Monocarboxylate transporter 4 explained

Monocarboxylate transporter 4 (MCT4) also known as solute carrier family 16 member 3 is a protein that in humans is encoded by the SLC16A3 gene.^{[1] [2]}

Northern and western blotting and EST database analyses showed MCT4 to be widely expressed and especially so in glycolytic tissues such as white skeletal muscle fibers, astrocytes, white blood cells, chondrocytes, and some mammalian cell lines. Because of this, it has been proposed that the properties of MCT4 might be especially appropriate for export of lactate derived from glycolysis. MCT4 exhibits a lower affinity for most substrates and inhibitors than MCT1, with Km and Ki values some 5–10-fold higher. The high Km for pyruvate may be especially significant as this avoids loss of pyruvate from the cell which, were it to occur, would prevent removal of the reduced form of nicotinamide adenine dinucleotide (NADH) produced in glycolysis by reduction of pyruvate to lactate.

MCT4 can be upregulated by HIF-1α and AMPK.^[3]

See also

• Monocarboxylate transporter
• Solute carrier family

Further reading

• Halestrap AP, Price NT . The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation . The Biochemical Journal . 343 . 2 . 281–99 . Oct 1999 . 10510291 . 1220552 . 10.1042/0264-6021:3430281 .
• Halestrap AP, Meredith D . The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond . Pflügers Archiv: European Journal of Physiology . 447 . 5 . 619–28 . Feb 2004 . 12739169 . 10.1007/s00424-003-1067-2 . 15498611 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Kirk P, Wilson MC, Heddle C, Brown MH, Barclay AN, Halestrap AP . CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression . The EMBO Journal . 19 . 15 . 3896–904 . Aug 2000 . 10921872 . 306613 . 10.1093/emboj/19.15.3896 .
• Philp NJ, Wang D, Yoon H, Hjelmeland LM . Polarized expression of monocarboxylate transporters in human retinal pigment epithelium and ARPE-19 cells . Investigative Ophthalmology & Visual Science . 44 . 4 . 1716–21 . Apr 2003 . 12657613 . 10.1167/iovs.02-0287 .
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks . Cell . 127 . 3 . 635–48 . Nov 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . free .
• Wang Q, Morris ME . The role of monocarboxylate transporter 2 and 4 in the transport of gamma-Hydroxybutyric acid in mammalian cells . Drug Metabolism and Disposition . 35 . 8 . 1393–9 . Aug 2007 . 17502341 . 10.1124/dmd.107.014852 . 11072905 .

Notes and References

1. Price NT, Jackson VN, Halestrap AP . Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past . The Biochemical Journal . 329 . 2 . 321–8 . Jan 1998 . 9425115 . 1219047 . 10.1042/bj3290321.
2. Web site: Entrez Gene: SLC16A3 solute carrier family 16, member 3 (monocarboxylic acid transporter 4).
3. Felmlee MA, Jones RS, Morris ME . Monocarboxylate Transporters (SLC16): Function, Regulation, and Role in Health and Disease . . 72 . 2 . 466–485 . 2020 . 10.1124/pr.119.018762 . 7062045 . 32144120.