Difference between revisions of "Glucose Transporter"

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(Parameters with uncertainty)
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'''Alternative:''' The <math>K_{eq}</math> value of the transporters are reported to be 1.00.<ref name="Ettore">Ettore Murabito (2011), ''Application of Differential Metabolic Control Analysis to Identify New Targets in Cancer Treatment'', (PhD Thesis), University of Manchester</ref><ref name="Achcar_2012">F. Achcar, E.J. Kerkhoven, B.M. Bakker, M.P. Barrett, R. Breitling  (2012),
 
'''Alternative:''' The <math>K_{eq}</math> value of the transporters are reported to be 1.00.<ref name="Ettore">Ettore Murabito (2011), ''Application of Differential Metabolic Control Analysis to Identify New Targets in Cancer Treatment'', (PhD Thesis), University of Manchester</ref><ref name="Achcar_2012">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</ref>
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''Dynamic modelling under uncertainty: the case of Trypanosoma brucei energy metabolism'', PLoS Comput Biol, 8, p. e1002352</ref> As the <math>K_{eq}</math> is directly related to <math>K_{m}</math> values of substrate and product, the uncertainty would also be dependent. The highest uncertainty is mentioned for <math>K_{Glucose_{out}}</math> which is <math>70%</math> of the actual value. The same percentage of error is assumed for <math>K_{eq}</math>; <math>0.70</math>
 
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Revision as of 13:45, 23 May 2014

Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose over a plasma membrane. Glucose is a vital source of energy for all life.

Chemical equation

Glucose_{out} \rightleftharpoons Glucose_{in}

Rate equation

Mono-Substrate reversible Michaelis-Menten with Haldane substitution is used[1].

v = \frac{V_{mf}\Big([Glucose_{out}] - \frac{[Glucose_{in}]}{K_{eq}}\Big)}{K_{Glucose_{out}}\Big(1 + \frac{[Glucose_{in}]}{K_{Glucose_{in}}}\Big) + [Glucose_{out}]}

Parameter values

Parameter Value Units Organism Remarks
V_{mf} .017 [2]  \text{mM min}^{-1} HeLa cell line Vm is converted to  \text{mM min}^{-1} from U × (mg total cellular protein) at 37^{\circ}C
K_{eq} 1[3]
K_{Glucose_{in}} 9.3[2] mM
K_{Glucose_{out}} 10[3] mM

Parameters with uncertainty

Thirteen isoforms of Glucose transporter (GLUT) exist in Mammalian cells to facilitate the uptake of glucose from extracellular fluid into the cell. However, in most of the literature the kinetic properties of GLUT 1-4 isoforms are only reported [4][5]. In our model K_{m} value for the forward reaction is taken from the paper Modeling cancer glycolysis[1]. The mean and std. dev. of K_{m} for the reverse reaction is being averaged from the 4 isoforms of GLUT reported in Zhao et. al.[4].

Parameter Value Units Organism Remarks
V_{mf} 0.0172\pm 0.0064 [2]  \text{mM min}^{-1} HeLa cell line
K_{eq} K_{eq} value is sampled
based on the Haldane relation K_{eq} = \frac{V_{forward}*K_{product}}{V_{reverse}*K_{substrate}}[6]


Alternative: The K_{eq} value of the transporters are reported to be 1.00.[7][8] As the K_{eq} is directly related to K_{m} values of substrate and product, the uncertainty would also be dependent. The highest uncertainty is mentioned for K_{Glucose_{out}} which is 70% of the actual value. The same percentage of error is assumed for K_{eq}; 0.70

K_{Glucose_{in}}  9.3 \pm 3.3 [2] mM Multiple sites of human cell as 4 isoforms were considered
K_{Glucose_{out}} 8.0 \pm 5.64 [4] mM

References

  1. 1.0 1.1 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 Rodríguez-Enríquez S, Marín-Hernández A, Gallardo-Pérez J C, et. al.(2009). Kinetics of transport and phosphorylation of glucose in cancer cells. Journal of Cell. Physiology, 221 , pp. 552–559 (doi)
  3. 3.0 3.1 Arbitrary value
  4. 4.0 4.1 4.2 Zhao, F. and Keating, A. (2007), Functional Properties and Genomics of Glucose Transporters, Curr Genomics, 8(2), 113-128
  5. Medina RA, Meneses AM, Vera JC, Guzmán C, Nualart F, Rodriguez F, de los Angeles Garcia M, Kato S,Espinoza N, Monso C et al. (2004), Differential regulation of glucose transporter expression by estrogen and progesterone in Ishikawa endometrial cancer cells, J Endocrinol 182, 467–478.
  6. Alan Mellors (1976), The Haldane relationship enzymes and equilibrium, Biochemical Education, Volume 4, Issue 4, 71
  7. Ettore Murabito (2011), Application of Differential Metabolic Control Analysis to Identify New Targets in Cancer Treatment, (PhD Thesis), University of Manchester
  8. 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