Difference between revisions of "Monocarboxylate (Lactate) transporter"
(→Parameters with uncertainty) |
(→Equilibrium constant) |
||
Line 88: | Line 88: | ||
=== Equilibrium constant === | === Equilibrium constant === | ||
− | *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> 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> | + | *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> 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>.<br> |
+ | '''Alternative-2:''' In order to ensure that the uncertainty does not affect the model equilibrium a small uncertainty of 5% can be considered. In our model we have applied this approach. So <math>K_{eq} = 1 \pm 0.05</math> | ||
==References== | ==References== | ||
<references/> | <references/> |
Revision as of 14:53, 1 July 2014
Monocarboxylate transporters,[1] or MCTs, constitute a family of proton-linked plasma membrane transporters that carry molecules having one carboxylate group (monocarboxylates), such as lactate and pyruvate.
Contents
Chemical equation
Rate equation
Reversible Michaelis-Menten rate law is used
Modified rate law to take Thermodynamic constraint into consideration
Parameter values
Parameter | Value | Units | Organism | Remarks |
---|---|---|---|---|
2.5 [2] | Human tumor cells | |||
2.4 [3] | Rat liver cells | |||
4.5 [3] | mM | Rat liver cell | ||
4.54 [2] | mM | Human tumor cells |
Parameters with uncertainty
- Among different isoforms the MCT1 in Tumour cells are considered in this model. The is defined as and [2] with 6 experiments.
- In the legend of Table-1 of [3] it states that the Km and Vmax values for monocarboxylate transport are from mouse Ehrlich Lettre ́ tumor cells. We also consider these values for and . In the publication the values are given in with 7 experiments. Calculating Std. Dev. from S.E gives, for and for .
Parameter | Value | Units | Organism | Remarks |
---|---|---|---|---|
Human tumor cells | ||||
Human Tumor cell | ||||
mM | Human tumour cell | |||
mM | Human tumor cells |
Equilibrium constant
- The value of the transporters are reported to be 1.00.[4][5] As the is directly related to values of substrate and product, the uncertainty would also be dependent. The highest uncertainty is mentioned for which is of the actual value. The same percentage of error is assumed for ; .
Alternative-2: In order to ensure that the uncertainty does not affect the model equilibrium a small uncertainty of 5% can be considered. In our model we have applied this approach. So
References
- ↑ Halestrap AP, Meredith D (2004). The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch. 447 (5): 619–28 (doi)
- ↑ 2.0 2.1 2.2 Manning Fox JE et. al. (2000). Characterisation of human monocarboxylate transporter 4 substantiates its role in lactic acid efflux from skeletal muscle. J Physiol 529(Pt2):285-293
- ↑ 3.0 3.1 3.2 Jackson VN, Halestrap AP (1996) The kinetics, substrate, and inhibitor specificity of the monocarboxylate (lactate) transporter of rat liver cells determined using the fluorescent intracellular pH indicator, 2’,7’-bis(carboxyethyl)-5(6)-carboxyfluorescein. J Biol Chem 271:861–868
- ↑ Ettore Murabito (2011), Application of Differential Metabolic Control Analysis to Identify New Targets in Cancer Treatment, (PhD Thesis), University of Manchester
- ↑ 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