Transporters of monocarboxylates: characterizaiton and functional roles
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Apr 16, 2015
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Abstract
The rapid transport of monocarboxylates, such as lactate, pyruvate and β-hydroxybutyrate, across membranes is essential for maintaining cellular homeostasis. They are mainly transported by three well-characterized protein carrier families: SLC16/monocarboxylate transporters (MCTs), SLC5/sodium-coupled monocarboxylate transporters (SMCTs), and mitochondrial pyruvate carriers (MPCs). There are 14 members in the SLC16 family (MCT1-14), however, only 5 of them (MCT1-4 and MCT7) can transport monocarboxylates. This transport process is proton-linked, electroneutral and driven by a concentration gradient of their substrates. MCT1, MCT2 and MCT4 have a broad expression pattern in various tissues with affinities in the order of MCT2>MCT1>MCT4. They play important roles in local functions and malfunctions of MCTs have been associated with devastating disorders such as cancer, obesity and ischemia. Two members of the SLC5 family, SLC5A8 (SMCT1) and SLC5A12 (SMCT2), transport monocarboxylates in a Na+-dependent, electrogenic manner with a stoichiometry being 2:1 for Na+/substrate. They play particularly important roles in short-chain fatty acids uptake in large intestine and regulation of uric acid reabsorption in kidney. MPCs (MPC1-2) form a large heterocomplex at the inner membrane of mitochondria and are mainly responsible for pyruvate transport into mitochondrial matrix to fuel Krebs cycle. Genetic mutations within these monocarboxylates carrier genes have been identified as causal factors for many diseases. Thus, a better understanding of their functions and regulations will help advance novel therapeutic interventions under certain pathological conditions.
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LIU, Zejian; WANG, Meina.
Transporters of monocarboxylates: characterizaiton and functional roles.
Medical Research Archives, [S.l.], n. 2, apr. 2015.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/68>. Date accessed: 20 apr. 2024.
Keywords
monocarboxylate transporter (MCT); sodium-coupled monocarboxylate transporter (SMCT); mitochondrial pyruvate carrier (MPC); lactate; pyruvate; metabolism; drug transport; cancer; diabetes
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Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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