Monocarboxylate transporter 1

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External IDsGeneCards: [1]
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SpeciesHumanMouse
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Monocarboxylate transporter 1 is a protein that in humans is encoded by the SLC16A1 gene (also known as MCT1).[1][2][3] It is a proton coupled monocarboxylate transporter.

Biochemistry

Detailed kinetic analysis of monocarboxylate transport in erythrocytes revealed that MCT1 operates through an ordered mechanism. MCT1 has a substrate binding site open to the extracellular matrix which binds a proton first followed by the lactate anion. The protein then undergoes a conformational change to a new ‘closed’’ conformation that exposes both the proton and lactate to the opposite surface of the membrane where they are released, lactate first and then the proton. For net transport of lactic acid, the rate-limiting step is the return of MCT1 without bound substrate to the open conformation. For this reason, exchange of one monocarboxylate inside the cell with another outside is considerably faster than net transport of a monocarboxylate across the membrane.

Animal studies

Overexpression of MCT1 has been shown to increase the efficacy of an anti-cancer drug currently undergoing clinical trials called 3-bromopyruvate in breast cancer cells.[4]

Clinical significance

Most cases of alveolar soft part sarcoma show PAS(+), diastase-resistant (PAS-D (+)) intracytoplasmic crystals which contain CD147 and monocarboxylate transporter 1 (MCT1).[5] Overexpression of MCT1 in pancreatic beta cells leads to hyperinsulinism during exercise.[6]

See also

References

  1. Garcia CK, Goldstein JL, Pathak RK, Anderson RG, Brown MS (Mar 1994). "Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle". Cell. 76 (5): 865–73. doi:10.1016/0092-8674(94)90361-1. PMID 8124722.
  2. Garcia CK, Li X, Luna J, Francke U (Sep 1994). "cDNA cloning of the human monocarboxylate transporter 1 and chromosomal localization of the SLC16A1 locus to 1p13.2-p12". Genomics. 23 (2): 500–3. doi:10.1006/geno.1994.1532. PMID 7835905.
  3. "Entrez Gene: SLC16A1 solute carrier family 16, member 1 (monocarboxylic acid transporter 1)".
  4. Liu Z, Sun Y, Hong H, Zhao S, Zou X, Ma R, Jiang C, Wang Z, Li H, Liu H (2015-08-15). "3-bromopyruvate enhanced daunorubicin-induced cytotoxicity involved in monocarboxylate transporter 1 in breast cancer cells". American Journal of Cancer Research. 5 (9): 2673–85. PMC 4633897. PMID 26609475.
  5. Ladanyi M, Antonescu CR, Drobnjak M, Baren A, Lui MY, Golde DW, Cordon-Cardo C (Apr 2002). "The precrystalline cytoplasmic granules of alveolar soft part sarcoma contain monocarboxylate transporter 1 and CD147". The American Journal of Pathology. 160 (4): 1215–21. doi:10.1016/S0002-9440(10)62548-5. PMC 1867200. PMID 11943706.
  6. Pullen TJ, Sylow L, Sun G, Halestrap AP, Richter EA, Rutter GA (Jul 2012). "Overexpression of monocarboxylate transporter-1 (SLC16A1) in mouse pancreatic β-cells leads to relative hyperinsulinism during exercise". Diabetes. 61 (7): 1719–25. doi:10.2337/db11-1531. PMC 3379650. PMID 22522610.

Further reading



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