Difference between revisions of "Hexose-6-phosphate isomerase"
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Reversible competitive inhibition with Ery4P, 6PG and FBP. <ref name="Hernandez2011"> Marín-Hernández A, Gallardo-Pérez JC, Rodríguez-Enríquez S ''et. al.'' (2011). ''Modeling cancer glycolysis''. Biochim Biophys Acta 1807:755–767 ([http://dx.doi.org/10.1016/j.bbabio.2010.11.006 doi]) </ref> | Reversible competitive inhibition with Ery4P, 6PG and FBP. <ref name="Hernandez2011"> Marín-Hernández A, Gallardo-Pérez JC, Rodríguez-Enríquez S ''et. al.'' (2011). ''Modeling cancer glycolysis''. Biochim Biophys Acta 1807:755–767 ([http://dx.doi.org/10.1016/j.bbabio.2010.11.006 doi]) </ref> | ||
− | <center><math>\frac{V_{mf}\frac{[Glc6P]}{Km_{Glc6P}} - V_{mr} \frac{[Fru6P]}{Km_{Fru6P}} }{ 1 + \frac{[Glc6P]}{Km_{Glc6P}} + \frac{[Fru6P]}{Km_{Fru6P}} + \frac{[ERY4P]}{Ki_{ERY4P}} + \frac{[6PG]}{Ki_{6PG}} + \frac{[Fru1,6BP]}{Ki_{Fru1,6BP}} }</math></center> | + | <center><math>v=\frac{V_{mf}\frac{[Glc6P]}{Km_{Glc6P}} - V_{mr} \frac{[Fru6P]}{Km_{Fru6P}} }{ 1 + \frac{[Glc6P]}{Km_{Glc6P}} + \frac{[Fru6P]}{Km_{Fru6P}} + \frac{[ERY4P]}{Ki_{ERY4P}} + \frac{[6PG]}{Ki_{6PG}} + \frac{[Fru1,6BP]}{Ki_{Fru1,6BP}} }</math></center> |
+ | |||
+ | Substituting with Haldane equation to ensure thermodynamic consistency we have | ||
+ | |||
+ | <center><math>v= \frac{V_{mf}\frac{[Glc6P]}{Km_{Glc6P}}\left(1 - \frac{[Fru6P]}{K_{eq}[Glc6P]} \right)}{ 1 + \frac{[Glc6P]}{Km_{Glc6P}} + \frac{[Fru6P]}{Km_{Fru6P}} + \frac{[ERY4P]}{Ki_{ERY4P}} + \frac{[6PG]}{Ki_{6PG}} + \frac{[Fru1,6BP]}{Ki_{Fru1,6BP}} }</math></center> | ||
==Parameter values== | ==Parameter values== | ||
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==Parameters with uncertainty== | ==Parameters with uncertainty== | ||
[[Category:Uncertainty]] | [[Category:Uncertainty]] | ||
− | * The uncertainty of <math>V_{mr}</math> | + | * The V is measured in the reverse order for the enzyme (<math>V_{mr}</math>) in <ref name="Hernandez_2006"> Marín-Hernández A , Rodríguez-Enríquez S, Vital-González P A, ''et al.'' (2006). ''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., 273 , pp. 1975–1988([http://dx.doi.org/doi:10.1111/j.1742-4658.2006.05214.x doi]) </ref> as <math>3 \pm 1.7</math><math>U\cdot(\text{mg protein})^{-1}</math>. The <math>V_{mf}</math> is calculated based on Haldane equation. The same relative percent error for <math>V_{mr}</math> is used to define the uncertainty of this parameter. The value is <math>0.17 \pm 0.09</math> <math>U\cdot(\text{mg protein})^{-1}</math>. In the supplement of <ref name="Hernandez2011"> Marín-Hernández A, Gallardo-Pérez JC, Rodríguez-Enríquez S et al (2011) Modeling cancer glycolysis. Biochim Biophys Acta 1807:755–767 ([http://dx.doi.org/10.1016/j.bbabio.2010.11.006 doi]) </ref> the value is reported as 1.2 <math>U\cdot(\text{mg protein})^{-1}</math>. Same error ratio for <math>V_{mr}</math> reported in <ref name="Hernandez_2006"></ref> is used in the model. After necessary calculation for unit conversion, the value is then <math> 78 \pm 44.2 </math><math>mM\cdot(min)^{-1}</math> |
+ | |||
+ | *The uncertainty of <math>Km_{Fru6P}</math> for HeLa cell line are calculated based on the same proportion of uncertainty for AS-30D cell reported in the paper Marín-Hernández ''et. al.'', ''Modeling cancer glycolysis'' <ref name="Hernandez2011"></ref>. | ||
* The value of <math>Ki_{Ery4P}</math>, <math>Ki_{Fru1,6BP}</math> and <math>Ki_{6PG}</math> are the averaged from the forward and reverse reaction value listed in Table S6 <ref name="Hernandez2011"></ref>. | * The value of <math>Ki_{Ery4P}</math>, <math>Ki_{Fru1,6BP}</math> and <math>Ki_{6PG}</math> are the averaged from the forward and reverse reaction value listed in Table S6 <ref name="Hernandez2011"></ref>. | ||
− | * The uncertainty for <math>Ki_{Ery4P}</math> in HeLa cell line is mentioned in the forward reaction as <math>1 \pm 0.07\ | + | * The uncertainty for <math>Ki_{Ery4P}</math> in HeLa cell line is mentioned in the forward reaction as <math>1 \pm 0.07 \mu M</math> and in the reverse direction as <math>0.86 \mu M</math>. The mean value is calcualated as <math>\frac{1 + 0.86}{2} \mu M</math> and the standard deviation is calculated based on the same ratio mentioned in forward reaction which comes as <math>0.00093 \pm 0.000063</math> in mM. |
* Same principle is used for <math>Ki_{6PG}</math>. The mean value is <math> \frac{0.0176+0.0155}{2} = 0.017 </math> and the standard deviation is calculted based on the same ratio of reverse reaction for HeLa cell line; 0.0043 <math></math> | * Same principle is used for <math>Ki_{6PG}</math>. The mean value is <math> \frac{0.0176+0.0155}{2} = 0.017 </math> and the standard deviation is calculted based on the same ratio of reverse reaction for HeLa cell line; 0.0043 <math></math> | ||
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|- | |- | ||
|<math>V_{mf}</math> | |<math>V_{mf}</math> | ||
− | |<math> | + | |<math>78 \pm 44.2</math> |
− | |<math> mM \ | + | |<math> mM\cdot(min)^{-1} </math> |
|- | |- | ||
|<math>V_{mr}</math> | |<math>V_{mr}</math> | ||
− | |<math> | + | |<math>3 \pm 1.7 </math> |
− | |<math> | + | |<math>U\cdot(\text{mg protein})^{-1}</math> |
|- | |- | ||
|<math>Km_{Glc6P}</math> | |<math>Km_{Glc6P}</math> | ||
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|mM | |mM | ||
|} | |} | ||
+ | |||
+ | === Equilibrium constant === | ||
+ | {|class="wikitable" | ||
+ | ! Equilibrium constant | ||
+ | ! Conditions | ||
+ | ! Source | ||
+ | |- | ||
+ | | 0.50 | ||
+ | | pH=7, T=25°C | ||
+ | | Lehninger, (2008)<ref name="lehninger2008">David L. Nelson, Michael M. Cox (2008), Lehninger Principles of Biochemistry (5th edn), W. H. Freeman and Company</ref> p 553:<br/> | ||
+ | <math>\Delta G' = 1.7\ kJ.mol^{-1}</math>, <math>Keq = exp(-\frac{\Delta G'}{RT}) = exp(\frac{-1700}{8.31*298.15}) \approx 0.50</math> | ||
+ | |- | ||
+ | | 0.51 | ||
+ | | pH=7, T=25°C | ||
+ | | Lehninger, (1975)<ref name="lehninger75">Lehninger, A.L. (1975) Biochemistry (2nd edn), Worth</ref> p 396: Keq(reverse)=1.97 => Keq(forward)=1/1.97=0.51. | ||
+ | |- | ||
+ | | 0.41 | ||
+ | | pH=7, T=25°C | ||
+ | | Voet et al.<ref name="voet">Voet, D., Voet., J.G. and Pratt, C. W. (1999) Fundamentals of biochemistry, Wiley</ref> from Newshole et al. (1973) <ref name="newshole73">Newshole, E.A. and Stuart, C. (1973) Regulation in Metabolism, Wiley</ref>p 97:<br/> | ||
+ | <math>\Delta G' = 2.2\ kJ.mol^{-1}</math>, <math>Keq = exp(-\frac{\Delta G'}{RT}) = exp(\frac{-2200}{8.31*298.15}) \approx 0.41</math> | ||
+ | |} | ||
+ | |||
+ | *Averaging these values gives <math>0.47 \pm 0.05</math> | ||
==Refences== | ==Refences== | ||
<references/> | <references/> |
Latest revision as of 10:49, 16 October 2014
The enzyme Hexose-6-phosphate isomerase converts Glucose 6-phosphate (Glc6P) into its isomer Fructose 6-phosphate (Fru6P). Isomers have the same molecular formula, but the atoms of each molecule are arranged differently.
Contents
Chemical reaction
Rate equation
Reversible competitive inhibition with Ery4P, 6PG and FBP. [1]
Substituting with Haldane equation to ensure thermodynamic consistency we have
Parameter values
Parameter | Value | Units | Organism | Remarks |
---|---|---|---|---|
0.4 [1] | HeLa cell line | 3 cell assays | ||
0.9[1] | 1 cell assay | |||
0.4 0.03 mM[1] | mM | 3 cell assays | ||
0.05[1] | mM | 2 cell assays | ||
0.001[1] | mM | Adjusted in the interval based on activity | ||
0.06[1] | mM | Adjusted in the interval based on activity | ||
0.015[1] | mM | Adjusted in the interval based on activity |
Parameters with uncertainty
- The V is measured in the reverse order for the enzyme () in [2] as . The is calculated based on Haldane equation. The same relative percent error for is used to define the uncertainty of this parameter. The value is . In the supplement of [1] the value is reported as 1.2 . Same error ratio for reported in [2] is used in the model. After necessary calculation for unit conversion, the value is then
- The uncertainty of for HeLa cell line are calculated based on the same proportion of uncertainty for AS-30D cell reported in the paper Marín-Hernández et. al., Modeling cancer glycolysis [1].
- The value of , and are the averaged from the forward and reverse reaction value listed in Table S6 [1].
- The uncertainty for in HeLa cell line is mentioned in the forward reaction as and in the reverse direction as . The mean value is calcualated as and the standard deviation is calculated based on the same ratio mentioned in forward reaction which comes as in mM.
- Same principle is used for . The mean value is and the standard deviation is calculted based on the same ratio of reverse reaction for HeLa cell line; 0.0043
- There are two reported value for ; 0.1[3], 0.06[1]. The mean and standard deviation are calcualted from these two values.
Parameter | Value | Units |
---|---|---|
mM | mM | |
mM | ||
mM | ||
mM | ||
mM |
Equilibrium constant
Equilibrium constant | Conditions | Source |
---|---|---|
0.50 | pH=7, T=25°C | Lehninger, (2008)[4] p 553: , |
0.51 | pH=7, T=25°C | Lehninger, (1975)[5] p 396: Keq(reverse)=1.97 => Keq(forward)=1/1.97=0.51. |
0.41 | pH=7, T=25°C | Voet et al.[6] from Newshole et al. (1973) [7]p 97: , |
- Averaging these values gives
Refences
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 Marín-Hernández A, Gallardo-Pérez JC, Rodríguez-Enríquez S et. al. (2011). Modeling cancer glycolysis. Biochim Biophys Acta 1807:755–767 (doi) Cite error: Invalid
<ref>
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tag; name "Hernandez2011" defined multiple times with different content Cite error: Invalid<ref>
tag; name "Hernandez2011" defined multiple times with different content - ↑ 2.0 2.1 Marín-Hernández A , Rodríguez-Enríquez S, Vital-González P A, et al. (2006). 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., 273 , pp. 1975–1988(doi)
- ↑ Marin-Hernandez, A., Gallardo-Perez, J. C., Ralph, S. J., Rodriguez-Enriquez, S. & Moreno-Sanchez, R. (2009), HIF-1α modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms. Mini-Rev. Med. Chem. 9, 1084–1101
- ↑ 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