Malate-aspartate Shuttle
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Malate-aspartate Shuttle
The malate-aspartate shuttle (sometimes simply the malate shuttle) is a biochemical system for translocating electrons produced during glycolysis across the semipermeable inner membrane of the mitochondrion for oxidative phosphorylation in eukaryotes. These electrons enter the electron transport chain of the mitochondria via reduction equivalents to generate ATP. The shuttle system is required because the mitochondrial inner membrane is impermeable to NADH, the primary reducing equivalent of the electron transport chain. To circumvent this, malate carries the reducing equivalents across the membrane. Components The shuttle consists of four protein parts: * malate dehydrogenase in the mitochondrial matrix and intermembrane space. * aspartate aminotransferase in the mitochondrial matrix and intermembrane space. * malate-alpha-ketoglutarate antiporter in the inner membrane. * glutamate-aspartate antiporter in the inner membrane. Mechanism The primary enzyme in the malate-aspart ...
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Malate-aspartate Shuttle
The malate-aspartate shuttle (sometimes simply the malate shuttle) is a biochemical system for translocating electrons produced during glycolysis across the semipermeable inner membrane of the mitochondrion for oxidative phosphorylation in eukaryotes. These electrons enter the electron transport chain of the mitochondria via reduction equivalents to generate ATP. The shuttle system is required because the mitochondrial inner membrane is impermeable to NADH, the primary reducing equivalent of the electron transport chain. To circumvent this, malate carries the reducing equivalents across the membrane. Components The shuttle consists of four protein parts: * malate dehydrogenase in the mitochondrial matrix and intermembrane space. * aspartate aminotransferase in the mitochondrial matrix and intermembrane space. * malate-alpha-ketoglutarate antiporter in the inner membrane. * glutamate-aspartate antiporter in the inner membrane. Mechanism The primary enzyme in the malate-aspart ...
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Mitochondrial 2-oxoglutarate/malate Carrier Protein
Mitochondrial 2-oxoglutarate/malate carrier protein is a protein that in humans is encoded by the ''SLC25A11'' gene. Inactivating mutations in this gene predispose to metastasic paraganglioma A paraganglioma is a rare neuroendocrine neoplasm that may develop at various body sites (including the head, neck, thorax and abdomen). When the same type of tumor is found in the adrenal gland, they are referred to as a pheochromocytoma. They a .... See also * Solute carrier family References Further reading * * * * * * * * * * Solute carrier family {{membrane-protein-stub ...
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Glycerol Phosphate Shuttle
The glycerol-3-phosphate shuttle is a mechanism that regenerates NAD+ from NADH, a by-product of glycolysis. The shuttle consists of the sequential activity of two proteins: GPD1 which transfers an electron pair from NADH to dihydroxyacetone phosphate (DHAP), forming glycerol-3-phosphate (G3P) and regenerating NAD+ needed to generate energy via glycolysis. The mitochondrial inner membrane protein GPD2 catalyzes the oxidation of G3P, regenerating DHAP in the cytosol and forming FADH2 in the mitochondrial matrix. In mammals, its activity in transporting reducing equivalents across the mitochondrial membrane is considered secondary to the malate-aspartate shuttle. History The glycerol phosphate shuttle was first characterized as a major route of mitochondrial hydride transport in the flight muscles of blow flies. It was initially believed that the system would be inactive in mammals due to the predominance of lactate dehydrogenase activity over Glycerol-3-phosphate dehydrogenase 1 ...
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Pancreatic Cancer
Pancreatic cancer arises when cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a mass. These cancerous cells have the ability to invade other parts of the body. A number of types of pancreatic cancer are known. The most common, pancreatic adenocarcinoma, accounts for about 90% of cases, and the term "pancreatic cancer" is sometimes used to refer only to that type. These adenocarcinomas start within the part of the pancreas that makes digestive enzymes. Several other types of cancer, which collectively represent the majority of the non-adenocarcinomas, can also arise from these cells. About 1–2% of cases of pancreatic cancer are neuroendocrine tumors, which arise from the hormone-producing cells of the pancreas. These are generally less aggressive than pancreatic adenocarcinoma. Signs and symptoms of the most-common form of pancreatic cancer may include yellow skin, abdominal or back pain, unexplained weight loss, ...
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Cellular Respiration
Cellular respiration is the process by which biological fuels are oxidised in the presence of an inorganic electron acceptor such as oxygen to produce large amounts of energy, to drive the bulk production of ATP. Cellular respiration may be described as a set of metabolic reactions and processes that take place in the cells of organisms to convert chemical energy from nutrients into adenosine triphosphate (ATP), and then release waste products. The reactions involved in respiration are catabolic reactions, which break large molecules into smaller ones, releasing energy. Respiration is one of the key ways a cell releases chemical energy to fuel cellular activity. The overall reaction occurs in a series of biochemical steps, some of which are redox reactions. Although cellular respiration is technically a combustion reaction, it is an unusual one because of the slow, controlled release of energy from the series of reactions. Nutrients that are commonly used by animal and pl ...
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CARM1
CARM1 (coactivator-associated arginine methyltransferase 1), also known as PRMT4 (protein arginine N-methyltransferase 4), is an enzyme () encoded by the gene found in human beings, as well as many other mammals. It has a polypeptide (L) chain type that is 348 residues long, and is made up of alpha helices and beta sheets. Its main function includes catalyzing the transfer of a methyl group from S-Adenosyl methionine to the side chain nitrogens of arginine residues within proteins to form methylated arginine derivatives and S-Adenosyl-L-homocysteine. CARM1 is a secondary coactivator through its association with p160 family (SRC-1, GRIP1, AIB) of coactivators. It is responsible for moving cells toward the inner cell mass in developing blastocysts. Clinical significance CARM1 plays an important role in androgen receptors and may play a role in prostate cancer progression. CARM1 exerts both oncogenic and tumor-suppressive functions. In breast cancer, CARM1 methylates chromatin ...
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MDH1
Malate dehydrogenase, cytoplasmic also known as malate dehydrogenase 1 is an enzyme that in humans is encoded by the MDH1 gene. Function Malate dehydrogenase catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle. The protein encoded by this gene is localized to the cytoplasm and may play pivotal roles in the malate-aspartate shuttle that operates in the metabolic coordination between cytosol and mitochondria. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. Regulation The acetylation of MDH1 activates its enzymatic activity and enhance intracellular levels of NADPH, which promotes adipogenic differentiation. Methylation on arginine 248 (R248) negatively regulates MDH1. Protein arginine methyltransferase 4 (PRMT4/CARM1) methylates and inhibits MDH1 by disrupting its dimerization. Arginine methylation of MDH1 represses mitochondria respiration and inhibit ...
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Glycerol 3-phosphate Shuttle
The glycerol-3-phosphate shuttle is a mechanism that regenerates NAD+ from NADH, a by-product of glycolysis. The shuttle consists of the sequential activity of two proteins: GPD1 which transfers an electron pair from NADH to dihydroxyacetone phosphate (DHAP), forming glycerol-3-phosphate (G3P) and regenerating NAD+ needed to generate energy via glycolysis. The mitochondrial inner membrane protein GPD2 catalyzes the oxidation of G3P, regenerating DHAP in the cytosol and forming FADH2 in the mitochondrial matrix. In mammals, its activity in transporting reducing equivalents across the mitochondrial membrane is considered secondary to the malate-aspartate shuttle. History The glycerol phosphate shuttle was first characterized as a major route of mitochondrial hydride transport in the flight muscles of blow flies. It was initially believed that the system would be inactive in mammals due to the predominance of lactate dehydrogenase activity over Glycerol-3-phosphate dehydrogenase 1 ( ...
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Redox
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a decrease in the oxidation state. There are two classes of redox reactions: * ''Electron-transfer'' – Only one (usually) electron flows from the reducing agent to the oxidant. This type of redox reaction is often discussed in terms of redox couples and electrode potentials. * ''Atom transfer'' – An atom transfers from one substrate to another. For example, in the rusting of iron, the oxidation state of iron atoms increases as the iron converts to an oxide, and simultaneously the oxidation state of oxygen decreases as it accepts electrons released by the iron. Although oxidation reactions are commonly associated with the formation of oxides, other chemical species can serve the same function. In hydrogenation, C=C (and other) bonds ...
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Glutamate Aspartate Transporter
Excitatory amino acid transporter 1 (EAAT1) is a protein that, in humans, is encoded by the ''SLC1A3'' gene. EAAT1 is also often called the GLutamate ASpartate Transporter 1 (GLAST-1). EAAT1 is predominantly expressed in the plasma membrane, allowing it to remove glutamate from the extracellular space. It has also been localized in the inner mitochondrial membrane as part of the malate-aspartate shuttle. Mechanism EAAT1 functions ''in vivo'' as a homotrimer. EAAT1 mediates the transport of glutamic and aspartic acid with the cotransport of three Na+ and one H+ cations and counter transport of one K+ cation. This co-transport coupling (or symport) allows the transport of glutamate into cells against a concentration gradient. Tissue distribution EAAT1 is expressed throughout the CNS, and is highly expressed in astrocytes and Bergmann glia in the cerebellum. In the retina, EAAT1 is expressed in Muller cells. EAAT1 is also expressed in a number of other tissues ...
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Oxaloacetate
Oxaloacetic acid (also known as oxalacetic acid or OAA) is a crystalline organic compound with the chemical formula HO2CC(O)CH2CO2H. Oxaloacetic acid, in the form of its conjugate base oxaloacetate, is a metabolic intermediate in many processes that occur in animals. It takes part in gluconeogenesis, the urea cycle, the glyoxylate cycle, amino acid synthesis, fatty acid synthesis and the citric acid cycle. Properties Oxaloacetic acid undergoes successive deprotonations to give the dianion: :HO2CC(O)CH2CO2H −O2CC(O)CH2CO2H + H+, pKa = 2.22 :−O2CC(O)CH2CO2H −O2CC(O)CH2CO2− + H+, pKa = 3.89 At high pH, the enolizable proton is ionized: :−O2CC(O)CH2CO2− −O2CC(O−)CHCO2− + H+, pKa = 13.03 The enol forms of oxaloacetic acid are particularly stable, so much so that the two tautomers have different melting points (152 °C for the ''cis'' isoform and 184 °C for the ''trans'' isoform). This reaction is catalyzed by the enzyme oxaloacetate ...
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