Publications

• Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis oocytes by changes in cytosolic pH.

  Broeer S., Schneider H.P., Broeer A., Rahman B., Hamprecht B., Deitmer J.W.

  Several laboratories have investigated monocarboxylate transport in a variety of cell types. The characterization of the cloned transporter isoforms in a suitable expression system is nevertheless still lacking. H+/monocarboxylate co-transport was therefore investigated in monocarboxylate transpor ... >> More

  Several laboratories have investigated monocarboxylate transport in a variety of cell types. The characterization of the cloned transporter isoforms in a suitable expression system is nevertheless still lacking. H+/monocarboxylate co-transport was therefore investigated in monocarboxylate transporter 1 (MCT1)-expressing Xenopus laevis oocytes by using pH-sensitive microelectrodes and [14C]lactate. Superfusion with lactate resulted in intracellular acidification of MCT1-expressing oocytes, but not in non-injected control oocytes. The basic kinetic properties of lactate transport in MCT1-expressing oocytes were determined by analysing the rates of intracellular pH changes under different conditions. The results were in agreement with the known properties of the transporter, with respect to both the dependence on the lactate concentration and the external pH value. Besides lactate, MCT1 mediated the reversible transport of a wide variety of monocarboxylic acids including pyruvate, D,L-3-hydroxybutyrate, acetoacetate, alpha-oxoisohexanoate and alpha-oxoisovalerate, but not of dicarboxylic and tricarboxylic acids. The inhibitor alpha-cyano-4-hydroxycinnamate bound strongly to the transporter without being translocated, but could be displaced by the addition of lactate. In addition to changes in the intracellular pH, lactate transport also induced deviations from the resting membrane potential. << Less

  Biochem. J. 333:167-174(1998) [PubMed] [EuropePMC]

  This publication is cited by 4 other entries.

• Participation of a proton-cotransporter, MCT1, in the intestinal transport of monocarboxylic acids.

  Tamai I., Takanaga H., Maeda H., Sai Y., Ogihara T., Higashida H., Tsuji A.

  A molecular mechanism for the intestinal monocarboxylic acid transport was characterized by using a proton/monocarboxylate transporter, MCT1, in Chinese hamster ovary (CHO) cells, first found by Garcia et al. (Cell, 76, 865-873, 1994). Northern blotting analysis showed that MCT1-isomers exist in t ... >> More

  A molecular mechanism for the intestinal monocarboxylic acid transport was characterized by using a proton/monocarboxylate transporter, MCT1, in Chinese hamster ovary (CHO) cells, first found by Garcia et al. (Cell, 76, 865-873, 1994). Northern blotting analysis showed that MCT1-isomers exist in the rat and rabbit intestinal enterocytes and Caco-2 cells. The expression of [14C]lactic acid uptake by Xenopus laevis oocytes injected with rabbit intestinal mRNA was reduced by hybridizing the mRNA with a MCT1 cDNA of CHO cells before microinjection used as the antisense DNA. [14C]Lactic acid uptake by CHO cells was pH dependent, saturable, stereospecific, and reduced in the presence of acetic acid, benzoic acid, S- and R-ibuprofen, S- and R-mandelic acid, nicotinic acid, pravastatin, propionic acid and valproic acid. In addition, several monocarboxylic acids were transported in pH-dependent and saturable manners. These results suggest that the intestinal MCT1-related protein contributes to a carrier-mediated absorption for organic weak acid compounds. << Less

  Biochem Biophys Res Commun 214:482-489(1995) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• Comparison of lactate transport in astroglial cells and monocarboxylate transporter 1 (MCT 1) expressing Xenopus laevis oocytes. Expression of two different monocarboxylate transporters in astroglial cells and neurons.

  Broeer S., Rahman B., Pellegri G., Pellerin L., Martin J.L., Verleysdonk S., Hamprecht B., Magistretti P.J.

  The transport of lactate is an essential part of the concept of metabolic coupling between neurons and glia. Lactate transport in primary cultures of astroglial cells was shown to be mediated by a single saturable transport system with a Km value for lactate of 7.7 mM and a Vmax value of 250 nmol/ ... >> More

  The transport of lactate is an essential part of the concept of metabolic coupling between neurons and glia. Lactate transport in primary cultures of astroglial cells was shown to be mediated by a single saturable transport system with a Km value for lactate of 7.7 mM and a Vmax value of 250 nmol/(min x mg of protein). Transport was inhibited by a variety of monocarboxylates and by compounds known to inhibit monocarboxylate transport in other cell types, such as alpha-cyano-4-hydroxycinnamate and p-chloromercurbenzenesulfonate. Using reverse transcriptase-polymerase chain reaction and Northern blotting, the presence of mRNA coding for the monocarboxylate transporter 1 (MCT1) was demonstrated in primary cultures of astroglial cells. In contrast, neuron-rich primary cultures were found to contain the mRNA coding for the monocarboxylate transporter 2 (MCT2). MCT1 was cloned and expressed in Xenopus laevis oocytes. Comparison of lactate transport in MCT1 expressing oocytes with lactate transport in glial cells revealed that MCT1 can account for all characteristics of lactate transport in glial cells. These data provide further molecular support for the existence of a lactate shuttle between astrocytes and neurons. << Less

  J. Biol. Chem. 272:30096-30102(1997) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes.

  Broeer S., Broeer A., Schneider H.P., Stegen C., Halestrap A.P., Deitmer J.W.

  Observations on lactate transport in brain cells and cardiac myocytes indicate the presence of a high-affinity monocarboxylate transporter. The rat monocarboxylate transporter isoform MCT2 was analysed by expression in Xenopus laevis oocytes and the results were compared with the known characteris ... >> More

  Observations on lactate transport in brain cells and cardiac myocytes indicate the presence of a high-affinity monocarboxylate transporter. The rat monocarboxylate transporter isoform MCT2 was analysed by expression in Xenopus laevis oocytes and the results were compared with the known characteristics of lactate transport in heart and brain. Monocarboxylate transport via MCT2 was driven by the H(+) gradient over the plasma membrane. Uptake of lactate strongly increased with decreasing pH, showing half-maximal stimulation at pH 7.2. A wide variety of monocarboxylates and ketone bodies, including lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, 2-oxoisovalerate and 2-oxoisohexanoate, were substrates of MCT2. All substrates had a high affinity for MCT2. For lactate a K(m) value of 0.74+/-0.07 mM was determined at pH 7.0. For the other substrates, K(i) values between 100 microM and 1 mM were measured for inhibition of lactate transport, which is about one-tenth of the corresponding values for the ubiquitously expressed monocarboxylate transporter isoform MCT1. Monocarboxylate transport via MCT2 could be inhibited by alpha-cyano-4-hydroxycinnamate, anion-channel inhibitors and flavonoids. It is suggested that cells which express MCT2 preferentially use lactate and ketone bodies as energy sources. << Less

  Biochem. J. 341:529-535(1999) [PubMed] [EuropePMC]

  This publication is cited by 6 other entries.

• Transport of L-lactate, D-lactate, and glycolate by the LldP and GlcA membrane carriers of Escherichia coli.

  Nunez M.F., Kwon O., Wilson T.H., Aguilar J., Baldoma L., Lin E.C.C.

  To examine the substrate specificity of the membrane transport carriers LldP (L-lactate permease) and GlcA (glycolate permease) of Escherichia coli, a mutant strain lacking their structural genes and blocked in the metabolism of the tested substrates was constructed and transformed with a plasmid ... >> More

  To examine the substrate specificity of the membrane transport carriers LldP (L-lactate permease) and GlcA (glycolate permease) of Escherichia coli, a mutant strain lacking their structural genes and blocked in the metabolism of the tested substrates was constructed and transformed with a plasmid bearing either the lldP or the glcA gene. Each transformant acquired the ability to accumulate L-lactate, D-lactate, and glycolate against a high concentration gradient. Substrate accumulation was inhibited by carbonyl cyanide m-chlorophenylhydrazone, a hydrophobic proton conductor that dissipates proton motive force. Competition of (14)C-L-lactate transport by nonradioactive L-lactate, D-lactate, and glycolate in LldP synthesizing cells and competition of (14)C-glycolate transport by the same three substrates in GlcA synthesizing cells showed that both carriers effectively transported all three substrates with a K(i) value ranging from 10 to 20 microM. D-Lactate does not appear to have a permease of its own. Utilization of the compound depends mainly on LldP. << Less

  Biochem. Biophys. Res. Commun. 290:824-829(2002) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• Identity of a Plasmodium lactate/H(+) symporter structurally unrelated to human transporters.

  Wu B., Rambow J., Bock S., Holm-Bertelsen J., Wiechert M., Soares A.B., Spielmann T., Beitz E.

  Maintenance of a high glycolytic flow rate is critical for the rapid growth and virulence of malarial parasites. The parasites release two moles of lactic acid per mole of glucose as the anaerobic end product. However, the molecular identity of the Plasmodium lactate transporter is unknown. Here w ... >> More

  Maintenance of a high glycolytic flow rate is critical for the rapid growth and virulence of malarial parasites. The parasites release two moles of lactic acid per mole of glucose as the anaerobic end product. However, the molecular identity of the Plasmodium lactate transporter is unknown. Here we show that a member of the microbial formate-nitrite transporter family, PfFNT, acts as a lactate/proton symporter in Plasmodium falciparum. Besides L-lactate, PfFNT transports physiologically relevant D-lactate, as well as pyruvate, acetate and formate, and is inhibited by the antiplasmodial compounds phloretin, furosemide and cinnamate derivatives, but not by p-chloromercuribenzene sulfonate (pCMBS). Our data on PfFNT monocarboxylate transport are consistent with those obtained with living parasites. Moreover, PfFNT is the only transporter of the plasmodial glycolytic pathway for which structure information is available from crystals of homologous proteins, rendering it amenable to further evaluation as a novel antimalarial drug target. << Less

  Nat. Commun. 6:6284-6284(2015) [PubMed] [EuropePMC]

  This publication is cited by 4 other entries.