Difference between revisions of "Phosphofructokinase type 1"
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* The <math>\alpha</math> and <math>\beta</math> in the rate equation represents the factors by which the ligand affinity and catalytic capacity are modified in the presence of an allosteric activatory <ref name="moreno_2012">R. Moreno-Sánchez, A. Marín-Hernández, J.C. Gallardo-Pérez, H. Quezada, R. Encalada, S. Rodríguez-Enríquez ''et al.'' (2012), ''Phosphofructokinase type 1 kinetics, isoform expression, and gene polymorphisms in cancer cells'', J Cell Biochem, 113, pp. 1692–1703</ref>. As <math>Fru2,6BP</math> is the only activator in our model we considered the <math>\alpha</math> and <math>\beta</math> value of <math>Fru2,6BP</math>, <math>\alpha_{Fru2,6BP} = 0.75\pm 0.4</math> and <math>\beta_{Fru2,6BP} = 1.18\pm 0.17</math>. These two values are measured in the presence of 140 <math>\text{mM K}^{+}</math> medium <ref name="moreno_2012"></ref>. | * The <math>\alpha</math> and <math>\beta</math> in the rate equation represents the factors by which the ligand affinity and catalytic capacity are modified in the presence of an allosteric activatory <ref name="moreno_2012">R. Moreno-Sánchez, A. Marín-Hernández, J.C. Gallardo-Pérez, H. Quezada, R. Encalada, S. Rodríguez-Enríquez ''et al.'' (2012), ''Phosphofructokinase type 1 kinetics, isoform expression, and gene polymorphisms in cancer cells'', J Cell Biochem, 113, pp. 1692–1703</ref>. As <math>Fru2,6BP</math> is the only activator in our model we considered the <math>\alpha</math> and <math>\beta</math> value of <math>Fru2,6BP</math>, <math>\alpha_{Fru2,6BP} = 0.75\pm 0.4</math> and <math>\beta_{Fru2,6BP} = 1.18\pm 0.17</math>. These two values are measured in the presence of 140 <math>\text{mM K}^{+}</math> medium <ref name="moreno_2012"></ref>. | ||
− | * The Vm value is reported as <math>56 \pm 23</math> ( | + | * The Vm value is reported as <math>56 \pm 23</math> U(mg protein)^{-1}. HeLa cells were harvested at a concentration of 65 mg protein/ml <ref name="moreno_2012"></ref>. Converting Vm to mM/min becomes <math> 0.0364 \pm 0.01495 </math> again in the presence of 140 <math>\text{mM K}^{+}</math>. |
*<math>Km_{ADP} = 1.4</math> for ''Thermotoga maritima'' is being reported in Hansen, T., M. Musfeldt ''et. al.'' <ref name="Hansen">Hansen, T., M. Musfeldt, and P. Schonheit (2002), ''ATP-dependent 6-phosphofructokinase from the hyperthermophilic bacterium Thermotoga maritima: characterization of an extremely thermophilic, allosterically regulated enzyme''. Arch. Microbiol. 177:401-409 </ref> and <math>Km_{Fru1,6BP} = 16.7</math> for ''Desulfurococcus amylolyticus'' is reported in Hansen T, Schönheit P. ''et. al.''<ref name="Hansen_2003">Hansen T, Schönheit P. (2003),''Purification and Characterization of the MQH2:NO Oxidoreductase from the Hyperthermophilic Archaeon Pyrobaculum aerophilum'', J Biol Chem, 278 (38), 35861-35868 </ref>. The mean and std. dev. is calculated as <math>0.945 \pm 0.454</math> | *<math>Km_{ADP} = 1.4</math> for ''Thermotoga maritima'' is being reported in Hansen, T., M. Musfeldt ''et. al.'' <ref name="Hansen">Hansen, T., M. Musfeldt, and P. Schonheit (2002), ''ATP-dependent 6-phosphofructokinase from the hyperthermophilic bacterium Thermotoga maritima: characterization of an extremely thermophilic, allosterically regulated enzyme''. Arch. Microbiol. 177:401-409 </ref> and <math>Km_{Fru1,6BP} = 16.7</math> for ''Desulfurococcus amylolyticus'' is reported in Hansen T, Schönheit P. ''et. al.''<ref name="Hansen_2003">Hansen T, Schönheit P. (2003),''Purification and Characterization of the MQH2:NO Oxidoreductase from the Hyperthermophilic Archaeon Pyrobaculum aerophilum'', J Biol Chem, 278 (38), 35861-35868 </ref>. The mean and std. dev. is calculated as <math>0.945 \pm 0.454</math> |
Revision as of 12:56, 22 September 2014
The enzyme Phosphofructokinase Type-1 uses another ATP molecule to transfer a phosphate group to Fru6P to form fructose 1, 6-bisphosphate. PFK-1 is an allosteric enzyme showing cooperative behaviour with Fru6P and hyperbolic kinetics with ATP.
Contents
Chemical equation
![Fru6P + ATP \rightleftharpoons Fru1,6BP + ADP](/wiki/images/math/f/9/3/f931feed721084327fc70fe25f43784b.png)
Rate equation
The concerted transition model of Monod, Wyman and Changeux (MWC model) is used as a rate equation for this tetrameric enzyme for considering exclusive ligand binding (F6P, activators and inhibitors) together with mixed type activation, (Fru2,6BP or AMP or Pi) [1].
![v = Vm \left(\frac{\frac{[ATP]}{Km_{ATP}}}{1 + \frac{[ATP]}{Km_{ATP}} }\right ) \left ( \frac{ 1 + \frac{\beta[Fru2,6BP]}{ \alpha Ka_{Fru2,6BP} } }{ 1 + \frac{[Fru2,6BP]}{ \alpha Ka_{Fru2,6BP} } } \right )
\left( \frac{\frac{[Fru6P]\left(1+\frac{[Fru2,6BP]}{[\alpha Ka_{Fru2,6BP}]}\right)}{Km_{Fru6P}\left(1 + \frac{[Fru2,6BP]}{Ka_{Fru2,6BP}}\right)} \left[1 + \frac{[Fru6P]\left(1+\frac{[Fru2,6BP]}{\alpha Ka_{Fru2,6BP}}\right)}{Km_{Fru6P}\left(1 + \frac{[Fru2,6BP]}{Ka_{Fru2,6BP}}\right)} \right]^3}
{ \frac{L\left( 1 + \frac{[CIT]}{Ki_{CIT}}\right)^4\left(1 + \frac{[ATP]}{Ki_{ATP}}\right)^4}{\left(1+\frac{[Fru2,6BP]}{Ka_{Fru2,6BP}}\right)^4} + \left[1 + \frac{Fru6P\left(1+\frac{Fru2,6BP}{\alpha Ka_{Fru2,6BP}}\right)}{Km_{Fru6P}\left(1 + \frac{[Fru2,6BP]}{Ka_{Fru2,6BP}}\right)} \right]^4 } - \left( \frac{\frac{[ADP][Fru1,6BP]}{K_{ADP}K_{Fru1,6BP}K_{eq}}}{\frac{[ADP]}{K_{ADP}} + \frac{[Fru1,6BP]}{K_{Fru1,6BP}} + \frac{[ADP][Fru1,6BP]}{K_{ADP}K_{Fru1,6BP}} + 1 } \right) \right)](/wiki/images/math/9/b/0/9b0e838e3bb1a1ed51a5745253a99625.png)
Parameter values
Parameter | Value | Units | Organism | Remarks |
---|---|---|---|---|
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0.031 [1] | ![]() |
HeLa cell line | Moreno-Sánchez, Marín-Hernández, Encalada & Saavedra, unpublished results |
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1.0 [1] | mM | ||
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0.021[1] | mM | ||
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20[1] | mM | ||
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6.8[1] | mM | ||
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mM | ||
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0.32[1] | Dimensionless | ||
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0.98[1] | Dimensionless | ||
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4.1[1] | Dimensionless | ||
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5[1] | mM | ||
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5[1] | mM | ||
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247[1] | mM | Recalculated from the ![]() |
Parameters with uncertainty
- The
and
in the rate equation represents the factors by which the ligand affinity and catalytic capacity are modified in the presence of an allosteric activatory [2]. As
is the only activator in our model we considered the
and
value of
,
and
. These two values are measured in the presence of 140
medium [2].
- The Vm value is reported as Failed to parse (Cannot store math image on filesystem.): 56 \pm 23
U(mg protein)^{-1}. HeLa cells were harvested at a concentration of 65 mg protein/ml [2]. Converting Vm to mM/min becomes Failed to parse (Cannot store math image on filesystem.): 0.0364 \pm 0.01495
again in the presence of 140
.
for Thermotoga maritima is being reported in Hansen, T., M. Musfeldt et. al. [3] and
for Desulfurococcus amylolyticus is reported in Hansen T, Schönheit P. et. al.[4]. The mean and std. dev. is calculated as
- Similarly for
in Thermotoga maritima is being reported in Hansen, T., M. Musfeldt et. al. [3] and
in Desulfurococcus amylolyticus is reported in Hansen T, Schönheit P. et. al.[4]. The mean and std. dev. is calculated as
- Four Keq values have been reported in the SilicoTrypWiki (Wikipedia for insilico modelling of Trypanosome) for Phosphofructokinase: 308.4, 254, 1035, 800[5]. As the
value does not depend on the organism, the mean and the standard deviation can be calculated from these 4 values collected for Trypanosome.[6]. The mean and std. dev. of this value is
Parameter | Value | Units | Organism |
---|---|---|---|
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Failed to parse (Cannot store math image on filesystem.): 0.0364 \pm 0.01495 | ![]() |
HeLa Cell line |
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mM | HeLa Cell line |
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mM | HeLa Cell line |
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mM | Human muscle |
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mM | HeLa Cell line |
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mM | HeLa Cell line |
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Dimensionless | HeLa Cell line |
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Dimensionless | HeLa Cell line |
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Dimensionless | HeLa Cell line |
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mM | Thermotoga maritima & Desulfurococcus amylolyticus |
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mM | Thermotoga maritima & Desulfurococcus amylolyticus |
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Trypanosome |
Equilibrium constant
Equilibrium constant | Conditions | Source |
---|---|---|
308.4 | pH=7, T=25°C | Lehninger, (2008)[8] p 553:
|
254 | pH=7, T=25°C | Lehninger, (1975)[9] p 396. |
1035 | pH=7, T=25°C | Voet et al.[10] from Newshole et al. (1973) [11]p 97:
|
800 | T=298.15 K; pH=7.0; Method: calorimetry; Buffer: Tris (0.1 mol dm-3) + HCl. | NIST database "Thermodynamics of Enzyme-Catalyzed Reactions" entry [75BOH/SCH_551] from Bvhme et al. (1975)[12] |
- The Average from these values are
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 Marín-Hernández A, Gallardo-Pérez JC, Rodríguez-Enríquez S et al (2011). Modeling cancer glycolysis. Biochim Biophys Acta, 1807:755–767 (doi)
- ↑ 2.0 2.1 2.2 2.3 R. Moreno-Sánchez, A. Marín-Hernández, J.C. Gallardo-Pérez, H. Quezada, R. Encalada, S. Rodríguez-Enríquez et al. (2012), Phosphofructokinase type 1 kinetics, isoform expression, and gene polymorphisms in cancer cells, J Cell Biochem, 113, pp. 1692–1703
- ↑ 3.0 3.1 Hansen, T., M. Musfeldt, and P. Schonheit (2002), ATP-dependent 6-phosphofructokinase from the hyperthermophilic bacterium Thermotoga maritima: characterization of an extremely thermophilic, allosterically regulated enzyme. Arch. Microbiol. 177:401-409
- ↑ 4.0 4.1 Hansen T, Schönheit P. (2003),Purification and Characterization of the MQH2:NO Oxidoreductase from the Hyperthermophilic Archaeon Pyrobaculum aerophilum, J Biol Chem, 278 (38), 35861-35868
- ↑ [Silicotryp]
- ↑ F. Achcar, E.J. Kerkhoven, B.M. Bakker, M.P. Barrett, R. Breitling (2012), Dynamic modelling under uncertainty: the case of Trypanosoma brucei energy metabolism, PLoS Comput Biol, 8, p. e1002352
- ↑ Brueser, A.; Kirchberger, J.; Kloos, M.; Straeter, N.; Schoeneberg, T. (2012), Functional linkage of adenine nucleotide binding sites in mammalian muscle 6-phosphofructokinase, J. Biol. Chem. 287, 17546-17553 (2012)
- ↑ David L. Nelson, Michael M. Cox (2008), Lehninger Principles of Biochemistry (5th edn), W. H. Freeman and Company
- ↑ Lehninger, A.L. (1975) Biochemistry (2nd edn), Worth
- ↑ Voet, D., Voet., J.G. and Pratt, C. W. (1999) Fundamentals of biochemistry, Wiley
- ↑ Newshole, E.A. and Stuart, C. (1973) Regulation in Metabolism, Wiley
- ↑ Bvhme, H.-J., Schellenberger, W. and Hofmann, E. (1975) Acta Biol. Med. Germ. 34(1):15-20. (pmid: 241184)