Monocarboxylate transporter 1

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.

SLC16A1
Identifiers
Aliases	SLC16A1, HHF7, MCT, MCT1, MCT1D, solute carrier family 16 member 1
External IDs	OMIM: 600682; MGI: 106013; HomoloGene: 20662; GeneCards: SLC16A1; OMA:SLC16A1 - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p13.2 Start 112,911,847 bp[1] End 112,957,593 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3|3 F2.2 Start 104,545,984 bp[2] End 104,565,778 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of transverse colon ventricular zone smooth muscle tissue left ventricle endometrium rectum placenta duodenum skeletal muscle tissue right auricle Top expressed in retinal pigment epithelium optic nerve primitive streak left colon atrioventricular valve fetal liver hematopoietic progenitor cell atrium right ventricle mucous cell of stomach intercostal muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein homodimerization activity monocarboxylic acid transmembrane transporter activity mevalonate transmembrane transporter activity organic cyclic compound binding symporter activity lactate transmembrane transporter activity Cellular component integral component of membrane centrosome membrane plasma membrane integral component of plasma membrane mitochondrion extracellular exosome cell junction intracellular membrane-bounded organelle synapse Biological process monocarboxylic acid transport glucose homeostasis regulation of insulin secretion lipid metabolism behavioral response to nutrient cellular response to organic cyclic compound lactate transmembrane transport pyruvate metabolic process response to food mevalonate transport leukocyte migration transmembrane transport plasma membrane lactate transport centrosome cycle transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6566 20501 Ensembl ENSG00000155380 ENSG00000281917 ENSMUSG00000032902 UniProt P53985 Q5T8R3 P53986 RefSeq (mRNA) NM_001166496 NM_003051 NM_009196 RefSeq (protein) NP_001159968 NP_003042 NP_033222 Location (UCSC) Chr 1: 112.91 – 112.96 Mb Chr 3: 104.55 – 104.57 Mb PubMed search [3] [4]
Wikidata
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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.^{[citation needed]}

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 3-bromopyruvate in breast cancer cells.^[9]

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).^[10] Overexpression of MCT1 in pancreatic beta cells leads to hyperinsulinism during exercise.^[11]

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]