Difference between revisions of "Monocarboxylate (Lactate) transporter"

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(Parameters with uncertainty)
(Rate equation)
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Reversible Michaelis-Menten rate law is used
 
Reversible Michaelis-Menten rate law is used
  
<center><math> \frac{Vmf \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}}}} </math></center>
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<center><math> \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}}}} </math></center>
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Modified rate law to take Thermodynamic constraint into consideration
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<center><math> \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}}}} </math></center>
  
 
==Parameter values==
 
==Parameter values==

Revision as of 11:34, 20 June 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.

Chemical equation

 Lactate_{in} \rightleftharpoons Lactate_{out}

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}}}}

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}}}}

Parameter values

Parameter Value Units Organism Remarks
V_{mf} 2.5 [2] \text{mM min}^{-1} Human tumor cells
V_{mr} 2.4 [3] \text{mM min}^{-1} Rat liver cells
Km_{Lactate_{in}} 4.5 [3] mM Rat liver cell
Km_{Lactate_{out}} 4.54 [2] mM Human tumor cells

Parameters with uncertainty

  • Among different isoforms the MCT1 in Tumour cells are considered in this model. The Km_{Lactate_{in}} is defined as 4.38 \pm 1.81 and V_{mf} = 2.5 \pm 0.48 [2] with 6 experiments.
  • In the legend of Table-1 of [3] it states Km and Vmax values for monocarboxylate transport into mouse Ehrlich Lettre ́ tumor cells were taken in to consideration. Therefore we consider these values to be for Km_{Lactate_{out}} and V_{mr}. Here the values are given in mean \pm S.E. with 7 experiments. Calculating Std. Dev. from S.E gives, 4.54 \pm 1.93 for Km_{Lactate_{out}} and 0.0207 \pm 0.003 for V_{mr}.
Parameter Value Units Organism Remarks
V_{mf} 2.5 \pm 0.48 \text{mM min}^{-1} Human tumor cells
V_{mr} 0.0207 \pm 0.003 \text{mM min}^{-1} Human Tumor cell
Km_{Lactate_{in}} 4.38 \pm 1.81 mM Human tumour cell
Km_{Lactate_{out}} 4.54 \pm 1.93 mM Human tumor cells

References

  1. 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. 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. 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