Difference between revisions of "Monocarboxylate (Lactate) transporter"
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* In the legend of Table-1 of <ref name="jackson_1996"></ref> it states that the Km and Vmax values for monocarboxylate transport are from mouse Ehrlich Lettre ́ tumor cells. We also consider these values for <math>Km_{Lactate_{out}}</math> and <math>V_{mr}</math>. In the publication the values are given in <math>mean \pm S.E.</math> with 7 experiments. Calculating Std. Dev. from S.E gives, <math>4.54 \pm 1.93</math> for <math>Km_{Lactate_{out}}</math> and <math>0.0207 \pm 0.003</math> for <math>V_{mr}</math>. | * In the legend of Table-1 of <ref name="jackson_1996"></ref> it states that the Km and Vmax values for monocarboxylate transport are from mouse Ehrlich Lettre ́ tumor cells. We also consider these values for <math>Km_{Lactate_{out}}</math> and <math>V_{mr}</math>. In the publication the values are given in <math>mean \pm S.E.</math> with 7 experiments. Calculating Std. Dev. from S.E gives, <math>4.54 \pm 1.93</math> for <math>Km_{Lactate_{out}}</math> and <math>0.0207 \pm 0.003</math> for <math>V_{mr}</math>. | ||
+ | |||
+ | * <ref name="Bröer_1998">Bröer, S., Schneider, H. P., Bröer, A., Rahman, B., Hamprecht, B., and Deitmer, J. W. (1998) Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis oocytes by changes in cytosolic pH. Biochem. J. 333, 167–174.</ref> reported that the value of <math>V_{mf}</math> is 100% of <math>Km_{Lactate_{in}}</math>. In that respect we considered this value in our model. | ||
{|class="wikitable" | {|class="wikitable" | ||
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|<math>V_{mf}</math> | |<math>V_{mf}</math> | ||
− | |<math>2.5 \pm 0.48</math> | + | |<math>2.5 \pm 0.48</math> <br> 100% of <math>Km_{Lactate_{in}}</math> |
| <math>\text{mM min}^{-1}</math> | | <math>\text{mM min}^{-1}</math> | ||
|Human tumor cells | |Human tumor cells |
Latest revision as of 12:12, 29 October 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
![Lactate_{in} \rightleftharpoons Lactate_{out}](/wiki/images/math/9/4/7/9473e479aa23c3e2aa5b6b08d60ad0d7.png)
Rate equation
Reversible Michaelis-Menten rate law is used
![\frac{V_{mf} \times \frac{[Lactate_{in}]}{Km_{Lactate_{in}}} - Vmr \times \frac{[Lactate_{out}]}{Km_{Lactate_{out}}}}{1 + \frac{[Lactate_{in}]}{Km_{Lactate_{in}}} + \frac{[Lactate_{out}]}{Km_{Lactate_{out}}}}](/wiki/images/math/9/7/f/97f35c7a18828761f166888b13a2c645.png)
Modified rate law to take Thermodynamic constraint into consideration
![\frac{V_{mf} \frac{[Lactate_{in}]}{Km_{Lactate_{in}}} \left(1 - \frac{[Lactate_{out}]}{K_{eq}[Lactate_{in}] } \right)}{1 + \frac{[Lactate_{in}]}{Km_{Lactate_{in}}} + \frac{[Lactate_{out}]}{Km_{Lactate_{out}}}}](/wiki/images/math/5/5/e/55ea56557248babfe67ad27eaf2220f9.png)
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
.
- [4] reported that the value of
is 100% of
. In that respect we considered this value in our model.
Parameter | Value | Units | Organism | Remarks |
---|---|---|---|---|
![]() |
![]() 100% of ![]() |
![]() |
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.[5][6] 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 for transporter. 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
- ↑ Bröer, S., Schneider, H. P., Bröer, A., Rahman, B., Hamprecht, B., and Deitmer, J. W. (1998) Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis oocytes by changes in cytosolic pH. Biochem. J. 333, 167–174.
- ↑ 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