Monocarboxylate transporter 1
| SLC16A1 | |||
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Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process |
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| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
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| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 1: 112.91 – 112.96 Mb | Chr 3: 104.55 – 104.57 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Monocarboxylate transporter 1 is a ubiquitous protein that in humans is encoded by the SLC16A1 gene (also known as MCT1).[5][6][7] 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.
MCT1 can be upregulated by PPAR-α, Nrf2, and AMPK.[8]
Animal studies
Overexpression of MCT1 has been shown to increase the efficacy of an anti-cancer drug currently undergoing clinical trials called
Clinical significance
Most cases of
Hyperinsulinemic hypoglycemia, familial, 7 (HHF7) is an autosomal dominant disease on the SLC16A1/MCT gene on chromosome 1p13.2. It causes hyperinsulinemic hypoglycemia, where hyperinsulinism is exercise-induced.[12]
Monocarboxylate transporter 1 deficiency (MCTD1) is an autosomal dominant and recessive disease on the SLC16A1/MCT1 gene on chromosome 1p13.2. It causes poor feeding and vomiting, intellectual disability, ketotic hypoglycemia, ketoacidosis, ketonuria, with episodes brought on by fasting or infection.[13]
Erythrocyte lactate transporter defect (formerly, myopathy due to lactate transport defect) is an autosomal dominant disease on the SLC16A1/MCT gene on chromosome 1p.13.2. It causes exercise-induced muscle cramping, stiffness, and fatigue (exercise intolerance); symptoms may also be induced by heat. Although symptoms present in the muscles, muscle biopsy and EMG are normal. Decreased erythrocyte (red blood cell) lactate clearance, decreased lactate clearance from muscle after exercise, and elevated serum creatine kinase.[14]
References
- ^ a b c ENSG00000281917 GRCh38: Ensembl release 89: ENSG00000155380, ENSG00000281917 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032902 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- S2CID 22137883.
- PMID 7835905.
- ^ "Entrez Gene: SLC16A1 solute carrier family 16, member 1 (monocarboxylic acid transporter 1)".
- PMID 32144120.
- PMID 26609475.
- PMID 11943706.
- PMID 22522610.
- ^ "HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 7; HHF7". omim.org. Retrieved 2023-08-21.
- ^ "MONOCARBOXYLATE TRANSPORTER 1 DEFICIENCY; MCT1D". omim.org. Retrieved 2023-08-21.
- ^ "ERYTHROCYTE LACTATE TRANSPORTER DEFECT". omim.org. Retrieved 2023-08-21.
Further reading
- Bonen A (Nov 2001). "The expression of lactate transporters (MCT1 and MCT4) in heart and muscle". European Journal of Applied Physiology. 86 (1): 6–11. S2CID 12166288.
- Halestrap AP, Meredith D (Feb 2004). "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. S2CID 15498611.
- Kim CM, Goldstein JL, Brown MS (Nov 1992). "cDNA cloning of MEV, a mutant protein that facilitates cellular uptake of mevalonate, and identification of the point mutation responsible for its gain of function". The Journal of Biological Chemistry. 267 (32): 23113–21. PMID 1429658.
- Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. PMID 8889548.
- Ritzhaupt A, Wood IS, Ellis A, Hosie KB, Shirazi-Beechey SP (Dec 1998). "Identification and characterization of a monocarboxylate transporter (MCT1) in pig and human colon: its potential to transport L-lactate as well as butyrate". The Journal of Physiology. 513 (Pt 3): 719–32. PMID 9824713.
- Rahman B, Schneider HP, Bröer A, Deitmer JW, Bröer S (Aug 1999). "Helix 8 and helix 10 are involved in substrate recognition in the rat monocarboxylate transporter MCT1". Biochemistry. 38 (35): 11577–84. PMID 10471310.
- Brooks GA, Brown MA, Butz CE, Sicurello JP, Dubouchaud H (Nov 1999). "Cardiac and skeletal muscle mitochondria have a monocarboxylate transporter MCT1". Journal of Applied Physiology. 87 (5): 1713–8. S2CID 1484319.
- Merezhinskaya N, Fishbein WN, Davis JI, Foellmer JW (Jan 2000). "Mutations in MCT1 cDNA in patients with symptomatic deficiency in lactate transport". Muscle & Nerve. 23 (1): 90–7. S2CID 36707820.
- Kirk P, Wilson MC, Heddle C, Brown MH, Barclay AN, Halestrap AP (Aug 2000). "CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression". The EMBO Journal. 19 (15): 3896–904. PMID 10921872.
- Cuff MA, Lambert DW, Shirazi-Beechey SP (Mar 2002). "Substrate-induced regulation of the human colonic monocarboxylate transporter, MCT1". The Journal of Physiology. 539 (Pt 2): 361–71. PMID 11882670.
- Cuff MA, Shirazi-Beechey SP (Apr 2002). "The human monocarboxylate transporter, MCT1: genomic organization and promoter analysis". Biochemical and Biophysical Research Communications. 292 (4): 1048–56. PMID 11944921.
- Lambert DW, Wood IS, Ellis A, Shirazi-Beechey SP (Apr 2002). "Molecular changes in the expression of human colonic nutrient transporters during the transition from normality to malignancy". British Journal of Cancer. 86 (8): 1262–9. PMID 11953883.
- Zhang GZ, Huang GJ, Li WL, Wu GM, Qian GS (Jul 2002). "[Effect of co-inhibition of MCT1 gene and NHE1 gene on proliferation and growth of human lung adenocarcinoma cells]". AI Zheng = Aizheng = Chinese Journal of Cancer. 21 (7): 719–23. PMID 12479094.
- Philp NJ, Wang D, Yoon H, Hjelmeland LM (Apr 2003). "Polarized expression of monocarboxylate transporters in human retinal pigment epithelium and ARPE-19 cells". Investigative Ophthalmology & Visual Science. 44 (4): 1716–21. PMID 12657613.
- Asada K, Miyamoto K, Fukutomi T, Tsuda H, Yagi Y, Wakazono K, Oishi S, Fukui H, Sugimura T, Ushijima T (2003). "Reduced expression of GNA11 and silencing of MCT1 in human breast cancers". Oncology. 64 (4): 380–8. S2CID 9041712.
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