Monocarboxylate Transporters

There are 14 members of the solute carrier 16 (SLC16) gene family, four of which (SLC16A1, SLC16A3, SLC16A7 and SLC16A8) encode monocarboxylate transporters; MCT1, MCT4*, MCT2 and MCT3* respectively. MCTs have been shown to transport short-chain monocarboxylates such as L-lactate, ketone bodies and pyruvate across the plasma membrane of mammalian cells. MCTs have 12 transmembrane domains (TMDs) which consist of an intracellular N- and C-terminal and a large intracellular loop between TMDs 6 and 7. MCT1-4 require an ancillary protein either basigin or embigin, in order to express a fully functional protein at the plasma membrane.

MCTs are fundamental in the regulation of many processes including pH, respiration, glycolysis and gluconeogenesis. MCT1 is expressed in most tissues and facilitates lactic acid uptake for oxidation in cardiac and red skeletal muscle. MCT2 is a high affinity transporter; its expression is more limited than MCT1 and varies between species. MCT3 expression is confined to the basal membrane of the retinal pigment epithelium and choroid plexus epithelia. MCT4 is a low affinity transporter and is mainly expressed in highly glycolytic cells, such as white muscle fibers. Many cells can up regulate MCT4 expression under hypoxic conditions; this is mediated through transcriptional control by HIF-1α.

MCTs play a major role in the maintenance of the glycolytic metabolism through transport of lactate. MCT inhibitors have been shown to decrease glycolytic metabolism, migration and invasion, affect proliferation and induce cell death in certain cell lines. They are also useful tools for studying the Warburg effect.

*Note: MCT3 has the synonym MCT4 and MCT4 has the synonym MCT5; for further details please view Genecards.

External sources of pharmacological information for Monocarboxylate Transporters :

• IUPHAR Receptor Code

• BJP Guide

Literature for Monocarboxylate Transporters

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Cancer Metabolism Poster

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Monocarboxylate transporters Gene Data