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Phosphoribosylpyrophosphate
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 ...
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Ribose-phosphate Diphosphokinase
Ribose-phosphate diphosphokinase (or phosphoribosyl pyrophosphate synthetase or ribose-phosphate pyrophosphokinase) is an enzyme that converts ribose 5-phosphate into phosphoribosyl pyrophosphate (PRPP). It is classified under . The enzyme is involved in the synthesis of nucleotides (purines and pyrimidines), cofactors NAD and NADP, and amino acids histidine and tryptophan, linking these biosynthetic processes to the pentose phosphate pathway, from which the substrate ribose 5-phosphate is derived. Ribose 5-phosphate is produced by the HMP Shunt Pathway from Glucose-6-Phosphate. The product phosphoribosyl pyrophosphate acts as an essential component of the purine salvage pathway and the de novo synthesis of purines. Dysfunction of the enzyme would thereby undermine purine metabolism. Ribose-phosphate pyrophosphokinase exists in bacteria, plants, and animals, and there are three isoforms of human ribose-phosphate pyrophosphokinase. In humans, the genes encoding the enzyme are ...
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Uracil Phosphoribosyltransferase
Uracil phosphoribosyltransferase is an enzyme which creates UMP from uracil Uracil () (symbol U or Ura) is one of the four nucleobases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced b ... and phosphoribosylpyrophosphate. This protein may use the morpheein model of allosteric regulation. References External links * * EC 2.4.2 {{2.4-enzyme-stub ...
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Tryptophan
Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α- carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic beta carbon substituent. It is essential in humans, meaning that the body cannot synthesize it and it must be obtained from the diet. Tryptophan is also a precursor to the neurotransmitter serotonin, the hormone melatonin, and vitamin B3. It is encoded by the codon UGG. Like other amino acids, tryptophan is a zwitterion at physiological pH where the amino group is protonated (–; pKa = 9.39) and the carboxylic acid is deprotonated ( –COO−; pKa = 2.38). Humans and many animals cannot synthesize tryptophan: they need to obtain it through their diet, making it an essential amino acid. Function Amino acids, including tryptophan, are used as building blocks in protein biosynthesis, and proteins are required to sustain life. Man ...
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Sugar Phosphates
Sugar phosphates (sugars that have added or substituted phosphate groups) are often used in biological systems to store or transfer energy. They also form the backbone for DNA and RNA. Sugar phosphate backbone geometry is altered in the vicinity of the modified nucleotides. Examples include: * Dihydroxyacetonephosphate * Glucose-6-phosphate * Phytic acid * Teichoic acid Electronic structure of the sugar-phosphate backbone The sugar-phosphate backbone has multiplex electronic structure and the electron delocalisation complicates its theoretical description. Some part of the electronic density is delocalised over the whole backbone and the extent of the delocalisation is affected by backbone conformation due to hyper-conjugation effects. Hyper-conjugation arises from donor-acceptor interactions of localised orbitals in 1,3 positions. Phosphodiesters in DNA and RNA The phosphodiester backbone of DNA and RNA consists of pairs of deoxyribose or ribose sugars linked by phosp ...
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Hypoxanthine
Hypoxanthine is a naturally occurring purine derivative. It is occasionally found as a constituent of nucleic acids, where it is present in the anticodon of tRNA in the form of its nucleoside inosine. It has a tautomer known as 6-hydroxypurine. Hypoxanthine is a necessary additive in certain cells, bacteria, and parasite cultures as a substrate and nitrogen source. For example, it is commonly a required reagent in malaria parasite cultures, since ''Plasmodium falciparum'' requires a source of hypoxanthine for nucleic acid synthesis and energy metabolism. In August 2011, a report, based on NASA studies with meteorites found on Earth, was published suggesting hypoxanthine and related organic molecules, including the DNA and RNA components adenine and guanine, may have been formed extraterrestrially in outer space. The '' Pheretima aspergillum'' worm, used in Chinese medicine preparations, contains hypoxanthine. Reactions It is one of the products of the action of xanthine oxidase ...
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Xanthine Monophosphate
Xanthosine monophosphate also called Xanthylate is an intermediate in purine metabolism. It is a ribonucleoside monophosphate. It is formed from IMP via the action of IMP dehydrogenase, and it forms GMP via the action of GMP synthase. Also, XMP can be released from XTP by enzyme deoxyribonucleoside triphosphate pyrophosphohydrolase containing (d)XTPase activity. It is abbreviated XMP. See also * Xanthosine Xanthosine is a nucleoside derived from xanthine and ribose. It is the biosynthetic precursor to 7-methylxanthosine by the action of 7-methylxanthosine synthase. 7-Methylxanthosine in turn is the precursor to theobromine (active alkaloid in cho ... References Further reading * * Nucleotides Xanthines {{Biochem-stub ...
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Xanthine
Xanthine ( or ; archaically xanthic acid; systematic name 3,7-dihydropurine-2,6-dione) is a purine base (genetics), base found in most human body tissues and fluids, as well as in other organisms. Several stimulants are derived from xanthine, including caffeine, theophylline, and theobromine. Xanthine is a product on the pathway of purine degradation. * It is created from guanine by guanine deaminase. * It is created from hypoxanthine by xanthine oxidoreductase. * It is also created from xanthosine by purine nucleoside phosphorylase. Xanthine is subsequently converted to uric acid by the action of the xanthine oxidase enzyme. Use and manufacturing Xanthine is used as a drug precursor (chemistry), precursor for human and animal medications, and is manufactured as a pesticide ingredient. Clinical significance Derivatives of xanthine (known collectively as xanthines) are a group of alkaloids commonly used for their effects as mild stimulants and as bronchodilators, notably in the t ...
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Xanthine Phosphoribosyltransferase
In enzymology, a xanthine phosphoribosyltransferase () is an enzyme that catalyzes the chemical reaction :XMP + diphosphate \rightleftharpoons 5-phospho-alpha-D-ribose 1-diphosphate + xanthine Thus, the two substrates of this enzyme are XMP and diphosphate, whereas its two products are 5-phospho-alpha-D-ribose 1-diphosphate and xanthine. This enzyme belongs to the family of glycosyltransferases, specifically the pentosyltransferases. The systematic name of this enzyme class is XMP:diphosphate 5-phospho-alpha-D-ribosyltransferase. Other names in common use include Xan phosphoribosyltransferase, xanthosine 5'-phosphate pyrophosphorylase, xanthylate pyrophosphorylase, xanthylic pyrophosphorylase, XMP pyrophosphorylase, 5-phospho-alpha-D-ribose-1-diphosphate:xanthine, phospho-D-ribosyltransferase, 9-(5-phospho-beta-D-ribosyl)xanthine:diphosphate, and 5-phospho-alpha-D-ribosyltransferase. This enzyme participates in purine metabolism. Structural studies As of late 2007, 6 stru ...
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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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Uracil
Uracil () (symbol U or Ura) is one of the four nucleobases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by thymine (T). Uracil is a demethylated form of thymine. Uracil is a common and naturally occurring pyrimidine derivative. The name "uracil" was coined in 1885 by the German chemist Robert Behrend, who was attempting to synthesize derivatives of uric acid. Originally discovered in 1900 by Alberto Ascoli, it was isolated by hydrolysis of yeast nuclein; it was also found in bovine thymus and spleen, herring sperm, and wheat germ. It is a planar, unsaturated compound that has the ability to absorb light. Based on 12C/13C isotopic ratios of organic compounds found in the Murchison meteorite, it is believed that uracil, xanthine, and related molecules can also be formed extraterrestrially. Data from the Cassini mission, orbiting in the Saturn ...
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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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Orotate
Orotic acid is a pyrimidinedione and a carboxylic acid. Historically, it was believed to be part of the vitamin B complex and was called vitamin B13, but it is now known that it is not a vitamin. The compound is synthesized in the body via a mitochondrial enzyme, dihydroorotate dehydrogenase or a cytoplasmic enzyme of pyrimidine synthesis pathway. It is sometimes used as a mineral carrier in some dietary supplements (to increase their bioavailability), most commonly for lithium orotate. Synthesis Dihydroorotate is synthesized to orotic acid by the enzyme dihydroorotate dehydrogenase, where it later combines with phosphoribosyl pyrophosphate (PRPP) to form orotidine-5'-monophosphate (OMP). A distinguishing characteristic of pyrimidine synthesis is that the pyrimidine ring is fully synthesized before being attached to the ribose sugar, whereas purine synthesis happens by building the base directly on the sugar. Chemistry Orotic acid is a Bronsted acid and the anion (oro ...
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