Transport of lactate and other monocarboxylates in mammalian cells is mediated by a family of transporters, designated monocarboxylate transporters (MCTs). The MCT4 member of this family has recently been identified as the major isoform of white muscle cells, mediating lactate efflux out of glycolytically active myocytes [Wilson, Jackson, Heddle, Price, Pilegaard, Juel, Bonen, Montgomery, Hutter and Halestrap (1998) J. Biol. Chem. 273, 15920–15926]. To analyse the functional properties of this transporter, rat MCT4 was expressed in Xenopus laevis oocytes and transport activity was monitored by flux measurements with radioactive tracers and by changes of the cytosolic pH using pH-sensitive microelectrodes. Similar to other members of this family, monocarboxylate transport via MCT4 is accompanied by the transport of H+ across the plasma membrane. Uptake of lactate strongly increased with decreasing extracellular pH, which resulted from a concomitant drop in the Km value. MCT4 could be distinguished from the other isoforms mainly in two respects. First, MCT4 is a low-affinity MCT: for l-lactate Km values of 17±3mM (pH-electrode) and 34±5mM (flux measurements with l-[U-14C]lactate) were determined. Secondly, lactate is the preferred substrate of MCT4. Km values of other monocarboxylates were either similar to the Km value for lactate (pyruvate, 2-oxoisohexanoate, 2-oxoisopentanoate, acetoacetate) or displayed much lower affinity for the transporter (β-hydroxybutyrate and short-chain fatty acids). Under physiological conditions, rat MCT will therefore preferentially transport lactate. Monocarboxylate transport via MCT4 could be competitively inhibited by α-cyano-4-hydroxycinnamate, phloretin and partly by 4,4´-di-isothiocyanostilbene-2,2´-disulphonic acid. Similar to MCT1, monocarboxylate transport via MCT4 was sensitive to inhibition by the thiol reagent p-chloromercuribenzoesulphonic acid.
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August 2000
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Research Article|
August 09 2000
The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells
Kai-Stefan DIMMER;
Kai-Stefan DIMMER
*Physiologisches Institut der Universität, Gmelinstr. 5, D-72076 Tübingen, Germany
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Björn FRIEDRICH;
Björn FRIEDRICH
*Physiologisches Institut der Universität, Gmelinstr. 5, D-72076 Tübingen, Germany
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Florian LANG;
Florian LANG
*Physiologisches Institut der Universität, Gmelinstr. 5, D-72076 Tübingen, Germany
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Joachim W. DEITMER;
Joachim W. DEITMER
†Abteilung für Allgemeine Zoologie, FB Biologie, Universität Kaiserslautern, Postfach 3049, D-67653 Kaiserslautern, Germany
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Stefan BRÖER
Stefan BRÖER
1
*Physiologisches Institut der Universität, Gmelinstr. 5, D-72076 Tübingen, Germany
‡Division of Biochemistry and Molecular Biology, Faculty of Science, Australian National University, Canberra ACT0200, Australia
1To whom correspondence should be addressed at the Physiologisches Institut der Universität (e-mail stefan.broeer@uni-tuebingen.de).
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Biochem J (2000) 350 (1): 219–227.
Article history
Received:
February 04 2000
Revision Received:
May 26 2000
Accepted:
June 08 2000
Citation
Kai-Stefan DIMMER, Björn FRIEDRICH, Florian LANG, Joachim W. DEITMER, Stefan BRÖER; The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells. Biochem J 15 August 2000; 350 (1): 219–227. doi: https://doi.org/10.1042/bj3500219
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