Monocarboxylate transporter 1 is a ubiquitous
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''SLC16A1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
(also known as MCT1).
It is a proton coupled
monocarboxylate transporter The monocarboxylate transporters, or MCTs, are a family of proton-linked
plasma membrane transporters that carry molecules having one carboxylate group (monocarboxylates), such as lactate, pyruvate, and ketones across biological membranes. Acetat ...
.
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
Nuclear factor erythroid 2-related factor 2 (NRF2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the ''NFE2L2'' gene. NRF2 is a basic leucine zipper (bZIP) protein that may regu ...
, and
AMPK.
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.
Clinical significance
Most cases of
alveolar soft part sarcoma
Alveolar soft part sarcoma, abbreviated ASPS, is a very rare type of soft-tissue sarcoma, that grows slowly and whose cell of origin is unknown.
ASPS arises mainly in children and young adults and can migrate (metastasize) into other parts of the ...
show
PAS(+), diastase-resistant (
PAS-D (+)) intracytoplasmic crystals which contain
CD147
Basigin (BSG) also known as extracellular matrix metalloproteinase inducer (EMMPRIN) or cluster of differentiation 147 (CD147) is a protein that in humans is encoded by the ''BSG'' gene. This protein is a determinant for the Ok blood group syst ...
and monocarboxylate transporter 1 (MCT1).
Overexpression of MCT1 in
pancreatic
The pancreas (plural pancreases, or pancreata) is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine ...
beta cells
Beta cells (β-cells) are specialized endocrine cells located within the pancreatic islets of Langerhans responsible for the production and release of insulin and amylin. Constituting ~50–70% of cells in human islets, beta cells play a vit ...
leads to
hyperinsulinism
Hyperinsulinism refers to an above normal level of insulin in the blood of a person or animal. Normal insulin secretion and blood levels are closely related to the level of glucose in the blood, so that a given level of insulin can be normal for o ...
during
exercise
Exercise or workout is physical activity that enhances or maintains fitness and overall health. It is performed for various reasons, including weight loss or maintenance, to aid growth and improve strength, develop muscles and the cardio ...
.
, 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.
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.
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
Exercise intolerance is a condition of inability or decreased ability to perform physical exercise at the normally expected level or duration for people of that age, size, sex, and muscle mass. It also includes experiences of unusually severe pos ...
); 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
Creatine kinase (CK), also known as creatine phosphokinase (CPK) or phosphocreatine kinase, is an enzyme () expressed by various tissues and cell types. CK catalyses the conversion of creatine and uses adenosine triphosphate (ATP) to create phos ...
.
References
Further reading
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Solute carrier family
{{membrane-protein-stub
Inborn errors of carbohydrate metabolism