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Gene Review

PFK1  -  6-phosphofructokinase subunit alpha

Saccharomyces cerevisiae S288c

Synonyms: ATP-PFK, ATP-dependent 6-phosphofructokinase, ATP-dependent 6-phosphofructokinase subunit alpha, G8599, Phosphofructokinase 1, ...
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Disease relevance of PFK1

  • The deduced amino acid sequences showed: (i) 20% homology between the N- and the C-terminal halves of each subunit, (ii) 55% homology between the two subunits, and (iii) significant homologies to the PFK sequences from human and rabbit muscle (42%), Escherichia coli (34%), and Bacillus (36%) [1].
  • Deficiency of muscle PFK (PFK-M), glycogenosis type VII (Tarui disease), is an autosomal recessive disorder characterized by an exertional myopathy and hemolytic syndrome [2].
  • The phosphofructokinase from Spiroplasma citri, which has an Asp187, has been purified and its properties follow this pattern [3].
  • Epitope mapping of a monoclonal antibody directed against the alpha-subunit of phosphofructokinase-1 from Saccharomyces cerevisiae by screening phage display libraries [4].

High impact information on PFK1

  • The results agree with the predictions of an allosteric model for phosphofructokinase (EC; ATP:D-fructose-6-phosphate 1-phosphotransferase), which is the enzyme responsible for periodic operation of glycolysis [5].
  • When the mRNAs are ordered with respect to the glycolytic pathway, two peaks of maximal induction are observed at phosphofructokinase and pyruvate kinase [6].
  • By in vitro mutagenesis, we introduced this mutation in either PFK1 or PFK2 and found that the exchange in either subunit drastically reduced the sensitivity of the holoenzyme to ATP inhibition [7].
  • A mutation in the PFK1 gene, encoding the larger -subunits, rendering the enzyme insensitive to allosteric inhibition by ATP was found to be caused by an exchange of proline 728 for a leucine residue [7].
  • Yeast phosphofructokinase is a heterooctameric enzyme subject to a complex allosteric regulation [7].

Chemical compound and disease context of PFK1


Biological context of PFK1

  • The mutations are semidominant, do not complement one another, and define a gene PFK1 located 28-cm distal to rna1 on the extended right arm of chromosome XIII [10].
  • Plasmids containing the information of one or the other gene were identified by back-transformation into pfk single mutants (pfk1 PFK2, PFK1 pfk2) [11].
  • Single point mutations in either gene encoding the subunits of the heterooctameric yeast phosphofructokinase abolish allosteric inhibition by ATP [7].
  • Phosphofructokinase mutants of yeast. Biochemistry and genetics [10].
  • These data support the view that two gene duplication events occurred in the evolution of the yeast PFK genes [1].

Anatomical context of PFK1


Associations of PFK1 with chemical compounds

  • Other mutations that increase glucose-6-P, deletion of PFK1, which codes for the alpha-subunit of 6-phosphofructo-1-kinase, or of PGI1, the phosphoglucoisomerase gene, had similar effects on glycogen metabolism as did pfk2 mutants [16].
  • Here we provide data demonstrating that an alanine residue at positions 874 (for the PFK1-encoded alpha-subunit) or 868 (for the PFK2-encoded beta-subunit) is crucial to achieve this structure [17].
  • Physiological and metabolic analysis of the PFK1 PFK2 double mutant indicated that decreased Pf1k had no significant effect on growth, apparently due to compensatory increases in its positive effector, fructose 2,6-bisphosphate [18].
  • One gene, PFK1, has already been cloned and sequenced and the other one is the probable yeast gene coding for the beta-subunit of the succinyl-CoA synthetase [19].
  • All the glucose consumed by a double mutant lacking both P-fructokinase and 6-P-gluconate dehydrogenase ends up as 6-P-gluconate, yet the pfk1 mutants can glycolyze and grow on glucose in air [10].

Regulatory relationships of PFK1


Other interactions of PFK1


Analytical, diagnostic and therapeutic context of PFK1


  1. The phosphofructokinase genes of yeast evolved from two duplication events. Heinisch, J., Ritzel, R.G., von Borstel, R.C., Aguilera, A., Rodicio, R., Zimmermann, F.K. Gene (1989) [Pubmed]
  2. Functional expression of human mutant phosphofructokinase in yeast: genetic defects in French Canadian and Swiss patients with phosphofructokinase deficiency. Raben, N., Exelbert, R., Spiegel, R., Sherman, J.B., Nakajima, H., Plotz, P., Heinisch, J. Am. J. Hum. Genet. (1995) [Pubmed]
  3. The role of Glu187 in the regulation of phosphofructokinase by phosphoenolpyruvate. Auzat, I., Le Bras, G., Branny, P., De La Torre, F., Theunissen, B., Garel, J.R. J. Mol. Biol. (1994) [Pubmed]
  4. Epitope mapping of a monoclonal antibody directed against the alpha-subunit of phosphofructokinase-1 from Saccharomyces cerevisiae by screening phage display libraries. Hollborn, M., Kirchberger, J., Birkenmeier, G., Kopperschläger, G. J. Mol. Recognit. (1999) [Pubmed]
  5. Control of oscillating glycolysis of yeast by stochastic, periodic, and steady source of substrate: a model and experimental study. Boiteux, A., Goldbeter, A., Hess, B. Proc. Natl. Acad. Sci. U.S.A. (1975) [Pubmed]
  6. Yeast glycolytic mRNAs are differentially regulated. Moore, P.A., Sagliocco, F.A., Wood, R.M., Brown, A.J. Mol. Cell. Biol. (1991) [Pubmed]
  7. Single point mutations in either gene encoding the subunits of the heterooctameric yeast phosphofructokinase abolish allosteric inhibition by ATP. Rodicio, R., Strauss, A., Heinisch, J.J. J. Biol. Chem. (2000) [Pubmed]
  8. Application of mathematical tools for metabolic design of microbial ethanol production. Hatzimanikatis, V., Emmerling, M., Sauer, U., Bailey, J.E. Biotechnol. Bioeng. (1998) [Pubmed]
  9. Inorganic pyrophosphate: fructose-6-phosphate 1-phosphotransferase of the potato tuber is related to the major ATP-dependent phosphofructokinase of E. coli. Yuan, X.H., Kwiatkowska, D., Kemp, R.G. Biochem. Biophys. Res. Commun. (1988) [Pubmed]
  10. Phosphofructokinase mutants of yeast. Biochemistry and genetics. Lobo, Z., Maitra, P.K. J. Biol. Chem. (1983) [Pubmed]
  11. Isolation and characterization of the two structural genes coding for phosphofructokinase in yeast. Heinisch, J. Mol. Gen. Genet. (1986) [Pubmed]
  12. Assembly of phosphofructokinase-1 from Saccharomyces cerevisiae in extracts of single-deletion mutants. Klinder, A., Kirchberger, J., Edelmann, A., Kopperschläger, G. Yeast (1998) [Pubmed]
  13. Phosphofructokinase is responsible for the fructose 2,6-bisphosphate inhibition of hexokinase in tissue extracts. Niemeyer, H., Rabajille, E. Arch. Biochem. Biophys. (1988) [Pubmed]
  14. Glucose-induced microautophagy in Pichia pastoris requires the alpha-subunit of phosphofructokinase. Yuan, W., Tuttle, D.L., Shi, Y.J., Ralph, G.S., Dunn, W.A. J. Cell. Sci. (1997) [Pubmed]
  15. The chemical form of selenium affects insulinomimetic properties of the trace element: investigations in type II diabetic dbdb mice. Mueller, A.S., Pallauf, J., Rafael, J. J. Nutr. Biochem. (2003) [Pubmed]
  16. Glucose-6-P control of glycogen synthase phosphorylation in yeast. Huang, D., Wilson, W.A., Roach, P.J. J. Biol. Chem. (1997) [Pubmed]
  17. A single point mutation leads to an instability of the hetero-octameric structure of yeast phosphofructokinase. Kirchberger, J., Edelmann, A., Kopperschläger, G., Heinisch, J.J. Biochem. J. (1999) [Pubmed]
  18. Pyruvate kinase (Pyk1) levels influence both the rate and direction of carbon flux in yeast under fermentative conditions. Pearce, A.K., Crimmins, K., Groussac, E., Hewlins, M.J., Dickinson, J.R., Francois, J., Booth, I.R., Brown, A.J. Microbiology (Reading, Engl.) (2001) [Pubmed]
  19. Sequencing of a 9.9 kb segment on the right arm of yeast chromosome VII reveals four open reading frames, including PFK1, the gene coding for succinyl-CoA synthetase (beta-chain) and two ORFs sharing homology with ORFs of the yeast chromosome VIII. Guerreiro, P., Azevedo, D., Barreiros, T., Rodrigues-Pousada, C. Yeast (1997) [Pubmed]
  20. Suppression of pdc2 regulating pyruvate decarboxylase synthesis in yeast. Velmurugan, S., Lobo, Z., Maitra, P.K. Genetics (1997) [Pubmed]
  21. Functional complementation of yeast phosphofructokinase mutants by the non-allosteric enzyme from Dictyostelium discoideum. Estévez, A.M., Heinisch, J.J., Aragón, J.J. FEBS Lett. (1995) [Pubmed]
  22. Studies on the mechanism of the antifungal action of benzoate. Krebs, H.A., Wiggins, D., Stubbs, M., Sols, A., Bedoya, F. Biochem. J. (1983) [Pubmed]
  23. AMP deaminase reaction as a control system of glycolysis in yeast. Role of ammonium ion in the interaction of phosphofructokinase and pyruvate kinase activity with the adenylate energy charge. Yoshino, M., Murakami, K. J. Biol. Chem. (1985) [Pubmed]
  24. Biosynthesis and regulation of fructose-1,6-bisphosphatase and phosphofructokinase in Saccharomyces cerevisiae grown in the presence of glucose and gluconeogenic carbon sources. Foy, J.J., Bhattacharjee, J.K. J. Bacteriol. (1978) [Pubmed]
  25. Analysis of PFK3--a gene involved in particulate phosphofructokinase synthesis reveals additional functions of TPS2 in Saccharomyces cerevisiae. Sur, I.P., Lobo, Z., Maitra, P.K. Yeast (1994) [Pubmed]
  26. Temporal organization of the phosphofructokinase/fructose-1,6-biphosphatase cycle. Hofmann, E., Eschrich, K., Schellenberger, W. Adv. Enzyme Regul. (1985) [Pubmed]
  27. During the initiation of fermentation overexpression of hexokinase PII in yeast transiently causes a similar deregulation of glycolysis as deletion of Tps1. Ernandes, J.R., De Meirsman, C., Rolland, F., Winderickx, J., de Winde, J., Brandão, R.L., Thevelein, J.M. Yeast (1998) [Pubmed]
  28. Sequence analysis of the 43 kb CRM1-YLM9-PET54-DIE2-SMI1-PHO81-YHB4-PFK1 region from the right arm of Saccharomyces cerevisiae chromosome VII. van der Aart, Q.J., Kleine, K., Steensma, H.Y. Yeast (1996) [Pubmed]
  29. Interaction of 6-phosphofructokinase with cytosolic proteins of Saccharomyces cerevisiae. Schwock, J., Kirchberger, J., Edelmann, A., Kriegel, T.M., Kopperschläger, G. Yeast (2004) [Pubmed]
  30. Limited proteolysis of yeast phosphofructokinase. Sequence locations of cleavage sites created by the actions of different proteinases. Kopperschläger, G., Bär, J., Stellwagen, E. Eur. J. Biochem. (1993) [Pubmed]
  31. Rapid purification and crystallization of yeast phosphofructokinase. Welch, P., Scopes, R.K. Anal. Biochem. (1981) [Pubmed]
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