate kinase gene. FEBS Lett. 1997;417:81-4 pubmed
    ..We propose that both insulin and cAMP act on expression of the L-PK gene at, at least, two levels: positive and negative regulation of glucokinase gene expression, and more downstream levels. ..
  7. Riu E, Ferre T, Hidalgo A, Mas A, Franckhauser S, Otaegui P, et al. Overexpression of c-myc in the liver prevents obesity and insulin resistance. FASEB J. 2003;17:1715-7 pubmed
    ..These results suggest that c-myc overexpression counteracted the obesity and insulin resistance induced by a high-fat diet by modulating the expression of genes that regulate hepatic metabolism. ..
  8. Canu G, De Bonis M, Minucci A, Capoluongo E. Red blood cell PK deficiency: An update of PK-LR gene mutation database. Blood Cells Mol Dis. 2016;57:100-9 pubmed publisher
    ..lumc.nl/LOVD2/mendelian_genes/home.php?select_db=PKLR) and Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/gene...
  9. Dhar Chowdhury P, Harrell M, Han S, Jankowska D, Parachuru L, Morrissey A, et al. The glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase, triose-phosphate isomerase, and pyruvate kinase are components of the K(ATP) channel macromolecular complex and regulate its function. J Biol Chem. 2005;280:38464-70 pubmed
    ..Our data are consistent with the concept that the activity of these enzymes (possibly by ATP formation in the immediate intracellular microenvironment of this macromolecular K(ATP) channel complex) causes channel closure. ..
  10. Collier J, Doan T, Daniels M, Schurr J, Kolls J, Scott D. c-Myc is required for the glucose-mediated induction of metabolic enzyme genes. J Biol Chem. 2003;278:6588-95 pubmed
    ..We conclude that multiple mechanisms exist to communicate the glucose-derived signal and that c-Myc has a key role in the hepatic glucose signaling pathway. ..
  11. Kanno H, Fujii H, Hirono A, Omine M, Miwa S. Identical point mutations of the R-type pyruvate kinase (PK) cDNA found in unrelated PK variants associated with hereditary hemolytic anemia. Blood. 1992;79:1347-50 pubmed
    ..These results indicate that the multiplicity of the mutant PK allele is smaller than expected, and that the silent mutation is a polymorphic change commonly distributed in the Japanese population. ..
  12. Pissard S, Max Audit I, Skopinski L, Vasson A, Vivien P, Bimet C, et al. Pyruvate kinase deficiency in France: a 3-year study reveals 27 new mutations. Br J Haematol. 2006;133:683-9 pubmed
    ..These results support the characterisation of PK mutations, and show that prenatal diagnosis can identify affected infants and prepare safer conditions for the birth. ..
  13. Boin I, Silva O, Souza M, Santos A, Leonardi L. Pyruvate kinase activation and lipoperoxidation after selective hepatic ischemia in Wistar rats. Acta Cir Bras. 2006;21 Suppl 1:19-23 pubmed
    ..The animals of group A showed reperfusion syndrome with a fall in MAP, activation of glycid metabolism through the glycolitic pathway and presence of lipid peroxidation compared to group B. ..
  14. Kanno H, Ballas S, Miwa S, Fujii H, Bowman H. Molecular abnormality of erythrocyte pyruvate kinase deficiency in the Amish. Blood. 1994;83:2311-6 pubmed
    ..Ouabain-insensitive K+ efflux was increased to 142% to 145% of normal controls and not inhibited by furosemide, as previously observed in HbSC disease RBCs. ..
  15. Burke S, Collier J, Scott D. cAMP prevents glucose-mediated modifications of histone H3 and recruitment of the RNA polymerase II holoenzyme to the L-PK gene promoter. J Mol Biol. 2009;392:578-88 pubmed publisher
    ..We conclude that the effects of glucose and cAMP are mediated in part by epigenetic modulation of histones. ..
  16. Zhaofan X, Jianguang T, Guangyi W, Hongtai T, Shengde G, Horton J. Effect of thermal injury on relative anaplerosis and gluconeogenesis in the rat during infusion of [U-13C] propionate. Burns. 2002;28:625-30 pubmed
    ..Similarly, flux through pyruvate kinase (again relative to citrate synthase) was significantly increased in burn injury. ..
  17. Lone Y, Simon M, Kahn A, Marie J. Sequences complementary to the brain-specific "identifier" sequences exist in L-type pyruvate kinase mRNA (a liver-specific messenger) and in transcripts especially abundant in muscle. J Biol Chem. 1986;261:1499-502 pubmed
    ..J., Bloom, F. E., Lai, C., Lerner, R. A., and Sutcliffe, J. G. (1984) Proc. Natl. Acad. Sci. U. S. A. 81, 713-717; Sutcliffe, J. G., Milner, R. J., Gottesfeld, J. M., and Reynolds, W. (1984) Science 225, 1308-1314). ..
  18. Mohammad S, Taha A, Akhtar K, Bamezai R, Baquer N. In vivo effect of Trigonella foenum graecum on the expression of pyruvate kinase, phosphoenolpyruvate carboxykinase, and distribution of glucose transporter (GLUT4) in alloxan-diabetic rats. Can J Physiol Pharmacol. 2006;84:647-54 pubmed
    ..Trigonella treatment partially restored the altered expression of PK and PEPCK. TSP treatment also corrected the alterations in the distribution of GLUT4 in the skeletal muscle...
  19. Brand I, Heinickel A. Key enzymes of carbohydrate metabolism as targets of the 11.5-kDa Zn(2+)-binding protein (parathymosin). J Biol Chem. 1991;266:20984-9 pubmed
    ..The behavior of glucose-6-phosphate dehydrogenase and glycerol-3-phosphate dehydrogenase from this tissue could not be followed. A possible function of ZnBP in supramolecular organization of carbohydrate metabolism is proposed. ..
  20. Hotta K, Kuwajima M, Ono A, Nakajima H, Shingu R, Miyagawa J, et al. Disordered expression of hepatic glycolytic and gluconeogenic enzymes in Otsuka Long-Evans Tokushima fatty rats with spontanteous long-term hyperglycemia. Biochim Biophys Acta. 1996;1289:145-9 pubmed
    ..These results suggest that the expression of glucose-6-phosphatase and fructose-1,6-biphosphatase is disordered in OLETF rats. ..
  21. Kanno H, Morimoto M, Fujii H, Tsujimura T, Asai H, Noguchi T, et al. Primary structure of murine red blood cell-type pyruvate kinase (PK) and molecular characterization of PK deficiency identified in the CBA strain. Blood. 1995;86:3205-10 pubmed
  22. Lone Y, Simon M, Kahn A, Marie J. Complete nucleotide and deduced amino acid sequences of rat L-type pyruvate kinase. FEBS Lett. 1986;195:97-100 pubmed
    ..The unusually long 3'-untranslated extension contains a repetitive element complementary to the 'brain-specific' identifier sequence described by Sutcliffe et al. [(1982) Proc. Natl. Acad. Sci. USA 79, 4942-4946]. ..
  23. 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
  24. Rodriguez Gil J, Fernández Novell J, Barbera A, Guinovart J. Lithium's effects on rat liver glucose metabolism in vivo. Arch Biochem Biophys. 2000;375:377-84 pubmed
  25. Collier J, Zhang P, Pedersen K, Burke S, Haycock J, Scott D. c-Myc and ChREBP regulate glucose-mediated expression of the L-type pyruvate kinase gene in INS-1-derived 832/13 cells. Am J Physiol Endocrinol Metab. 2007;293:E48-56 pubmed
  26. Ichai C, El Mir M, Nogueira V, Piquet M, Chauvin C, Fontaine E, et al. Exogenous Mg-ATP induces a large inhibition of pyruvate kinase in intact rat hepatocytes. J Biol Chem. 2001;276:6398-403 pubmed
    ..This newly described short-term regulation of pyruvate kinase occurs only in the intact cell and may open new potentials for the pharmacological regulation of pyruvate kinase in vivo. ..
  27. Wimhurst J, Manchester K. Induction and suppression of the key enzymes of glycolysis and gluconeogenesis in isolated perfused rat liver in response to glucose, fructose and lactate. Biochem J. 1973;134:143-56 pubmed
    ..Lipid was found to increase only in the experiments with high fructose concentrations. 7. Perfusion with either fructose or glucose decreased the rates of ureogenesis; addition of cycloheximide increased urea efflux from the liver. ..
  28. Marie J, Simon M, Lone Y, Cognet M, Kahn A. Tissue-specific heterogeneity of the 3'-untranslated region of L-type pyruvate kinase mRNAs. Eur J Biochem. 1986;158:33-41 pubmed
    ..The role of an 'identifier sequence' located in the 3' noncoding sequence of the 3.2-kb species in such a tissue-specific use of alternative polyadenylation sites is discussed. ..
  29. Lan M, Wang H, Chong J, Breslin M. Coupling of glucose response element from L-type pyruvate kinase and G6Pase promoter enhances glucose responsive activity in hepatoma cells. Mol Cell Biochem. 2007;300:191-6 pubmed
    ..The construction of a chimeric promoter with stronger and more sensitive responsive activity to glucose and insulin in liver cells could further advance studies in insulin gene therapy. ..
  30. Eckert D, Zhang P, Collier J, O Doherty R, Scott D. Detailed molecular analysis of the induction of the L-PK gene by glucose. Biochem Biophys Res Commun. 2008;372:131-6 pubmed publisher
    ..The results of these studies demonstrate fundamental details of the molecular mechanism of glucose activated gene expression. ..
  31. Kanno H, Wei D, Chan L, Mizoguchi H, Ando M, Nakahata T, et al. Hereditary hemolytic anemia caused by diverse point mutations of pyruvate kinase gene found in Japan and Hong Kong. Blood. 1994;84:3505-9 pubmed
    ..Both the R- and M2-type PK were shown by polyacrylamide gel electrophoresis of the PK Hong Kong erythrocyte lysate, and this is the first report of a homozygous individual whose erythrocytes contain the immature (M2)-type isozyme. ..
  32. Valentini G, Chiarelli L, Fortin R, Dolzan M, Galizzi A, Abraham D, et al. Structure and function of human erythrocyte pyruvate kinase. Molecular basis of nonspherocytic hemolytic anemia. J Biol Chem. 2002;277:23807-14 pubmed
    ..Characterization of mutant proteins may serve as a valuable tool to assist with diagnosis and genetic counseling. ..
  33. Noguchi T, Yamada K, Inoue H, Matsuda T, Tanaka T. The L- and R-type isozymes of rat pyruvate kinase are produced from a single gene by use of different promoters. J Biol Chem. 1987;262:14366-71 pubmed
    ..Instead, the 5'-flanking region of exon R contained another promoter sequence of the CAT box. Thus, we conclude that the L- and R-type isozymes of pyruvate kinase are produced from a single gene by use of different promoters. ..
  34. Dombrauckas J, Santarsiero B, Mesecar A. Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis. Biochemistry. 2005;44:9417-29 pubmed
  35. Xu J, Christian B, Jump D. Regulation of rat hepatic L-pyruvate kinase promoter composition and activity by glucose, n-3 polyunsaturated fatty acids, and peroxisome proliferator-activated receptor-alpha agonist. J Biol Chem. 2006;281:18351-62 pubmed
    ..In conclusion, n-3 PUFA and WY14643/PPARalpha target different transcription factors to control L-PK gene transcription. MLX, the heterodimer partner for ChREBP, has emerged as a novel target for n-3 PUFA regulation. ..
  36. Machado P, Pereira R, Rocha A, Manco L, Fernandes N, Miranda J, et al. Malaria: looking for selection signatures in the human PKLR gene region. Br J Haematol. 2010;149:775-84 pubmed publisher
    ..of Short Tandem Repeats (STRs) and Single Nucleotide Polymorphisms (SNPs) in the pyruvate kinase-encoding gene (PKLR) and adjacent regions (chromosome 1q21) to look for malaria selective signatures in two sub-Saharan African ..
  37. Gunn J, Taylor C. Relationships between concentration of hepatic intermediary metabolites and induction of the key glycolytic enzymes in vivo. Biochem J. 1973;136:455-65 pubmed
    ..LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1973), 131, 5. ..
  38. Sirato Yasumoto S, Katsuta M, Okuyama Y, Takahashi Y, Ide T. Effect of sesame seeds rich in sesamin and sesamolin on fatty acid oxidation in rat liver. J Agric Food Chem. 2001;49:2647-51 pubmed
    ..Therefore, consumption of sesame rich in lignans results in physiological activity to alter lipid metabolism in a potentially beneficial manner. ..
  39. 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...
  40. Peters J, Nash H, Eicher E, Bulfield G. Polymorphism of kidney pyruvate kinase in the mouse is determined by a gene, Pk-3, on chromosome 9. Biochem Genet. 1981;19:757-69 pubmed
    ..In addition, our results indicate that the muscle (M1) and kidney (M2) pyruvate kinase isozymes share at least one genetic determinant and may in fact be determined by the same structural gene. ..
  41. Inoue H, Noguchi T, Tanaka T. Complete amino acid sequence of rat L-type pyruvate kinase deduced from the cDNA sequence. Eur J Biochem. 1986;154:465-9 pubmed
  42. Huong D, Ide T. Dietary lipoic acid-dependent changes in the activity and mRNA levels of hepatic lipogenic enzymes in rats. Br J Nutr. 2008;100:79-87 pubmed
    ..Lipoic acid appeared to reduce hepatic lipogenesis and hence decreases serum and liver lipid levels. Alterations in serum concentrations of insulin and (or) adiponectin may trigger this consequence. ..
  43. Jimenez de Asua L, Rozengurt E, Carminatti H. Some kinetic properties of liver pyruvate kinase (type L). 3. Effect of monovalent cations on its allosteric behavior. J Biol Chem. 1970;245:3901-5 pubmed
  44. Rockah R, Narinsky R, Frydman M, Cohen I, Zaizov R, Weizman A, et al. Linkage disequilibrium of common Gaucher disease mutations with a polymorphic site in the pyruvate kinase (PKLR) gene. Am J Med Genet. 1998;78:233-6 pubmed
    ..mutations in the GBA gene with different alleles of a highly polymorphic site in the adjacent pyruvate kinase (PKLR) gene...
  45. Manco L, Ribeiro M, Máximo V, Almeida H, Costa A, Freitas O, et al. A new PKLR gene mutation in the R-type promoter region affects the gene transcription causing pyruvate kinase deficiency. Br J Haematol. 2000;110:993-7 pubmed
    Mutations in the PKLR gene responsible for pyruvate kinase (PK)-deficient anaemia are mainly located in the coding regions: 11 are in the splicing sites and, recently, three mutations have been described in the promoter region...
  46. Andreasen C, Mogensen M, Borch Johnsen K, Sandbaek A, Lauritzen T, Almind K, et al. Lack of association between PKLR rs3020781 and NOS1AP rs7538490 and type 2 diabetes, overweight, obesity and related metabolic phenotypes in a Danish large-scale study: case-control studies and analyses of quantitative traits. BMC Med Genet. 2008;9:118 pubmed publisher
    Several studies in multiple ethnicities have reported linkage to type 2 diabetes on chromosome 1q21-25. Both PKLR encoding the liver pyruvate kinase and NOS1AP encoding the nitric oxide synthase 1 (neuronal) adaptor protein (CAPON) are ..
  47. Cognet M, Lone Y, Vaulont S, Kahn A, Marie J. Structure of the rat L-type pyruvate kinase gene. J Mol Biol. 1987;196:11-25 pubmed
    ..With both templates the start site of transcription appeared to be microheterogeneous, 19 to 14 bp before the ATG translation initiation codon. ..