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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. Acetate is actively transported to intestinal enteroendocrine cells via MCT, termed Targ (short for Tarag in Mongolian). 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 dehydrogen ...
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Proton
A proton is a stable subatomic particle, symbol , Hydron (chemistry), H+, or 1H+ with a positive electric charge of +1 ''e'' (elementary charge). Its mass is slightly less than the mass of a neutron and approximately times the mass of an electron (the proton-to-electron mass ratio). Protons and neutrons, each with a mass of approximately one Dalton (unit), dalton, are jointly referred to as ''nucleons'' (particles present in atomic nuclei). One or more protons are present in the Atomic nucleus, 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 chemical element, element is identified by the number of protons in its nucleus, each element has its own atomic number, which determines the number of atomic electrons and consequently the chemical characteristi ...
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AMP-activated Protein Kinase
5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme (EC 2.7.11.31) that plays a role in cellular energy homeostasis, largely to activate glucose and fatty acid uptake and oxidation when cellular energy is low. It belongs to a highly conserved eukaryotic protein family and its orthologues are SNF1 in yeast, and SnRK1 in plants. It consists of three proteins ( subunits) that together make a functional enzyme, conserved from yeast to humans. It is expressed in a number of tissues, including the liver, brain, and skeletal muscle. In response to binding AMP and ADP, the net effect of AMPK activation is stimulation of hepatic fatty acid oxidation, ketogenesis, stimulation of skeletal muscle fatty acid oxidation and glucose uptake, inhibition of cholesterol synthesis, lipogenesis, and triglyceride synthesis, inhibition of adipocyte lipogenesis, inhibition of adipocyte lipolysis, and modulation of insulin secretion by pancreat ...
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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, alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene may be included .... 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. See also * Solute carrier family The solute carrier (SLC) group of membrane transport proteins include over 400 members organized into 66 families. Most members of the SLC group are located in the cell membrane. The SLC gene nomenclature system was originally proposed by the HUGO ... 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 ...
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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 pa ...
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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 upregulated by ...
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Warburg Effect (oncology)
In oncology, the Warburg effect () is the observation that most cancers use aerobic glycolysis and lactic acid fermentation for energy generation rather than the mechanisms used by non-cancerous cells. 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 existence of the Warburg effect has fuelled popular misconceptions that cancer can be treated by dietary reductions in sugar and carbohydrate. 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 compared to the citric acid cycle and oxidative phosphorylation of aerobic respiration, it allows proliferating cells to convert nutrients such as glucose and glutamine more efficiently into biomass by avoiding unnecessary ...
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Oxygen Debt
Excess post-exercise oxygen consumption (EPOC, informally called afterburn) is a measurably increased rate of oxygen intake following strenuous activity. In historical contexts the term "oxygen debt" was popularized to explain or perhaps attempt to quantify anaerobic energy expenditure, particularly as regards lactic acid/ lactate metabolism; in fact, the term "oxygen debt" is still widely used to this day. However, direct and indirect calorimeter experiments have definitively disproven any association of lactate metabolism as causal to an elevated oxygen uptake. In recovery, oxygen (EPOC) is used in the processes that restore the body to a resting state and adapt it to the exercise just performed. These include: hormone balancing, replenishment of fuel stores, cellular repair, innervation, and anabolism. Post-exercise oxygen consumption replenishes the phosphagen system. New ATP is synthesized and some of this ATP donates phosphate groups to creatine until ATP and creatine le ...
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Cori Cycle
The Cori cycle (also known as the lactic acid cycle), named after its discoverers, Carl Ferdinand Cori and Gerty Cori, is a metabolic pathway in which lactic acid, lactate, produced by anaerobic glycolysis in muscles, is transported to the liver and converted to glucose, which then returns to the muscles and is cyclically metabolized back to lactate. Process Muscular activity requires Adenosine triphosphate, ATP, which is provided by the breakdown of glycogen in the skeletal muscles. The breakdown of glycogen, known as glycogenolysis, releases glucose in the form of glucose-1-phosphate, glucose 1-phosphate (G1P). The G1P is converted to G6P by phosphoglucomutase. G6P is readily fed into glycolysis, (or can go into the pentose phosphate pathway if G6P concentration is high) a process that provides ATP to the muscle cells as an energy source. During muscular activity, the store of ATP needs to be constantly replenished. When the supply of dioxygen, oxygen is sufficient, this energy ...
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Pyruvate
Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell. Pyruvic acid can be made from glucose through glycolysis, converted back to carbohydrates (such as glucose) via gluconeogenesis, or converted to fatty acids through a reaction with acetyl-CoA. It can also be used to construct the amino acid alanine and can be converted into ethanol or lactic acid via fermentation. Pyruvic acid supplies energy to cells through the citric acid cycle (also known as the Krebs cycle) when oxygen is present ( aerobic respiration), and alternatively ferments to produce lactate when oxygen is lacking. Chemistry In 1834, Théophile-Jules Pelouze distilled tartaric acid and isolated glutaric acid and another unknown organic acid. Jöns Jacob Berzelius characterized this other acid the following year and na ...
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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 pyruvic acid, pyruvate to lactic acid, lactate 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 lactic acid, lactate with concomitant interconversion of NADH and Nicotinamide adenine dinucleotide, NAD+. It converts pyruvate, the final produ ...
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