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Overview
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Background
Monocarboxylates, such as lactate and pyruvate, play an integral role in cellular metabolism. Lactic acid is produced in large quantities as a result of glycolysis, which provides the majority of ATP to cells under normal physiological conditions. However, accumulation of lactic acid leads to a decrease in intracellular pH and cessation of glycolysis. In order for glycolysis to continue at a high rate, lactic acid must be transported out of the cell. This transport process is carried out by a family of monocarboxylate transporters (MCTs), which function as proton symports and are stereoselective for L-lactate. The MCT family consists of at least eight members, MCT1-8, which contain between 10-12 transmembrane-helical (TM) domains, with the amino and carboxy termini located in the cytoplasm. MCT6 is highly expressed in the kidneys and is thought to have a specificity for bumetanide, a loop diuretic involved in the treatment of edema. The high substrate specificity of MCT6 suggests a possible role in therapeutic drug transport and trafficking across the plasma membrane.
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