Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes.
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.
Bröer
S
S
Physiologisch-chemisches Institut der Eberhard-Karls-Universität Tübingen, Hoppe-Seyler-Strasse 4, D-72076 Tübingen, Germany. stefan.broeer@uni-tuebingen.de
Bröer
A
A
Schneider
H P
HP
Stegen
C
C
Halestrap
A P
AP
Deitmer
J W
JW
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D017931:DNA Primers; D005260:Female; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters; D009865:Oocytes / Q000378:metabolism; D051381:Rats; D013379:Substrate Specificity; D014982:Xenopus laevis
D002352:Carrier Proteins; D017931:DNA Primers; D027501:Monocarboxylic Acid Transporters; C091633:Slc16a7 protein, rat; D019344:Lactic Acid