![]() Only 4 members of this transporter family (MCT1-4) have been identified as proton dependent MCTs which catalyze the transport of important monocarboxylates such as lactate, pyruvate, and ketone bodies. Proton dependent monocarboxylate transporters (MCTs SLC16A) are a family of transport proteins that contain 14 members which were identified based on sequence homology. Monocarboxylate transporters facilitate the transport of lactate and other monocarboxylates and therefore play an important role in cellular metabolism. In addition, some of the tissues such as brain, heart and red skeletal muscle utilize lactate as a fuel for respiration, thus requiring its import into the cell. This pathway leads to intracellular accumulation of lactate which must be exported out as high levels of lactate result in inhibition of glycolysis. ![]() Among these monocarboxylates, lactate which is the end product of glycolysis is particularly important. Monocarboxylic acids play an important role in energy metabolism in various tissues such as skeletal muscle, heart, brain and red blood cells. This review will also focus on utilization of MCTs as potential targets for drug delivery into the brain including their role in the treatment of malignant brain tumors. The physiological role of these transporters in the brain and their specific cellular localization within the brain will also be discussed. The influence of MCTs on drug pharmacokinetics has been extensively studied for γ-hydroxybutyrate (GHB) including distribution of this drug of abuse into the brain and the results will be summarized in this review. Apart from endogenous short chain monocarboxylates, they also mediate the transport of exogenous drugs such as salicylic acid, valproic acid, and simvastatin acid. Due to the expression of these transporters in the kidney, intestine, and brain, they may play an important role in influencing drug disposition. ![]() The various isoforms differ in terms of their substrate specificity and tissue localization. MCT1 is the predominant transporter among the MCT isoforms and is present in almost all tissues including kidney, intestine, liver, heart, skeletal muscle and brain. These act as a symporter and are dependent on a sodium gradient for their functional activity. Another transporter family involved in the transport of endogenous monocarboxylates is the sodium coupled MCTs (SMCTs). Currently, fourteen members of this transporter family have been identified by sequence homology, of which only the first four members (MCT1- MCT4) have been shown to mediate the proton-linked transport of monocarboxylates. ![]() Monocarboxylate transporters (MCTs) are known to mediate the transport of short chain monocarboxylates such as lactate, pyruvate and butyrate. ![]()
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