Gamma-Glutamylcysteine
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Gamma-Glutamylcysteine
γ -L-Glutamyl-L-cysteine, also known as γ-glutamylcysteine (GGC), is a dipeptide found in animals, plants, fungi, some bacteria, and archaea. It has a relatively unusual γ-bond between the constituent amino acids, L-glutamic acid and L-cysteine and is a key intermediate in the gamma (γ) -glutamyl cycle first described by Meister in the 1970s. It is the most immediate precursor to the antioxidant glutathione. Biosynthesis GGC is synthesized from L-glutamic acid and L-cysteine in the cytoplasm of virtually all cells in an adenosine triphosphate (ATP) requiring reaction catalysed by the enzyme glutamate-cysteine ligase (GCL, EC 6.3.2.2; formerly γ-glutamylcysteine synthetase).  The production of GGC is the rate limiting step in glutathione synthesis. Occurrence GGC occurs in human plasma in the range of 1 – 5 µM and intracellularly at 5 – 10 µM. The intracellular concentration is generally low because GGC is rapidly bonded with a glycine to form glutathione.  ...
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Tiopronin
Tiopronin, sold under the brand name Thiola, is a medication used to control the rate of cystine precipitation and excretion in the disease cystinuria. Due to the rarity of the disorder, tiopronin falls under the classification of an orphan drug. It is somewhat similar to penicillamine in both chemistry and pharmacology. A generic version of tiopronin is available in the United States as of April 2021. Uses Tiopronin is used primarily for cystinuria and is well known in the cystinuric community. Depending on the severity of a person's cystinuria, tiopronin may be taken for life, possibly starting in early childhood. The drug works by reacting with urinary cysteine to form a more soluble, disulfide linked, tiopronin-cysteine complex. Side effects Tiopronin may present a variety of side effects, which are broadly similar to those of D-penicillamine and other compounds containing active sulfhydryl groups. Its pharmacokinetics have been studied. Society and culture In the U.S., th ...
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Adenosine Triphosphate
Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of life, ATP is often referred to as the "molecular unit of currency" of intracellular energy transfer. When consumed in metabolic processes, it converts either to adenosine diphosphate (ADP) or to adenosine monophosphate (AMP). Other processes regenerate ATP. The human body recycles its own body weight equivalent in ATP each day. It is also a precursor to DNA and RNA, and is used as a coenzyme. From the perspective of biochemistry, ATP is classified as a nucleoside triphosphate, which indicates that it consists of three components: a nitrogenous base (adenine), the sugar ribose, and the Polyphosphate, triphosphate. Structure ATP consists of an adenine attached by the 9-nitrogen atom to the 1′ carbon atom of a sugar (ribose), which i ...
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Knockout Mouse
A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are important animal models for studying the role of genes which have been sequenced but whose functions have not been determined. By causing a specific gene to be inactive in the mouse, and observing any differences from normal behaviour or physiology, researchers can infer its probable function. Mice are currently the laboratory animal species most closely related to humans for which the knockout technique can easily be applied. They are widely used in knockout experiments, especially those investigating genetic questions that relate to human physiology. Gene knockout in rats is much harder and has only been possible since 2003. The first recorded knockout mouse was created by Mario R. Capecchi, Martin Evans, and Oliver Smithies in 1989, for whi ...
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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 basic unit of heredity and 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: protein-coding genes and noncoding genes. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as gen ...
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Mammal
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or hair, and three middle ear bones. These characteristics distinguish them from reptiles (including birds) from which they diverged in the Carboniferous, over 300 million years ago. Around 6,400 extant species of mammals have been described divided into 29 orders. The largest orders, in terms of number of species, are the rodents, bats, and Eulipotyphla (hedgehogs, moles, shrews, and others). The next three are the Primates (including humans, apes, monkeys, and others), the Artiodactyla ( cetaceans and even-toed ungulates), and the Carnivora (cats, dogs, seals, and others). In terms of cladistics, which reflects evolutionary history, mammals are the only living members of the Synapsida (synapsids); this clade, together with Saur ...
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Glutathione Synthetase
Glutathione synthetase (GSS) () is the second enzyme in the glutathione (GSH) biosynthesis pathway. It catalyses the condensation of gamma-glutamylcysteine and glycine, to form glutathione. Glutathione synthetase is also a potent antioxidant. It is found in many species including bacteria, yeast, mammals, and plants. In humans, defects in GSS are inherited in an autosomal recessive way and are the cause of severe metabolic acidosis, 5-oxoprolinuria, increased rate of haemolysis, and defective function of the central nervous system. Deficiencies in GSS can cause a spectrum of deleterious symptoms in plants and human beings alike. In eukaryotes, this is a homodimeric enzyme. The substrate-binding domain has a three-layer alpha/beta/alpha structure. This enzyme utilizes and stabilizes an acylphosphate intermediate to later perform a favorable nucleophilic attack of glycine. Structure Human and yeast glutathione synthetases are homodimers, meaning they are composed of two i ...
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Biosynthesis
Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. This process often consists of metabolic pathways. Some of these biosynthetic pathways are located within a single cellular organelle, while others involve enzymes that are located within multiple cellular organelles. Examples of these biosynthetic pathways include the production of lipid membrane components and nucleotides. Biosynthesis is usually synonymous with anabolism. The prerequisite elements for biosynthesis include: precursor compounds, chemical energy (e.g. ATP), and catalytic enzymes which may require coenzymes (e.g.NADH, NADPH). These elements create monomers, the building blocks for macromolecules. Some important biological macromolecules include: proteins, which are composed of amino acid monomers joined via peptide bon ...
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Chemical Reaction
A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and breaking of chemical bonds between atoms, with no change to the Atomic nucleus, nuclei (no change to the elements present), and can often be described by a chemical equation. Nuclear chemistry is a sub-discipline of chemistry that involves the chemical reactions of unstable and radioactive Chemical element, elements where both electronic and nuclear changes can occur. The substance (or substances) initially involved in a chemical reaction are called reagent, reactants or reagents. Chemical reactions are usually characterized by a chemical change, and they yield one or more Product (chemistry), products, which usually have properties different from the reactants. Reactions often consist of a sequence o ...
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Glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (GGU, GGC, GGA, GGG). Glycine is integral to the formation of alpha-helices in secondary protein structure due to its compact form. For the same reason, it is the most abundant amino acid in collagen triple-helices. Glycine is also an inhibitory neurotransmitter – interference with its release within the spinal cord (such as during a ''Clostridium tetani'' infection) can cause spastic paralysis due to uninhibited muscle contraction. It is the only achiral proteinogenic amino acid. It can fit into hydrophilic or hydrophobic environments, due to its minimal side chain of only one hydrogen atom. History and etymology Glycine was discovered in 1820 by the French chemist He ...
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Chemical Bond
A chemical bond is a lasting attraction between atoms or ions that enables the formation of molecules and crystals. The bond may result from the electrostatic force between oppositely charged ions as in ionic bonds, or through the sharing of electrons as in covalent bonds. The strength of chemical bonds varies considerably; there are "strong bonds" or "primary bonds" such as covalent, ionic and metallic bonds, and "weak bonds" or "secondary bonds" such as dipole–dipole interactions, the London dispersion force and hydrogen bonding. Strong chemical bonding arises from the sharing or transfer of electrons between the participating atoms. Since opposite electric charges attract, the negatively charged electrons surrounding the nucleus and the positively charged protons within a nucleus attract each other. An electron positioned between two nuclei will be attracted to both of them, and the nuclei will be attracted toward electrons in this position. This attraction constitu ...
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Blood Plasma
Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intravascular part of extracellular fluid (all body fluid outside cells). It is mostly water (up to 95% by volume), and contains important dissolved proteins (6–8%; e.g., serum albumins, globulins, and fibrinogen), glucose, clotting factors, electrolytes (, , , , , etc.), hormones, carbon dioxide (plasma being the main medium for excretory product transportation), and oxygen. It plays a vital role in an intravascular osmotic effect that keeps electrolyte concentration balanced and protects the body from infection and other blood-related disorders. Blood plasma is separated from the blood by spinning a vessel of fresh blood containing an anticoagulant in a centrifuge until the blood cells fall to the bottom of the tube. The blood plasma is t ...
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Rate-determining Step
In chemical kinetics, the overall rate of a reaction is often approximately determined by the slowest step, known as the rate-determining step (RDS or RD-step or r/d step) or rate-limiting step. For a given reaction mechanism, the prediction of the corresponding rate equation (for comparison with the experimental rate law) is often simplified by using this approximation of the rate-determining step. In principle, the time evolution of the reactant and product concentrations can be determined from the set of simultaneous rate equations for the individual steps of the mechanism, one for each step. However, the analytical solution of these differential equations is not always easy, and in some cases numerical integration may even be required. The hypothesis of a single rate-determining step can greatly simplify the mathematics. In the simplest case the initial step is the slowest, and the overall rate is just the rate of the first step. Also, the rate equations for mechanisms with a s ...
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