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Pyrimidine Phosphoribosyltransferase
Orotate phosphoribosyltransferase (OPRTase) or orotic acid phosphoribosyltransferase is an enzyme involved in pyrimidine biosynthesis. It catalyzes the formation of orotidine 5'-monophosphate (OMP) from orotate and phosphoribosyl pyrophosphate. In yeast and bacteria, orotate phosphoribosyltransferase is an independent enzyme with a unique gene coding for the protein, whereas in mammals and other multicellular organisms, the catalytic function is carried out by a domain of the bifunctional enzyme UMP synthase (UMPS). Biological background As OPRTase is part of a bifunctional complex UMP synthase in humans, the function and stability of this enzyme is not necessarily directly associated with disorders in the human body. It is however reasonable to believe that a dysfunction in one of the enzymes will cause a dysfunction of the whole enzyme. Defects in UMP synthase is associated with hypochromic anemia. In mammals, this bifunctional enzyme UMPS converts orotic acid into uridine ...
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Enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. Almost all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called ''enzymology'' and the field of pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts are catalytic RNA molecules, called ribozymes. Enzymes' specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the reaction ra ...
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Orotidine 5'-monophosphate
Orotidine 5'-monophosphate (OMP), also known as orotidylic acid, is a pyrimidine nucleotide which is the last intermediate in the biosynthesis of uridine monophosphate. OMP is formed from orotate and phosphoribosyl pyrophosphate by the enzyme orotate phosphoribosyltransferase In humans, the enzyme UMP synthase converts OMP into uridine 5'- monophosphate. If UMP synthase is defective, orotic aciduria Orotic aciduria (AKA hereditary orotic aciduria) is a disease caused by an enzyme deficiency resulting in a decreased ability to synthesize pyrimidines. It was the first described enzyme deficiency of the ''de novo'' pyrimidine synthesis pathway. ... can result. Nucleotides Pyrimidinediones {{biochem-stub ...
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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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UMP Kinase
In enzymology, an UMP kinase () is an enzyme that catalyzes the chemical reaction :ATP + UMP \rightleftharpoons ADP + UDP Thus, the two substrates of this enzyme are ATP and UMP, whereas its two products are ADP and UDP. This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing groups (phosphotransferases) with a phosphate group as acceptor. The systematic name of this enzyme class is ATP:UMP phosphotransferase. Other names in common use include uridylate kinase, UMPK, uridine monophosphate kinase, PyrH, UMP-kinase, and SmbA. This enzyme participates in pyrimidine metabolism. Structural studies As of March 2010, 19 structures have been solved for this class of enzymes, and are deposited in the PDB. All have a 3-layer (aba) sandwich) architecture (CATH The CATH Protein Structure Classification database is a free, publicly available online resource that provides information on the evolutionary relationships of protein domains. ...
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Phosphorylation
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, which is available under a Creative Commons Attribution 4.0 International License. Protein phosphorylation often activates (or deactivates) many enzymes. Glucose Phosphorylation of sugars is often the first stage in their catabolism. Phosphorylation allows cells to accumulate sugars because the phosphate group prevents the molecules from diffusing back across their transporter. Phosphorylation of glucose is a key reaction in sugar metabolism. The chemical equation for the conversion of D-glucose to D-glucose-6-phosphate in the first step of glycolysis is given by :D-glucose + ATP → D-glucose-6-phosphate + ADP : ΔG° = −16.7 kJ/mol (° indicates measurement at standard condition) Hepatic cells are freely permeable to glucose, and ...
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Uridine Diphosphate
Uridine diphosphate, abbreviated UDP, is a nucleotide diphosphate. It is an ester of pyrophosphoric acid with the nucleoside uridine. UDP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase uracil. UDP is an important factor in glycogenesis. Before glucose can be stored as glycogen in the liver and muscles, the enzyme UDP-glucose pyrophosphorylase forms a UDP-glucose unit by combining glucose 1-phosphate with uridine triphosphate, cleaving a pyrophosphate ion in the process. Then, the enzyme glycogen synthase combines UDP-glucose units to form a glycogen chain. The UDP molecule is cleaved from the glucose ring during this process and can be reused by UDP-glucose pyrophosphorylase. See also * DNA * Nucleoside * Nucleotide * Oligonucleotide * RNA * UGGT UGGT, or UDP-glucose:glycoprotein glucosyltransferase, is a soluble enzyme resident in the lumen of the endoplasmic reticulum (ER). The main function of UGGT is to recognize misfolded glycoprotein ...
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Nucleotide
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are obtained in the diet and are also synthesized from common nutrients by the liver. Nucleotides are composed of three subunit molecules: a nucleobase, a five-carbon sugar (ribose or deoxyribose), and a phosphate group consisting of one to three phosphates. The four nucleobases in DNA are guanine, adenine, cytosine and thymine; in RNA, uracil is used in place of thymine. Nucleotides also play a central role in metabolism at a fundamental, cellular level. They provide chemical energy—in the form of the nucleoside triphosphates, adenosine triphosphate (ATP), guanosine triphosphate (GTP), cytidine triphosphate (CTP) and uridine triphosphate (UTP)—throughout the cell for the many cellular func ...
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Uridine Monophosphate
Uridine monophosphate (UMP), also known as 5′-uridylic acid (conjugate base uridylate), is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid with the nucleoside uridine. UMP consists of the phosphate group, the pentose sugar ribose, and the nucleobase uracil; hence, it is a ribonucleotide monophosphate. As a substituent or radical its name takes the form of the prefix uridylyl-. The deoxy form is abbreviated dUMP. Covalent attachment of UMP (e.g. to a protein such as adenylyltransferase) is called uridylylation (or sometimes uridylation). Biosynthesis Uridine monophosphate is formed from Orotidine 5'-monophosphate (orotidylic acid) in a decarboxylation reaction catalyzed by the enzyme orotidylate decarboxylase. Uncatalyzed, the decarboxylation reaction is extremely slow (estimated to occur on average one time per 78 million years). Adequately catalyzed, the reaction takes place once per second, an increase of 1017-fold. In humans, the orotidyl ...
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Auxotrophy
Auxotrophy ( grc, αὐξάνω "to increase"; ''τροφή'' "nourishment") is the inability of an organism to synthesize a particular organic compound required for its growth (as defined by IUPAC). An auxotroph is an organism that displays this characteristic; ''auxotrophic'' is the corresponding adjective. Auxotrophy is the opposite of prototrophy, which is characterized by the ability to synthesize all the compounds needed for growth. Prototrophic cells (also referred to as the 'wild type') are self sufficient producers of all required metabolites (e.g. amino acids, lipids, cofactors), while auxotrophs require to be on medium with the metabolite that they cannot produce. For example saying a cell is methionine auxotrophic means that it would need to be on a medium containing methionine or else it would not be able to replicate. In this example this is because it is unable to produce its own methionine (methionine auxotroph). However, a prototroph or a methionine prototrophic ce ...
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Decarboxylation
Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carboxylation, the addition of CO2 to a compound. Enzymes that catalyze decarboxylations are called decarboxylases or, the more formal term, carboxy-lyases (Enzyme Commission number, EC number 4.1.1). In organic chemistry The term "decarboxylation" usually means replacement of a carboxyl group () with a hydrogen atom: :RCO2H -> RH + CO2 Decarboxylation is one of the oldest known organic reactions. It is one of the processes assumed to accompany pyrolysis and destructive distillation. Metal salts, especially copper compounds, facilitate the reaction via the intermediacy of metal carboxylate complexes. Decarboxylation of aryl carboxylates can generate the equivalent of the correspond ...
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Orotidylate
Orotidine 5'-monophosphate (OMP), also known as orotidylic acid, is a pyrimidine nucleotide which is the last intermediate in the biosynthesis of uridine monophosphate. OMP is formed from orotate and phosphoribosyl pyrophosphate by the enzyme orotate phosphoribosyltransferase Orotate phosphoribosyltransferase (OPRTase) or orotic acid phosphoribosyltransferase is an enzyme involved in pyrimidine biosynthesis. It catalyzes the formation of orotidine 5'-monophosphate (OMP) from orotate and phosphoribosyl pyrophosphate. ... In humans, the enzyme UMP synthase converts OMP into uridine 5'- monophosphate. If UMP synthase is defective, orotic aciduria can result. Nucleotides Pyrimidinediones {{biochem-stub ...
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Orotidine 5'-phosphate Decarboxylase
Orotidine 5'-phosphate decarboxylase (OMP decarboxylase) or orotidylate decarboxylase is an enzyme involved in pyrimidine biosynthesis. It catalyzes the decarboxylation of orotidine monophosphate (OMP) to form uridine monophosphate (UMP). The function of this enzyme is essential to the de novo biosynthesis of the pyrimidine nucleotides uridine triphosphate, cytidine triphosphate, and thymidine triphosphate. OMP decarboxylase has been a frequent target for scientific investigation because of its demonstrated extreme catalytic efficiency and its usefulness as a selection marker for yeast strain engineering. Catalysis OMP decarboxylase is known for being an extraordinarily efficient catalyst capable of accelerating the uncatalyzed reaction rate by a factor of 1017. To put this in perspective, the uncatalysed reaction which would take ''78 million years'' to convert half the reactants into products is accelerated to ''18 milliseconds'' when catalyzed by OMP decarboxylase. This ...
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