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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. MCTs are expressed in nearly every kind of cell. There are 14 MCTs corresponding to 14 solute carrier 16A transporters, although the cardinal numbers do not match (for example MCT3 is SLC16A8). MCTs 1-4 have been more carefully investigated than MCTs 5-14. MCTs can be upregulated by PPAR-α, HIF-1α, Nrf2, and AMPK. Lactate and the Cori cycle Lactate has long been considered a byproduct resulting from glucose breakdown through glycolysis during anaerobic metabolism. Glycolysis requires the coenzyme NAD+, and reduces it to NADH. As a means of regenerating NAD+ to allow glycolysis to continue, lactate dehydrogenase catalyzes the conversion of pyruvate to lactate in the cytosol, oxidizing NADH to NAD+. Lactate is then transported fr ...
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Proton
A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' elementary charge. Its mass is slightly less than that of a neutron and 1,836 times the mass of an electron (the proton–electron mass ratio). Protons and neutrons, each with masses of approximately one atomic mass unit, are jointly referred to as "nucleons" (particles present in atomic nuclei). One or more protons are present in the nucleus of every atom. They provide the attractive electrostatic central force which binds the atomic electrons. The number of protons in the nucleus is the defining property of an element, and is referred to as the atomic number (represented by the symbol ''Z''). Since each element has a unique number of protons, each element has its own unique atomic number, which determines the number of atomic electrons and consequently the chemical characteristics of the element. The word ''proton'' is Greek for "first", and this name was given to the ...
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Lactate Dehydrogenase
Lactate dehydrogenase (LDH or LD) is an enzyme found in nearly all living cells. LDH catalyzes the conversion of lactate to pyruvate and back, as it converts NAD+ to NADH and back. A dehydrogenase is an enzyme that transfers a hydride from one molecule to another. LDH exists in four distinct enzyme classes. This article is specifically about the NAD(P)-dependent L-lactate dehydrogenase. Other LDHs act on D-lactate and/or are dependent on cytochrome c: D-lactate dehydrogenase (cytochrome) and L-lactate dehydrogenase (cytochrome). LDH is expressed extensively in body tissues, such as blood cells and heart muscle. Because it is released during tissue damage, it is a marker of common injuries and disease such as heart failure. Reaction Lactate dehydrogenase catalyzes the interconversion of pyruvate and lactate with concomitant interconversion of NADH and NAD+. It converts pyruvate, the final product of glycolysis, to lactate when oxygen is absent or in short supp ...
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SLC16A9
Monocarboxylate transporter 9 (MCT9, solute carrier family 16, member 9, SLC16A9) is a protein that in humans is encoded by the ''SLC16A9'' gene. Clinical relevance Mutations in the SLC16A9 gene have been associated with carnitine Carnitine is a quaternary ammonium compound involved in metabolism in most mammals, plants, and some bacteria. In support of energy metabolism, carnitine transports long-chain fatty acids into mitochondria to be oxidized for energy production, an ... levels in blood. References Further reading * * * * * * * * Human proteins Solute carrier family {{membrane-protein-stub ...
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SLC16A8
Monocarboxylate transporter 3 (MCT3) also known as solute carrier family 16 member 8 is a protein that in humans is encoded by the ''SLC16A8'' gene. MCT is a proton-coupled monocarboxylate transporter. It catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate. It also functions as high-affinity pyruvate transporter. Expression of SLC16A8 is confined to the retinal pigment epithelium and choroid plexus epithelia, where it is located on the basal membrane in contrast to MCT1 which is found on the apical membrane. See also * 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. ...
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SLC16A7
Monocarboxylate transporter 2 (MCT2) also known as solute carrier family 16 member 7 (SLC16A7) is a protein that in humans is encoded by the ''SLC16A7'' gene. MCT2 is a proton-coupled monocarboxylate transporter. It catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactic acid, branched-chain oxo acids derived from leucine, valine, and isoleucine">valine.html" ;"title="leucine, valine">leucine, valine, and isoleucine, and the ketone bodies acetoacetate and beta-hydroxybutyrate. It also functions as high-Affinity (pharmacology), affinity pyruvate transporter. Both Northern blot analysis and inspection of the human expressed sequence tag (EST) database suggest relatively little expression of MCT2 in human tissues. As well, the sequence of MCT2 is far less conserved across species than that of MCT1 or MCT4 and there also appear to be considerable species differences in the tissue expression profile of this isoform. Of the four known mammali ...
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SLC16A5
Monocarboxylate transporter 6 (MCT6) is a protein in humans that is encoded by the SLC16A5 gene. This gene encodes a member of the monocarboxylate transporter family and the major facilitator superfamily. The encoded protein is localized to the cell membrane and acts as a proton-linked transporter of bumetanide. Transport by the encoded protein is inhibited by four loop diuretics, nateglinide, thiazides, probenecid, and glibenclamide. Alternative splicing results in multiple transcript variants Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be in .... rovided by RefSeq, Nov 2012 References Genes on human chromosome 17 Solute carrier family {{gene-17-stub ...
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SLC16A4
Monocarboxylate transporter 5 is a protein that in humans is encoded by the ''SLC16A4'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba .... See also * Solute carrier family References Further reading * * * * * * * * * * * * * * Solute carrier family {{membrane-protein-stub ...
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SLC16A3
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. 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. See also *M ...
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SLC16A2
Monocarboxylate transporter 8 (MCT8) is an active transporter protein that in humans is encoded by the ''SLC16A2'' gene. Function MCT8 actively transports a variety of iodo- thyronines including the thyroid hormones T3 and T4. Clinical significance A genetic disorder (discovered in 2003 and 2004) is caused by mutation in the transporter of thyroid hormone, MCT8, also known as SLC16A2, is believed to be account for a significant fraction of the undiagnosed neurological disorders (usually resulting in hypotonic/floppy infants with delayed milestones). This genetic defect was known as Allan–Herndon–Dudley syndrome (since 1944) without knowing its actual cause. It has been shown mutated in cases of X-linked leukoencephalopathy. Some of the symptoms for this disorder as are follows: normal to slightly elevated TSH, elevated T3 and reduced T4 (ratio of T3/T4 is about double its normal value). Normal looking at birth and for the first few years, hypotonic (floppy), in partic ...
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SLC16A1
Monocarboxylate transporter 1 is a ubiquitous protein that in humans is encoded by the ''SLC16A1'' gene (also known as MCT1). 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 upregulate ...
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Warburg Effect (oncology)
In oncology, the Warburg effect () is the observation that most cancer cells produce energy predominantly not through the 'usual' citric acid cycle and oxidative phosphorylation in the mitochondria as observed in normal cells, but through a less efficient process of 'aerobic glycolysis' consisting of high level of glucose uptake and glycolysis followed by lactic acid fermentation taking place in the cytosol, not the mitochondria, even in the presence of abundant oxygen. This observation was first published by Otto Heinrich Warburg, who was awarded the 1931 Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme". The precise mechanism and therapeutic implications of the Warburg effect, however, remain unclear. In fermentation, the last product of glycolysis, pyruvate, is converted into lactate (lactic acid fermentation) or ethanol (alcoholic fermentation). While fermentation produces adenosine triphosphate (ATP) only in low yield co ...
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