Carbamoyl-phosphate Synthase (glutamine-hydrolysing)
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Carbamoyl-phosphate Synthase (glutamine-hydrolysing)
Carbamoyl phosphate synthetase (glutamine-hydrolysing) () is an enzyme that catalyzes the reactions that produce carbamoyl phosphate in the cytosol (as opposed to type I, which functions in the mitochondria). Its systemic name is ''hydrogen-carbonate:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating)''. In pyrimidine biosynthesis, it serves as the rate-limiting enzyme and catalyzes the following reaction: : 2 ATP + L- glutamine + HCO3− + H2O \rightleftharpoons 2 ADP + phosphate + L-glutamate + carbamoyl phosphate (overall reaction) : (1a) L-glutamine + H2O \rightleftharpoons L-glutamate + NH3 : (1b) 2 ATP + HCO3− + NH3 \rightleftharpoons 2 ADP + phosphate + carbamoyl phosphate It is activated by ATP and PRPP and it is inhibited by UMP ( Uridine monophosphate, the end product of the pyrimidine synthesis pathway). Neither CPSI nor CPSII require biotin as a coenzyme, as seen with most carboxylation reactions. It is one of the three enzyme functions coded by ...
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Carbamoyl Phosphate
Carbamoyl phosphate is an anion of biochemical significance. In land-dwelling animals, it is an intermediary metabolite in nitrogen disposal through the urea cycle and the synthesis of pyrimidines. Its enzymatic counterpart, carbamoyl phosphate synthetase I (CPS I), interacts with a class of molecules called sirtuins, NAD dependent protein deacetylases, and ATP to form carbamoyl phosphate. CP then enters the urea cycle in which it reacts with ornithine (a process catalyzed by the enzyme ornithine transcarbamylase) to form citrulline. Production It is produced from bicarbonate, ammonia (derived from amino acids), and phosphate (from ATP). The synthesis is catalyzed by the enzyme carbamoyl phosphate synthetase. This uses three reactions as follows: * + ATP → ADP + (carboxyl phosphate) * + NH3 + OH− → + −O–C(O)NH2 + H2O *−O–C(O)NH2 + ATP → ADP + Clinical significance A defect in the CPS I enzyme, and a subsequent deficiency in the production of ...
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Cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into many compartments. In the eukaryotic cell, the cytosol is surrounded by the cell membrane and is part of the cytoplasm, which also comprises the mitochondria, plastids, and other organelles (but not their internal fluids and structures); the cell nucleus is separate. The cytosol is thus a liquid matrix around the organelles. In prokaryotes, most of the chemical reactions of metabolism take place in the cytosol, while a few take place in membranes or in the periplasmic space. In eukaryotes, while many metabolic pathways still occur in the cytosol, others take place within organelles. The cytosol is a complex mixture of substances dissolved in water. Although water forms the large majority of the cytosol, its structure and prope ...
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Mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used throughout the cell as a source of chemical energy. They were discovered by Albert von Kölliker in 1857 in the voluntary muscles of insects. The term ''mitochondrion'' was coined by Carl Benda in 1898. The mitochondrion is popularly nicknamed the "powerhouse of the cell", a phrase coined by Philip Siekevitz in a 1957 article of the same name. Some cells in some multicellular organisms lack mitochondria (for example, mature mammalian red blood cells). A large number of unicellular organisms, such as microsporidia, parabasalids and diplomonads, have reduced or transformed their mitochondria into mitosome, other structures. One eukaryote, ''Monocercomonoides'', is known to have completely lost its mitocho ...
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Pyrimidine
Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The other diazines are pyrazine (nitrogen atoms at the 1 and 4 positions) and pyridazine (nitrogen atoms at the 1 and 2 positions). In nucleic acids, three types of nucleobases are pyrimidine derivatives: cytosine (C), thymine (T), and uracil (U). Occurrence and history The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. It is also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. Although pyrimidine derivatives such as alloxan were known in the early 19th century, a laboratory synthesis of a pyrimidine was not carried out until 1879, when Grimaux reported the ...
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Glutamine
Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral, polar amino acid. It is non-essential and conditionally essential in humans, meaning the body can usually synthesize sufficient amounts of it, but in some instances of stress, the body's demand for glutamine increases, and glutamine must be obtained from the diet. It is encoded by the codons CAA and CAG. In human blood, glutamine is the most abundant free amino acid. The dietary sources of glutamine include especially the protein-rich foods like beef, chicken, fish, dairy products, eggs, vegetables like beans, beets, cabbage, spinach, carrots, parsley, vegetable juices and also in wheat, papaya, Brussels sprouts, celery, kale and fermented foods like miso. Functions Glutamine plays a role in a variety of biochemical functions: * Pr ...
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Phosphate
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosphoric acid by the removal of three protons . Removal of one or two protons gives the dihydrogen phosphate ion and the hydrogen phosphate ion ion, respectively. These names are also used for salts of those anions, such as ammonium dihydrogen phosphate and trisodium phosphate. File:3-phosphoric-acid-3D-balls.png, Phosphoricacid File:2-dihydrogenphosphate-3D-balls.png, Dihydrogenphosphate File:1-hydrogenphosphate-3D-balls.png, Hydrogenphosphate File:0-phosphate-3D-balls.png, Phosphate In organic chemistry, phosphate or orthophosphate is an organophosphate, an ester of orthophosphoric acid of the form where one or more hydrogen atoms are replaced by organic groups. An example is trimethyl phosphate, . The term also refers to the triv ...
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Glutamate
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synthesize enough for its use. It is also the most abundant excitatory neurotransmitter in the vertebrate nervous system. It serves as the precursor for the synthesis of the inhibitory gamma-aminobutyric acid (GABA) in GABA-ergic neurons. Its molecular formula is . Glutamic acid exists in three optically isomeric forms; the dextrorotatory -form is usually obtained by hydrolysis of gluten or from the waste waters of beet-sugar manufacture or by fermentation.Webster's Third New International Dictionary of the English Language Unabridged, Third Edition, 1971. Its molecular structure could be idealized as HOOC−CH()−()2−COOH, with two carboxyl groups −COOH and one amino group −. However, in the solid state and mildly acidic water solu ...
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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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PRPP
Phosphoribosyl pyrophosphate (PRPP) is a pentose phosphate. It is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, as well as in pyrimidine nucleotide formation. Hence it is a building block for DNA and RNA. The vitamins thiamine and cobalamin, and the amino acid tryptophan also contain fragments derived from PRPP. It is formed from ribose 5-phosphate (R5P) by the enzyme ribose-phosphate diphosphokinase: : It plays a role in transferring phospho-ribose groups in several reactions, some of which are salvage pathways: In '' de novo'' generation of purines, the enzyme amidophosphoribosyltransferase acts upon PRPP to create phosphoribosylamine. The histidine biosynthesis pathway involves the reaction between PRPP and ATP, which activates the latter to ring cleavage. Carbon atoms from ribose in PRPP form the linear chain and part of the imidazole ring in histidine. The same is true for the biosynthesis of tryptophan, with the first s ...
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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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Biotin
Biotin (or vitamin B7) is one of the B vitamins. It is involved in a wide range of metabolic processes, both in humans and in other organisms, primarily related to the utilization of fats, carbohydrates, and amino acids. The name ''biotin'', borrowed from the German , derives from the Ancient Greek word (; 'life') and the suffix "-in" (a suffix used in chemistry usually to indicate 'forming'). Chemical description Biotin is classified as a heterocyclic compound, with a sulfur-containing ring fused ureido and tetrahydrothiophene group. A C5-carboxylic acid side chain is appended to one of the rings. The ureido ring, containing the −N−CO−N− group, serves as the carbon dioxide carrier in carboxylation reactions. Biotin is a coenzyme for five carboxylase enzymes, which are involved in the catabolism of amino acids and fatty acids, synthesis of fatty acids, and gluconeogenesis. Biotinylation of histone proteins in nuclear chromatin plays a role in chromatin stability and g ...
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CAD (gene)
CAD protein (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase) is a trifunctional multi-domain enzyme involved in the first three steps of pyrimidine biosynthesis. De-novo synthesis starts with cytosolic carbamoylphosphate synthetase II which uses glutamine, carbon dioxide and ATP. This enzyme is inhibited by uridine triphosphate (feedback inhibition). In 2015, the first observed pathological mutations of ''CAD'' were found in a four-year-old boy. CAD protein has been observed in the mid-piece of mammalian spermatozoa, among the mitochondria. Structure CAD protein has a molecular weight of 243 KDa. It is a polypeptide made up of four different domains which make for a multi enzyme unit: Glutaminase (GLN), carbamoyl phosphate synthetase (CPS II), Dihydroorotase (DHO) and aspartate transcarbamoylase (ATC). The protein assembles into ~1.5MDa hexamers. More specifically, the DHO domain assembles into dimers, and ATC domains do so into trimers. The ...
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