Glutamate–glutamine Cycle
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Glutamate–glutamine Cycle
In biochemistry, the glutamate–glutamine cycle is a cyclic metabolic pathway which maintains an adequate supply of the neurotransmitter glutamate in the central nervous system. Neurons are unable to synthesize either the excitatory neurotransmitter glutamate, or the inhibitory GABA from glucose. Discoveries of glutamate and glutamine pools within intercellular compartments led to suggestions of the glutamate–glutamine cycle working between neurons and astrocytes. The glutamate/GABA–glutamine cycle is a metabolic pathway that describes the release of either glutamate or GABA from neurons which is then taken up into astrocytes (non-neuronal glial cells). In return, astrocytes release glutamine to be taken up into neurons for use as a precursor to the synthesis of either glutamate or GABA. Production Glutamate Initially, in a glutamatergic synapse, the neurotransmitter glutamate is released from the neurons and is taken up into the synaptic cleft. Glutamate residing in the syna ...
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Biochemistry
Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, and metabolism. Over the last decades of the 20th century, biochemistry has become successful at explaining living processes through these three disciplines. Almost all List of life sciences, areas of the life sciences are being uncovered and developed through biochemical methodology and research.#Voet, Voet (2005), p. 3. Biochemistry focuses on understanding the chemical basis that allows biomolecule, biological molecules to give rise to the processes that occur within living Cell (biology), cells and between cells,#Karp, Karp (2009), p. 2. in turn relating greatly to the understanding of tissue (biology), tissues and organ (anatomy), organs as well as organism structure and function.#Miller, Miller (2012). p. 62. Biochemistry is closely ...
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VGLUT
Glutamate transporters are a family of neurotransmitter transporter proteins that move glutamate – the principal excitatory neurotransmitter – across a membrane. The family of glutamate transporters is composed of two primary subclasses: the excitatory amino acid transporter (EAAT) family and vesicular glutamate transporter (VGLUT) family. In the brain, EAATs remove glutamate from the synaptic cleft and extrasynaptic sites via glutamate reuptake into glial cells and neurons, while VGLUTs move glutamate from the cell cytoplasm into synaptic vesicles. Glutamate transporters also transport aspartate and are present in virtually all peripheral tissues, including the heart, liver, testes, and bone. They exhibit stereoselectivity for L-glutamate but transport both L-aspartate and D-aspartate. The EAATs are membrane-bound secondary transporters that superficially resemble ion channels. These transporters play the important role of regulating concentrations of glutamate in the extracell ...
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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. Keto-enol tautomerization is catalyzed by the enzyme oxaloacetate tautomerase. ''trans''-Enol-oxaloacetate also appears when tartrate is the substrate for fumarase. Biosynthesis Oxaloacetate forms ...
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Succinate-semialdehyde Dehydrogenase
In enzymology, a succinate-semialdehyde dehydrogenase (SSADH) () is an enzyme that catalyzes the chemical reaction :succinate semialdehyde + NAD+ + H2O succinate + NADH + 2 H+ The 3 substrates of this enzyme are succinate semialdehyde, NAD+, and H2O, whereas its 3 products are succinate, NADH, and H+. This enzyme belongs to the family of oxidoreductases, specifically those acting on the aldehyde or oxo group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is succinate-semialdehyde:NAD+ oxidoreductase. Other names in common use include succinate semialdehyde dehydrogenase, succinic semialdehyde dehydrogenase, succinyl semialdehyde dehydrogenase, and succinate semialdehyde:NAD+ oxidoreductase. This enzyme participates in glutamate and butyrate metabolism. Succinate-semialdehyde dehydrogenase is found in organisms ranging across the tree of life from bacteria to humans. It is important in the degradation of γ-aminobutyric acid in humans, a ...
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GABA Transaminase
In enzymology, 4-aminobutyrate transaminase (), also called GABA transaminase or 4-aminobutyrate aminotransferase, or GABA-T, is an enzyme that catalysis, catalyzes the chemical reaction: :4-aminobutanoate + 2-oxoglutarate \rightleftharpoons succinate semialdehyde + L-glutamate Thus, the two substrate (biochemistry), substrates of this enzyme are 4-aminobutanoate (GABA) and 2-oxoglutarate. The two product (chemistry), products are succinate semialdehyde and L-glutamate. This enzyme belongs to the family of transferases, specifically the transaminases, which transfer nitrogenous groups. The List of enzymes, systematic name of this enzyme class is 4-aminobutanoate:2-oxoglutarate aminotransferase. This enzyme participates in 5 metabolic pathways: alanine and aspartate metabolism, glutamate metabolism, beta-alanine metabolism, propanoate metabolism, and butyric acid, butanoate metabolism. It employs one cofactor (biochemistry), cofactor, pyridoxal phosphate. This enzyme is found in ...
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Succinate
Succinic acid () is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological roles as a metabolic intermediate being converted into Fumaric acid, fumarate by the enzyme succinate dehydrogenase in complex 2 of the electron transport chain which is involved in making Adenosine triphosphate, ATP, and as a signaling molecule reflecting the cellular metabolic state. Succinate is generated in mitochondria via the citric acid cycle, tricarboxylic acid (TCA) cycle. Succinate can exit the mitochondrial matrix and function in the cytoplasm as well as the extracellular space, changing gene expression patterns, modulating epigenetic landscape or demonstrating hormone-like signaling. As such, succinate links cellular metabolism, especially ATP formation, to the regulation of cellular function. Dysregulation of succinate synthesis, and therefore ATP synthesis, happens in some genetic m ...
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Catabolized
Catabolism () is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipids, nucleic acids, and proteins) into smaller units (such as monosaccharides, fatty acids, nucleotides, and amino acids, respectively). Catabolism is the breaking-down aspect of metabolism, whereas anabolism is the building-up aspect. Cells use the monomers released from breaking down polymers to either construct new polymer molecules or degrade the monomers further to simple waste products, releasing energy. Cellular wastes include lactic acid, acetic acid, carbon dioxide, ammonia, and urea. The formation of these wastes is usually an oxidation process involving a release of chemical free energy, some of which is lost as heat, but the rest of which is used to drive the synthesis of adenosine triphosphate (ATP). This molecule acts as a way ...
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GABA Transporter
GABA transporters (gamma-aminobutyric acid Neurotransmitter transporter, transporters) are a family of neurotransmitter / sodium Symporter, symporters, belonging to the Solute carrier family, solute carrier 6 (SLC6) family. They are found in various regions of the brain in different cell types, such as neurons and astrocytes. These transporters are primarily responsible for the regulation of extracellular GABA concentration during basal and synaptic activity. They are responsible for creating a GABA gradient which is determined by the membrane potential, and the concentration of Na+ and Cl−. They are also present on the plasma membrane of neurons and glia which help define their function of regulation of GABA concentration as they act as the receptors that facilitate recycling of GABA in the extracellular space. GABA transporters are a common target for anticonvulsant drugs against seizure disorders such as epilepsy. Types The GABA transporter group consists of six different tr ...
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Astrocytes
Astrocytes (from Ancient Greek , , "star" and , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endothelial cells that form the blood–brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, regulation of cerebral blood flow, and a role in the repair and Glial scar, scarring process of the brain and spinal cord following infection and traumatic injuries. The proportion of astrocytes in the brain is not well defined; depending on the counting technique used, studies have found that the astrocyte proportion varies by region and ranges from 20% to around 40% of all glia. Another study reports that astrocytes are the most numerous cell type in the brain. Astrocytes are the major source of cholesterol in the central nervous system. Apolipoprotein E transports cholesterol from astrocytes to neuro ...
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Glutamate Decarboxylase
Glutamate decarboxylase or glutamic acid decarboxylase (GAD) is an enzyme that catalyzes the Decarboxylation#Decarboxylation of amino acids, decarboxylation of glutamate to gamma-aminobutyric acid (GABA) and carbon dioxide (). GAD uses pyridoxal-phosphate (PLP) as a cofactor (biochemistry), cofactor. The reaction proceeds as follows: : In mammals, GAD exists in two isoforms with molecular weights of 67 and 65 Dalton (unit), kDa (GAD67 and GAD65), which are encoded by two different genes on different chromosomes (''GAD1'' and ''GAD2'' genes, Chromosome 2, chromosomes 2 and Chromosome 10, 10 in humans, respectively). GAD67 and GAD65 are expressed in the brain where GABA is used as a neurotransmitter, and they are also expressed in the insulin-producing beta cell, β-cells of the pancreas, in varying ratios depending upon the species. Together, these two enzymes maintain the major physiological supply of GABA in mammals, though it may also be synthesized from putrescine in the ent ...
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Citric Acid Cycle
The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle (tricarboxylic acid cycle)—is a series of chemical reaction, biochemical reactions that release the energy stored in nutrients through acetyl-CoA Redox, oxidation. The energy released is available in the form of Adenosine triphosphate, ATP. The Hans Krebs (biochemist), Krebs cycle is used by organisms that generate energy via Cellular respiration, respiration, either anaerobic respiration, anaerobically or aerobic respiration, aerobically (organisms that Fermentation, ferment use different pathways). In addition, the cycle provides precursor (chemistry), precursors of certain amino acids, as well as the reducing agent nicotinamide adenine dinucleotide, NADH, which are used in other reactions. Its central importance to many Metabolic pathway, biochemical pathways suggests that it was one of the earliest metabolism components. Even though it is branded as a "cycle", it is not necessa ...
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