Difference between revisions of "Fructose 1,6 bisphosphate aldolase"

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(→‎Equilibrium constant)
(→‎Parameters with uncertainty)
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==Parameters with uncertainty==
 
==Parameters with uncertainty==
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*The value for <math>V_{mf}</math> is collected from Hernandez ''et. al.'' <ref name="Hernandez_2006"></ref>. The <math>V_{mr}</math> is calcualted from the sampled <math>V_{mr}</math>, <math>Km_{Gly3P}</math>, <math>Km_{DHAP}</math> and <math>K_{eq}</math> values using the Haldane equation. '''Alternatively''' the reported value from AS-30D can be considered. The standard deviation can be calculated based on the same ratio of <math>V_{mf}</math>. However, as it is from a different species an extra 20% of uncertainty will be added. This gives the value <math>V_{mf}=0.063 \pm 0.028 </math>
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*The value for <math>V_{mf}</math> is collected from Hernandez ''et. al.'' <ref name="Hernandez_2006"></ref>. The <math>V_{mr}</math> is calcualted from the sampled <math>V_{mf}</math>, <math>Km_{Gly3P}</math>, <math>Km_{DHAP}</math> and <math>K_{eq}</math> values using the Haldane equation. '''Alternatively''' the reported value from AS-30D can be considered. The standard deviation can be calculated based on the same ratio of <math>V_{mf}</math>. However, as it is from a different species an extra 20% of uncertainty will be added. This gives the value <math>V_{mf}=0.063 \pm 0.028 </math><math>U\cdot(\text{mg protein})^{-1}</math>. Converting these value to <math>mM\cdot(min)^{-1}</math> gives 0.013 <math>mM\cdot(min)^{-1}</math>. But in the model they used the value of 0.08 <math>mM\cdot(min)^{-1}</math>. Considering these values the value of <math>V_{mf}</math> is
  
 
*The value for <math>Km_{Fru1,6BP}, Km_{Gly3P}, Km_{DHAP}</math>  are collected from Ali D. Malay ''et. al.'' <ref name="Ali">Malay AD, Procious SL, Tolan DR. (2002). ''The temperature dependence of activity and structure for most prevalent mutant aldolase B associated with hereditary fructose intolerance'', Arch BiochemBiophys 408: 295–304.</ref> for wildtype Aldolase B gene at <math>30^{\circ}</math>C.
 
*The value for <math>Km_{Fru1,6BP}, Km_{Gly3P}, Km_{DHAP}</math>  are collected from Ali D. Malay ''et. al.'' <ref name="Ali">Malay AD, Procious SL, Tolan DR. (2002). ''The temperature dependence of activity and structure for most prevalent mutant aldolase B associated with hereditary fructose intolerance'', Arch BiochemBiophys 408: 295–304.</ref> for wildtype Aldolase B gene at <math>30^{\circ}</math>C.
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|<math>V_{mf}</math>
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|<math>0.2 \pm 0.05 (5) </math> <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>
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|<math>0.0465 \pm 0.047 (5) </math> <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>
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|Sampled based on Haldane equation. <br> '''Alternative:'''<math>0.063 \pm 0.028 </math>
 
|Sampled based on Haldane equation. <br> '''Alternative:'''<math>0.063 \pm 0.028 </math>
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|<math> mM \times min^{-1} </math>
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Revision as of 13:05, 22 September 2014

This enzyme splits fructose 1, 6-bisphosphate into two sugars that are isomers of each other. These two sugars are Dihydroxyacetone phosphate (DHAP) and Glyceraldehyde 3-phosphate (Gly3P).

Chemical equation

Fru1,6BP \rightleftharpoons Gly3P + DHAP

Rate equation

Reversible Uni-Bi Michaelis-Menten is used. [1]

\frac{V_{mf} \frac{[Fru1,6BP]}{K_{Fru1,6BP}} - V_{mr}\frac{[DHAP][G3P]}{K_{DHAP}K_{Gly3P}} }{1 + \frac{[Fru1,6BP]}{K_{Fru1,6BP}} + \frac{[DHAP]}{K_{DHAP}} +\frac{[Gly3P]}{K_{Gly3P}} + \frac{[DHAP][Gly3P]}{K_{DHAP}K_{Gly3P}} }

Modified rate law to take into consideration the equilibrium constant

\frac{V_{mf} \frac{[Fru1,6BP]}{K_{Fru1,6BP}} \left(1- \frac{[DHAP][Gly3P]}{K_{eq}[Fru1,6BP]} \right)}{1 + \frac{[Fru1,6BP]}{K_{Fru1,6BP}} + \frac{[DHAP]}{K_{DHAP}} +\frac{[Gly3P]}{K_{Gly3P}} + \frac{[DHAP][Gly3P]}{K_{DHAP}K_{Gly3P}} }

Parameters

Parameter Value Units Organism Remarks
V_{mf} 0.08 [2] mM \times min^{-1} Hela cell line
V_{mr} 0.063[2] mM \times min^{-1} Rodent AS-30D hepatoma
Km_{Fru1,6BP} 0.009[2] mM Hela cell line
Km_{Gly3P} 0.16[2] mM Rodent AS-30D hepatoma
Km_{DHAP} 0.08[2] mM Rodent AS-30D hepatoma

Parameters with uncertainty

  • The value for V_{mf} is collected from Hernandez et. al. [2]. The V_{mr} is calcualted from the sampled V_{mf}, Km_{Gly3P}, Km_{DHAP} and K_{eq} values using the Haldane equation. Alternatively the reported value from AS-30D can be considered. The standard deviation can be calculated based on the same ratio of V_{mf}. However, as it is from a different species an extra 20% of uncertainty will be added. This gives the value V_{mf}=0.063 \pm 0.028 U\cdot(\text{mg protein})^{-1}. Converting these value to mM\cdot(min)^{-1} gives 0.013 mM\cdot(min)^{-1}. But in the model they used the value of 0.08 mM\cdot(min)^{-1}. Considering these values the value of V_{mf} is
  • The value for Km_{Fru1,6BP}, Km_{Gly3P}, Km_{DHAP} are collected from Ali D. Malay et. al. [3] for wildtype Aldolase B gene at 30^{\circ}C.
Parameter Value Units Organism Remarks
V_{mf} Failed to parse (Cannot store math image on filesystem.): 0.0465 \pm 0.047 (5) [2] U\cdot(\text{mg protein})^{-1} Hela cell line
V_{mr} Sampled based on Haldane equation.
Alternative:0.063 \pm 0.028 		U\cdot(\text{mg protein})^{-1}
Km_{Fru1,6BP} 0.0024 \pm 0.0004 mM Human cell
Km_{Gly3P} 0.48 \pm 0.15 mM Human cell
Km_{DHAP} 0.38 \pm 0.01 mM Human cell

Equilibrium constant

Equilibrium constant Conditions Source
0.10 pH=7, T=25°C Voet et al.[4] from Newshole et al. (1973) [5]p 97:

\Delta G' = 22.8\ kJ.mol^{-1}, Failed to parse (Cannot store math image on filesystem.): Keq = exp(-\frac{\Delta G'}{RT}) = exp(\frac{-22800}{8.31*298.15}) \approx 0.00010

0.067 pH=7, T=25°C Lehninger, (1975)[6] p 407:

\Delta G' = 23.8\ kJ.mol^{-1}, Failed to parse (Cannot store math image on filesystem.): Keq = exp(-\frac{\Delta G'}{RT}) = exp(\frac{-23800}{8.31*298.15}) \approx 6.7326E-005

  • Taking average of these two values give Failed to parse (Cannot store math image on filesystem.): 8.40E-005 \pm 0.000023

References

  1. ↑ Marín-Hernández A, Gallardo-Pérez JC, Rodríguez-Enríquez S et al (2011) Modeling cancer glycolysis. Biochim Biophys Acta 1807:755–767 (doi)
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 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)
  3. ↑ Malay AD, Procious SL, Tolan DR. (2002). The temperature dependence of activity and structure for most prevalent mutant aldolase B associated with hereditary fructose intolerance, Arch BiochemBiophys 408: 295–304.
  4. ↑ Voet, D., Voet., J.G. and Pratt, C. W. (1999) Fundamentals of biochemistry, Wiley
  5. ↑ Newshole, E.A. and Stuart, C. (1973) Regulation in Metabolism, Wiley
  6. ↑ Lehninger, A.L. (1975) Biochemistry (2nd edn), Worth
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