Hexose-6-phosphate isomerase

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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.

Chemical reaction

Glc6P \rightleftharpoons Fru6P

Rate equation

Reversible competitive inhibition with Ery4P, 6PG and FBP. [1]

Failed to parse (Cannot store math image on filesystem.): \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}} }

Substituting with Haldane equation to ensure thermodynamic consistency we have

Failed to parse (syntax error): V_{mf}\frac{\left(1 - \frac{[Fru6P]}{K_{eq}[Glc6P]} }{ 1 + \frac{[Glc6P]}{Km_{Glc6P}} + \frac{[Fru6P]}{Km_{Fru6P}} + \frac{[ERY4P]}{Ki_{ERY4P}} + \frac{[6PG]}{Ki_{6PG}} + \frac{[Fru1,6BP]}{Ki_{Fru1,6BP}} }

Parameter values

Parameter Value Units Organism Remarks
V_{mf} 0.4 [1]  mM \times min^{-1} HeLa cell line 3 cell assays
V_{mr} 0.9[1]  mM \times min^{-1} 1 cell assay
Km_{Glc6P} 0.4  \pm 0.03 mM[1] mM 3 cell assays
Km_{Fru6P} 0.05[1] mM 2 cell assays
Ki_{ERY4P} 0.001[1] mM Adjusted in the interval based on activity
Ki_{Fru1,6BP} 0.06[1] mM Adjusted in the interval based on activity
Ki_{6PG} 0.015[1] mM Adjusted in the interval based on activity

Parameters with uncertainty

  • The uncertainty of V_{mr} and Km_{Fru6P} 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 Ki_{Ery4P}, Ki_{Fru1,6BP} and Ki_{6PG} are the averaged from the forward and reverse reaction value listed in Table S6 [1].
  • The uncertainty for Ki_{Ery4P} in HeLa cell line is mentioned in the forward reaction as 1 \pm 0.07 \mu M and in the reverse direction as 0.86 \mu M. The mean value is calcualated as \frac{1 + 0.86}{2} \mu M and the standard deviation is calculated based on the same ratio mentioned in forward reaction which comes as 0.00093 \pm 0.000063 in mM.
  • Same principle is used for Ki_{6PG}. The mean value is  \frac{0.0176+0.0155}{2} = 0.017 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 Ki_{Fru1,6BP}; 0.1[2], 0.06[1]. The mean and standard deviation are calcualted from these two values.
Parameter Value Units
V_{mf} 1.2 \pm 0.2  mM \times min^{-1}
V_{mr} Failed to parse (Cannot store math image on filesystem.): 2.8 \pm 0.9058  mM \times min^{-1}
Km_{Glc6P} 0.4 \pm 0.03 mM mM
Km_{Fru6P} 0.05 \pm 0.0214 mM
Ki_{ERY4P} 0.0009 \pm 0.000063 mM
Ki_{Fru1,6BP} 0.08 \pm 0.02 mM
Ki_{6PG} 0.017 \pm 0.0043 mM

Refences

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 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> tag; name "Hernandez2011" defined multiple times with different content Cite error: Invalid <ref> tag; name "Hernandez2011" defined multiple times with different content
  2. 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