phosphofructokinase 1

Summary

Summary: An allosteric enzyme that regulates glycolysis by catalyzing the transfer of a phosphate group from ATP to fructose-6-phosphate to yield fructose-1,6-bisphosphate. D-tagatose- 6-phosphate and sedoheptulose-7-phosphate also are acceptors. UTP, CTP, and ITP also are donors. In human phosphofructokinase-1, three types of subunits have been identified. They are PHOSPHOFRUCTOKINASE-1, MUSCLE TYPE; PHOSPHOFRUCTOKINASE-1, LIVER TYPE; and PHOSPHOFRUCTOKINASE-1, TYPE C; found in platelets, brain, and other tissues.

Top Publications

  1. Garfinkel L, Garfinkel D. Magnesium regulation of the glycolytic pathway and the enzymes involved. Magnesium. 1985;4:60-72 pubmed
    ..It is necessary to properly control the composition of assay mixtures (particularly with regard to metal ions) in order to determine what actually regulates the activity of an enzyme. ..
  2. Thomas S, Fell D. A control analysis exploration of the role of ATP utilisation in glycolytic-flux control and glycolytic-metabolite-concentration regulation. Eur J Biochem. 1998;258:956-67 pubmed
  3. Ronquist G, Rudolphi O, Engstrom I, Waldenstrom A. Familial phosphofructokinase deficiency is associated with a disturbed calcium homeostasis in erythrocytes. J Intern Med. 2001;249:85-95 pubmed
    ..Erythrocytes contain a 50 : 50 hybrid of M and L type. The deficiency of the muscle isoenzyme displays a symptomatology which is mainly characterized by myopathy, and a compensated haemolytic anaemia...
  4. Edelmann A, Kirchberger J, Heinisch J, Kopperschläger G. C-terminal modification of 6-phosphofructo-1-kinase from Saccharomyces cerevisiae and its influence on enzyme structure and activity. Biochem Biophys Res Commun. 2002;295:992-9 pubmed
    ..On the basis of our results we assume that the C-termini are important for the three-dimensional structure of the subunits determining their susceptibility to proteolysis and the ability to assembly to an active, oligomeric Pfk-1. ..
  5. Legisa M, Bencina M. Evidence for the activation of 6-phosphofructo-1-kinase by cAMP-dependent protein kinase in Aspergillus niger. FEMS Microbiol Lett. 1994;118:327-33 pubmed
    ..Additional evidence for covalent phosphorylation of inactive 6-phosphofructo-1-kinase was obtained by incubating both enzymes together with labelled [gamma-32P]ATP. The activating enzyme was partially purified from A. niger mycelium. ..
  6. Marin Hernandez A, Rodriguez Enriquez S, Vital González P, Flores Rodríguez F, Macias Silva M, Sosa Garrocho M, et al. Determining and understanding the control of glycolysis in fast-growth tumor cells. Flux control by an over-expressed but strongly product-inhibited hexokinase. FEBS J. 2006;273:1975-88 pubmed
    ..Therefore, the enhanced glycolytic flux in fast-growth tumor cells was still controlled by an over-produced, but Glc6P-inhibited hexokinase. ..
  7. Heinisch J. Isolation and characterization of the two structural genes coding for phosphofructokinase in yeast. Mol Gen Genet. 1986;202:75-82 pubmed
    ..This was not accompanied by an increased ethanol production. The sequences encoding the two subunits were shown to share homology. ..
  8. Vora S, Seaman C, Durham S, Piomelli S. Isozymes of human phosphofructokinase: identification and subunit structural characterization of a new system. Proc Natl Acad Sci U S A. 1980;77:62-6 pubmed
    ..The structural heterogeneity of erythrocyte PFK provides a molecular genetic basis for the differential organ involvement observed in some inherited PFK deficiency states in which myopathy or hemolysis or both can occur. ..
  9. Emmerling M, Bailey J, Sauer U. Glucose catabolism of Escherichia coli strains with increased activity and altered regulation of key glycolytic enzymes. Metab Eng. 1999;1:117-27 pubmed
    ..The flux data demonstrate that overexpression of even single enzymes early in a central pathway can increase the fluxes to a particular metabolic product, although it may not affect the glucose uptake rate. ..

More Information

Publications62

  1. Ruijter G, Panneman H, Visser J. Overexpression of phosphofructokinase and pyruvate kinase in citric acid-producing Aspergillus niger. Biochim Biophys Acta. 1997;1334:317-26 pubmed
    ..Thus, the fungus seems to adapt to overexpression of phosphofructokinase by decreasing the specific activity of the enzyme through a reduction in the level of fructose 2,6-bisphosphate. ..
  2. Vorgerd M, Karitzky J, Ristow M, Van Schaftingen E, Tegenthoff M, Jerusalem F, et al. Muscle phosphofructokinase deficiency in two generations. J Neurol Sci. 1996;141:95-9 pubmed
    ..This is the first description of proven muscle PFK deficiency (glycogenosis type VII) in two subsequent generations...
  3. Raben N, Sherman J. Mutations in muscle phosphofructokinase gene. Hum Mutat. 1995;6:1-6 pubmed
    ..Molecular diagnosis is now feasible for Ashkenazi patients who share two common mutations in the gene; the more frequent is an exon 5 splicing defect, which accounts for approximately 68% of mutant alleles in this population...
  4. Kemp R, Gunasekera D. Evolution of the allosteric ligand sites of mammalian phosphofructo-1-kinase. Biochemistry. 2002;41:9426-30 pubmed
    ..The two sites for activators, fructose 2,6-bisphosphate and AMP or ADP, have evolved from the catalytic site of the ancestral precursor. ..
  5. Daldal F. Molecular cloning of the gene for phosphofructokinase-2 of Escherichia coli and the nature of a mutation, pfkB1, causing a high level of the enzyme. J Mol Biol. 1983;168:285-305 pubmed
    ..The DNA sequence of the 408 base-pair fragments from pfkB+ and pfkB1 were found to differ only in a single residue, the pfkB1 mutation thus proving to be a C to T change at position about -12 from the initiation of transcription. ..
  6. Vora S, Davidson M, Seaman C, Miranda A, Noble N, Tanaka K, et al. Heterogeneity of the molecular lesions in inherited phosphofructokinase deficiency. J Clin Invest. 1983;72:1995-2006 pubmed
    ..Of the two, the M subunit appears to be more critical for adequate glycolytic flux in the erythrocyte, since its absence is correlated with hemolysis...
  7. Amit R, Bashan N, Abarbanel J, Shapira Y, Sofer S, Moses S. Fatal familial infantile glycogen storage disease: multisystem phosphofructokinase deficiency. Muscle Nerve. 1992;15:455-8 pubmed
    ..The possibility that this multisystem PFK-1 deficiency may be related to the absence of a yet unknown activator, common to all PFK-1 isozymes, is discussed...
  8. Castaño J, Nieto A, Feliu J. Inactivation of phosphofructokinase by glucagon in rat hepatocytes. J Biol Chem. 1979;254:5576-9 pubmed
    ..The inactivation of phosphofructokinase by nonsaturating concentration of glucagon is reversed spontaneously within 40 min of incubation and this reversion is accelerated by insulin. ..
  9. Tornheim K. Activation of muscle phosphofructokinase by fructose 2,6-bisphosphate and fructose 1,6-bisphosphate is differently affected by other regulatory metabolites. J Biol Chem. 1985;260:7985-9 pubmed
    ..These results are consistent with competition of the two fructose bisphosphates for the same binding site, but indicate that the conformational changes produced by their binding are different. ..
  10. Nendza R, Digweed M, Meyer H, Erdmann V, Mayr G. 5S-rRNA-containing ribonucleoproteins from rabbit muscle and liver. Complex and partial primary structures. Eur J Biochem. 1987;169:85-95 pubmed
    ..For the sarcoplasmic L5-5S-RNA complex a hitherto unknown interaction with phosphofructokinase-1, affecting the enzymatic properties, was demonstrated. ..
  11. Yamasaki T, Nakajima H, Kono N, Hotta K, Yamada K, Imai E, et al. Structure of the entire human muscle phosphofructokinase-encoding gene: a two-promoter system. Gene. 1991;104:277-82 pubmed
    ..These results indicated that the hPFK-M gene contains at least two promoter regions, facilitating the expression of the heterogeneous gene transcripts in a cell-type-specific manner. ..
  12. Vora S, Oskam R, Staal G. Isoenzymes of phosphofructokinase in the rat. Demonstration of the three non-identical subunits by biochemical, immunochemical and kinetic studies. Biochem J. 1985;229:333-41 pubmed
  13. Han B, Liu H, Hu X, Cai Y, Zheng D, Yuan Z. Molecular characterization of a glucokinase with broad hexose specificity from Bacillus sphaericus strain C3-41. Appl Environ Microbiol. 2007;73:3581-6 pubmed
    ..Our findings provide additional data that further elucidate the specific metabolic pathway and could be used for genetic improvement of B. sphaericus. ..
  14. Hotta K, Nakajima H, Yamasaki T, Hamaguchi T, Kuwajima M, Noguchi T, et al. Rat-liver-type phosphofructokinase mRNA. Structure, tissue distribution and regulation. Eur J Biochem. 1991;202:293-8 pubmed
    ..These results suggested that rat liver-type phosphofructokinase mRNA in the liver was not under control of diet or insulin, in contrast to glucokinase and L-type pyruvate kinase. ..
  15. 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. ..
  16. Ding Y, Ronimus R, Morgan H. Thermotoga maritima phosphofructokinases: expression and characterization of two unique enzymes. J Bacteriol. 2001;183:791-4 pubmed
    ..g., phosphoenolpyruvate) but was strongly inhibited by PP(i) and polyphosphate. The results suggest that the control of the Embden-Meyerhof pathway in this organism is likely to be modulated by pyrophosphate and/or polyphosphate. ..
  17. Byington C, Dunbrack R, Whitby F, Cohen F, Agabian N. Entamoeba histolytica: computer-assisted modeling of phosphofructokinase for the prediction of broad-spectrum antiparasitic agents. Exp Parasitol. 1997;87:194-202 pubmed
    ..histolytica and inhibited the growth of amebae in vitro. This class of compounds may have broad-spectrum antiparasitic activity and, in the future, may facilitate the treatment of serious parasitic infections. ..
  18. Alves A, Euverink G, Bibb M, Dijkhuizen L. Identification of ATP-dependent phosphofructokinase as a regulatory step in the glycolytic pathway of the actinomycete Streptomyces coelicolor A3(2). Appl Environ Microbiol. 1997;63:956-61 pubmed
    ..Further structural and functional analysis of the two actinomycete PFK enzymes should elucidate the features of these proteins that determine substrate specificity (ATP versus PPi) and allosteric (in)sensitivity. ..
  19. Tseung C, Carmona A. Comparative study of phosphofructokinase from rat small intestine and liver. Control by fructose-2,6-bisphosphate and other effectors. Acta Cient Venez. 1990;41:311-6 pubmed
    ..3 mM. These studies suggest that, under physiological conditions, the intestinal isoenzyme is more active than its liver counterpart. This may account for the high rate of aerobic glycolysis observed in the intestinal mucosa. ..
  20. Koster J, Slee R, van Berkel T. Isoenzymes of human phosphofructokinase. Clin Chim Acta. 1980;103:169-73 pubmed
    ..Leucocytes, erythrocytes and kidney also possess the liver (L-) type subunit and a small amount of L-type is present in brain. There is no L-type of phosphofructokinase present in muscle and heart tissue...
  21. Riley Lovingshimer M, Reinhart G. Equilibrium binding studies of a tryptophan-shifted mutant of phosphofructokinase from Bacillus stearothermophilus. Biochemistry. 2001;40:3002-8 pubmed
    ..This characteristic stands in direct contrast to the thermodynamic basis of the allosteric response in the homologous PFK from E. coli in which the sign of the coupling free energy is established by the sign of the coupling enthalpy. ..
  22. Pham A, Reinhart G. Pre-steady state quantification of the allosteric influence of Escherichia coli phosphofructokinase. J Biol Chem. 2001;276:34388-95 pubmed
    ..Furthermore, both phosphoenolpyruvate and MgADP act by influencing the fast complex formation step while leaving the slower enzyme isomerization step essentially unchanged. ..
  23. Davidson S, Burnett M, Hoffman Goetz L. Training effects in mice after long-term voluntary exercise. Med Sci Sports Exerc. 2006;38:250-5 pubmed
    ..These findings suggest that wheel running in female C57BL/6 mice: 1) produces a measurable aerobic training effect and 2) is an effective exercise modality for long-term training studies. ..
  24. Tuininga J, Verhees C, van der Oost J, Kengen S, Stams A, de Vos W. Molecular and biochemical characterization of the ADP-dependent phosphofructokinase from the hyperthermophilic archaeon Pyrococcus furiosus. J Biol Chem. 1999;274:21023-8 pubmed
    ..ATP and AMP were identified as competitive inhibitors of the phosphofructokinase, raising the K(m) for ADP to 0.34 and 0.41 mM, respectively...
  25. Cohen J, Atluri P, Taylor M, Grand T, Liao G, Panlilio C, et al. Fructose 1,6-diphosphate administration attenuates post-ischemic ventricular dysfunction. Heart Lung Circ. 2006;15:119-23 pubmed
    ..0 nmol/g ischemic tissue; p<0.0369). The administration of the glycolytic intermediate, FDP, by intravenous injection, resulted in significantly improved myocardial function after ischemia and improved bioenergetics during ischemia. ..
  26. Russell P, Williams A, Marquez K, Hua T, Ehya F, Hardamon C, et al. Effect of ammonium, sodium, and potassium ions on rabbit muscle phosphofructokinase-1 and adenylate kinase activities. J Enzyme Inhib Med Chem. 2009;24:930-6 pubmed publisher
    ..These attributes are discussed as they may relate to the role of ascorbate facilitation glycogen synthesis in resting muscle and the role that the cytoskeleton infrastructure scaffold may play is also discussed. ..
  27. Tian K, Lin J, Liu X, Liu Y, Zhang C, Yan W. Conversion of an obligate autotrophic bacteria to heterotrophic growth: expression of a heterogeneous phosphofructokinase gene in the chemolithotroph Acidithiobacillus thiooxidans. Biotechnol Lett. 2003;25:749-54 pubmed
    ..coli (K12: 86 U g-1; DF1010 carrying plasmid pSDK-1: 97 U g-1). In the presence of glucose, the Tt-7 transconjugant consumed glucose leading to a better growth yield. ..
  28. Marcondes M, Sola Penna M, Zancan P. Clotrimazole potentiates the inhibitory effects of ATP on the key glycolytic enzyme 6-phosphofructo-1-kinase. Arch Biochem Biophys. 2010;497:62-7 pubmed publisher
    ..Altogether, the results presented here suggest that PFK inhibition by CTZ involves a decrease in the affinity of PFK for its substrates at the catalytic site with the concomitant potentiation of the inhibitory properties of ATP. ..
  29. Nichols R, Rudolphi O, Ek B, Exelbert R, Plotz P, Raben N. Glycogenosis type VII (Tarui disease) in a Swedish family: two novel mutations in muscle phosphofructokinase gene (PFK-M) resulting in intron retentions. Am J Hum Genet. 1996;59:59-65 pubmed
    ..Both mutations are predicted to result in premature termination of translation. Some of the transcripts generated from the intron 16 mutated allele also contain intron 10 sequence unspliced...
  30. Rider M, Kuntz D, Hue L. Fructose 2,6-bisphosphate and its phosphorothioate analogue. Comparison of their hydrolysis and action on glycolytic and gluconeogenic enzymes. Biochem J. 1988;253:597-601 pubmed
    ..The analogue was twice as effective as authentic fructose 2,6-bisphosphate in stimulating pyruvate kinase from trypanosomes. ..
  31. Andres V, Carreras J, Cusso R. Activation of muscle phosphofructokinase by alpha-glucose 1,6-bisphosphate and fructose 2,6-bisphosphate is differently affected by other allosteric effectors and by pH. Biochem Biophys Res Commun. 1988;157:664-9 pubmed
    ..This suggest that both alpha-glucose 1,6-bisphosphate and fructose 1,6-bisphosphate induce the same conformational change on muscle phosphofructokinase, distinct from that produced by fructose 2,6-bisphosphate. ..
  32. Canesi L, Borghi C, Fabbri R, Ciacci C, Lorusso L, Gallo G, et al. Effects of 17beta-estradiol on mussel digestive gland. Gen Comp Endocrinol. 2007;153:40-6 pubmed
  33. Dourmashkin J, Chang G, Gayles E, Hill J, Fried S, Julien C, et al. Different forms of obesity as a function of diet composition. Int J Obes (Lond). 2005;29:1368-78 pubmed
    ..These results suggest the existence of multiple forms of obesity with different underlying mechanisms that are diet dependent. ..
  34. Thomas C, Bishop D, Moore Morris T, Mercier J. Effects of high-intensity training on MCT1, MCT4, and NBC expressions in rat skeletal muscles: influence of chronic metabolic alkalosis. Am J Physiol Endocrinol Metab. 2007;293:E916-22 pubmed
    ..The correlation between MCT1 and NBC expression suggests that lactate transport may be facilitated by NBC in oxidative skeletal muscle, which may in turn favor better muscle pH regulation. ..
  35. Sabnis N, Yang H, Romeo T. Pleiotropic regulation of central carbohydrate metabolism in Escherichia coli via the gene csrA. J Biol Chem. 1995;270:29096-104 pubmed
    ..In contrast, the expression of genes of the pentose phosphate pathway was weakly or negligibly affected by csrA. ..
  36. Huerta Beristain G, Utrilla J, Hernández Chávez G, Bolivar F, Gosset G, Martinez A. Specific ethanol production rate in ethanologenic Escherichia coli strain KO11 Is limited by pyruvate decarboxylase. J Mol Microbiol Biotechnol. 2008;15:55-64 pubmed publisher
    ..This experimental metabolic control analysis showed that ethanol flux in KO11 is negatively controlled by phosphofructokinase and pyruvate kinase, and positively influenced by the PDC(Zm) activity level. ..
  37. Valdez B, Chen Z, Sosa M, Younathan E, Chang S. Human 6-phosphofructo-1-kinase gene has an additional intron upstream of start codon. Gene. 1989;76:167-9 pubmed
    ..The available sequence of the two cDNAs shows 256 nt differences. Surprisingly, 71% of these sites are A's and T's in the human cDNA and C's and G's in the rabbit gene. ..
  38. Mediavilla D, Metón I, Baanante I. Purification and kinetic properties of 6-phosphofructo-1-kinase from gilthead sea bream muscle. Biochim Biophys Acta. 2007;1770:706-15 pubmed
    ..Unlike the mammalian muscle enzyme, our findings support that phosphorylation of PFKM may exert a major role during starvation in fish muscle. ..
  39. Heinisch J. PFK2, ISP42, ERG2 and RAD14 are located on the right arm of chromosome XIII. Yeast. 1993;9:1103-5 pubmed
    ..Four genes were shown to reside on this fragment, namely PFK2, ISP42, ERG2 and RAD14. PFK2 was mapped previously to the right arm of chromosome XIII, locating the latter three genes to the same chromosome. ..
  40. Kirchberger J, Bär J, Schellenberger W, Dihazi H, Kopperschläger G. 6-phosphofructokinase from Pichia pastoris: purification, kinetic and molecular characterization of the enzyme. Yeast. 2002;19:933-47 pubmed
    ..Sequencing of the N-terminus (VTKDSIXRDLEXENXGXXFF) and of peptide fragments by applying MALDI-TOF PSD, m/z 1517.3 (DAMNVVNH) and m/z 2177.2 [AQNCNVC(L/I)SVHEAHTM] gave no relevant information about the identity of this protein. ..
  41. Marinho Carvalho M, Costa Mattos P, Spitz G, Zancan P, Sola Penna M. Calmodulin upregulates skeletal muscle 6-phosphofructo-1-kinase reversing the inhibitory effects of allosteric modulators. Biochim Biophys Acta. 2009;1794:1175-80 pubmed publisher
    ..In the end, we suggest that CaM binding to PFK, which is stimulated by Ca(2+), represents an important way to increase the glycolytic pathway in cells. ..
  42. Branny P, de la Torre F, Garel J. Cloning, sequencing, and expression in Escherichia coli of the gene coding for phosphofructokinase in Lactobacillus bulgaricus. J Bacteriol. 1993;175:5344-9 pubmed
    ..bulgaricus, the coordinated regulation of phosphofructokinase and pyruvate kinase occurs at the levels of both biosynthesis and enzymatic activity...
  43. Canesi L, Betti M, Ciacci C, Gallo G. Insulin-like effect of zinc in mytilus digestive gland cells: modulation of tyrosine kinase-mediated cell signaling. Gen Comp Endocrinol. 2001;122:60-6 pubmed
    ..These data underline the importance of cross talk between different MAPKs in determination of the response to extracellular stimuli in marine invertebrate cells. ..
  44. Schirmer T, Evans P. Structural basis of the allosteric behaviour of phosphofructokinase. Nature. 1990;343:140-5 pubmed
    ..These concerted changes link all the substrate and effector sites in the tetramer, and explain the change of affinity for the cooperative substrate. ..
  45. Le Bras G, Deville Bonne D, Garel J. Purification and properties of the phosphofructokinase from Lactobacillus bulgaricus. A non-allosteric analog of the enzyme from Escherichia coli. Eur J Biochem. 1991;198:683-7 pubmed
  46. Xu T, Bai Z, Wang L, He B. Breeding of D(-)-lactic acid high producing strain by low-energy ion implantation and preliminary analysis of related metabolism. Appl Biochem Biotechnol. 2010;160:314-21 pubmed publisher
    ..These might be affected by ion beam implantation. ..
  47. Kowallik W, Thiemann M, Huang Y, Mutumba G, Beermann L, Broer D, et al. Complete sequence of glycolytic enzymes in the mycorrhizal basidiomycete, Suillus bovinus. Z Naturforsch C. 1998;53:818-27 pubmed
    ..5-8.0. Triosephosphate isomerase and pyruvate kinase showed highest activities at pH 6.5. Regulatory sites within the glycolytic pathway of Suillus bovinus are discussed; fructose 6-phosphate kinase appears to be its main bottle neck. ..
  48. Tsujino S, Servidei S, Tonin P, Shanske S, Azan G, DiMauro S. Identification of three novel mutations in non-Ashkenazi Italian patients with muscle phosphofructokinase deficiency. Am J Hum Genet. 1994;54:812-9 pubmed
  49. Brito S, Moura M, Kawashita N, Brito M, Kettelhut I, Migliorini R. Glucose uptake and glycolytic flux in adipose tissue from rats adapted to a high-protein, carbohydrate-free diet. Metabolism. 2001;50:1208-12 pubmed
    ..The low-plasma insulin and high-glucagon levels in HP-fed rats may have played an important role in the reduction of adipose tissue glucose utilization in these animals. ..
  50. Ristow M, Vorgerd M, Mohlig M, Schatz H, Pfeiffer A. Deficiency of phosphofructo-1-kinase/muscle subtype in humans impairs insulin secretion and causes insulin resistance. J Clin Invest. 1997;100:2833-41 pubmed
    ..These combined metabolic sequelae of PFK-1 deficiency identify it as a candidate gene predisposing to NIDDM. ..
  51. Gunasekera D, Kemp R. Genomic organization, 5'flanking region and tissue-specific expression of mouse phosphofructokinase C gene. Gene. 2000;260:103-12 pubmed
    ..Based on the mouse PFK-C signal normalized to 18S rRNA, the PFK-C mRNA was expressed at the highest levels in the brain, heart, thymus and testicles, whereas low levels were observed in the kidney, liver, muscle, and lung. ..
  52. Almeida A, Moncada S, Bolanos J. Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructo-2-kinase pathway. Nat Cell Biol. 2004;6:45-51 pubmed
    ..Thus the virtual absence of PFK2 in neurons may explain their extreme sensitivity to energy depletion and degeneration. ..
  53. Kaetzke A, Eschrich K. Simultaneous determination of different DNA sequences by mass spectrometric evaluation of Sanger sequencing reactions. Nucleic Acids Res. 2002;30:e117 pubmed
    ..Short sequences with a length between 21 and 25 nt were sufficient to reflect the heterogeneity of the 16S rDNA genes in E.coli and the existence of three isoenzymes of PFK-1 in rat brain. ..