The DOI matches its Crossref record; 299 of the 299 references it cites were found in a registry or an index.
Monocarboxylic Acid Transport
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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Cites
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Oligodendroglia metabolically support axons and contribute to neurodegeneration
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Cited by
Cancer metabolism: a therapeutic perspective
Martinez-Outschoorn, U. E., Peiris-Pagés, M., Pestell, R. G., Sotgia, F., & Lisanti, M. P. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.60 · Cited by 1,505
Lactate in the brain: from metabolic end-product to signalling molecule
Magistretti, P. J., & Allaman, I. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2018.19 · Cited by 1,298
A Cellular Perspective on Brain Energy Metabolism and Functional Imaging
Magistretti, P. J., & Allaman, I. (2015) · Neuron · doi:10.1016/j.neuron.2015.03.035 · Cited by 1,285
Metabolic Interactions in the Tumor Microenvironment
Lyssiotis, C. A., & Kimmelman, A. C. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.06.003 · Cited by 853
In vivo evidence for a lactate gradient from astrocytes to neurons
Mächler, P., Wyss, M. T., Elsayed, M., Stobart, J., Gutierrez, R., von Faber-Castell, A., Kaelin, V., Zuend, M., San Martín, A., Romero-Gómez, I., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.10.010 · Cited by 571
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)
- OpenAlex
- W2164499983
- Cited by
- 339
- References
- 299
- Type
- other
- Language
- en
- Open access
- closed
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