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Cited by 339

The DOI matches its Crossref record; 299 of the 299 references it cites were found in a registry or an index.

Monocarboxylic Acid Transport

Halestrap, Andrew P.·2013·Comprehensive Physiology
DOI 10.1002/cphy.c130008
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Abstract

Monocarboxylates such as lactate, pyruvate, and the ketone bodies play major roles in metabolism and must be transported across both the plasma membrane and mitochondrial inner membrane. A family of five proton-linked MonoCarboxylate Transporters (MCTs) is involved in the former and the mitochondrial pyruvate carrier (MPC) mediates the latter. In the intestine and kidney, two Sodium-coupled MonoCarboxylate Transporters (SMCTs) provide active transport of monocarboxylates across the apical membrane of the epithelial cells with MCTs on the basolateral membrane transporting the accumulated monocarboxylate into the blood. The kinetics and substrate and inhibitor specificities of MCTs, SMCTs, and the MPC have been well characterized and the molecular identity of the MCTs and SMCTs defined unequivocally. The identity of the MPC is less certain. The MCTs have been extensively studied and the three-dimensional structure of MCT1 has been modeled and a likely catalytic mechanism proposed. MCTs require the binding of a single transmembrane glycoprotein (either embigin or basigin) for activity. Regulation of MCT activity involves both transcriptional and posttranscriptional mechanisms, examples being upregulation of MCT1 by chronic exercise in red muscle (which oxidizes lactate) and in T-lymphocytes upon stimulation. MCT4 has properties that make it especially suited for lactic acid export by glycolytic cells and is upregulated by hypoxia. Some disease states are associated with modulation of plasma membrane and mitochondrial monocarboxylate transport and MCTs are promising drug targets for cancer chemotherapy. They may also be involved in drug uptake from the intestine and subsequent transport across the blood brain barrier.

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Metadata

Authors
Halestrap, A. P.
Venue
Comprehensive Physiology
Publisher
Wiley
Published
2013-10-22
Volume
3
Issue
4
Pages
1611-1643
ISSN
2040-4603 (ISSN-L)
DOI
10.1002/cphy.c130008
OpenAlex
W2164499983
Cited by
339
References
299
Type
other
Language
en
Open access
closed

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