Uridine monophosphate 58-97-9

Uridine monophosphate, also known as 5′-uridylic acid and abbreviated UMP, is a nucleotide that is used as a monomer in RNA. It is an ester ofphosphoric acid with the nucleoside uridine. UMP consists of the phosphate group, the pentose sugar ribose, and the nucleobase uracil; hence, it is a ribonucleoside monophosphate. Another common shorthand for the molecule is uridylate - the deprotonated form of the molecule, which is predominant in aqueous solution. As a substituent it takes the form of the prefix uridylyl-.

Identifiers
CAS number 58-97-9 Yes
PubChem 6030
ChemSpider 5808 
MeSH Uridine+monophosphate
Jmol-3D images Image 1
Properties
Molecular formula C9H13N2O9P
Molar mass 324.181
Melting point 202 °C (dec.) [1]
Solubility in water good, also in methanol [1]
Acidity (pKa) 1.0, 6.4, 9.5

Biosynthesis

Uridine monophosphate is formed from Orotidine 5′-monophosphate (orotidylic acid) in a decarboxylation reaction catalyzed by the enzymeorotidylate 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. [2]

In humans, the orotidylate decarboxylase function is carried out by the protein UMP synthase. [3] Defective UMP synthase can result in orotic aciduria, a metabolic disorder.

Effects on animal intelligence

In a study, gerbils fed a combination of uridine monophosphate, choline, and docosahexaenoic acid (DHA) were found to have significantly improved performance in running mazes over those not fed the supplements, implying an increase in cognitive function.[4][5]

Uridine Monophosphate in Foods

In brain research studies such as those mentioned in this article, uridine monophosphate is used as a convenient delivery compound for uridine.Uridine is the active ingredient of the compound. A common misconception is that uridine and its compounds are not available in significant quantities from foods and must be obtained from expensive supplements or prescription drugs. This is not so. Uridine monophosphate is a major component of RNA. Any food rich in RNA, such as Brewer’s yeast or some organ meats, will provide significant quantities of it. For more information, consult the article on uridine.

Uridine diphosphate 58-98-0

Uridine diphosphate, abbreviated UDP, is a nucleoside 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.

Uridine diphosphate
Identifiers
CAS number 58-98-0 Yes
PubChem 1158
ChemSpider 19952429 Yes
MeSH Uridine+diphosphate
ChEMBL CHEMBL130266 
IUPHAR ligand 1749
Properties
Molecular formula C9H14N2O12P2
Molar mass 404.161

Uridine

Uridine, a nucleoside, contains an uracil attached to a ribose ring (known as a ribofuranose) via a β-N1-glycosidic bond.

If uracil is attached to a deoxyribose ring, it is known as a deoxyuridine.

Uridine
Identifiers
CAS number 58-96-8 Yes
UNII WHI7HQ7H85 Yes
DrugBank DB02745
MeSH Uridine
ChEMBL CHEMBL100259 
Jmol-3D images Image 1
Properties
Molecular formula C9H12N2O6
Molar mass 244.2 g mol−1

Dietary sources of uridine

Uridine is one of the four basic components of ribonucleic acid (RNA); the other three are adenosine, guanosine, and cytidine. Upon digestion of foods containing RNA, uridine is released from RNA and is absorbed intact in the gut. Some food sources of uridine are:

  • Sugarcane extract[1]
  • Tomatoes (0.5 to 1.0 g uridine per kilogram dry weight)[2]
  • Brewer’s yeast (3% uridine by dry weight)[3]
  • Beer[4]
  • Broccoli[3]
  • Organ meats (liver, pancreas, etc.)[3]

Consumption of RNA-rich foods may lead to high levels of purines (adenosine and guanosine) in blood. High levels of purines are known to increase uric acid production and may aggravate or lead to conditions such as gout. Moderate consumption of yeast, about 5 grams per day, should provide adequate uridine for improved health with minimal side effects.[citation needed]

Note: It has been suggested that the RNA content of yeast products should be chemically reduced if these products are to be consumed in high amounts (50 grams or more per day) as a source of protein. However, such processing is expensive and, as of 2008, commonly available brewer’s yeast products were not RNA-reduced.[citation needed]

Harvard researchers report that supplementation in rats with a combination of uridine and EPA/DHA omega-3 fatty acids has antidepressant activity.[5]

Uridine in the Glycolysis Pathway

Uridine plays a role in the glycolysis pathway of galactose.[6] There is no catabolic process to metabolize galactose. Therefore, galactose is converted to glucose and metabolized in the common glucose pathway. Once the incoming galactose has been converted into galactose-1-phosphate (Gal-1-P), it is involved in a reaction with UDP-glucose, a glucose molecule bonded to a UDP (uridine-di-phosphate) molecule. This process is catalyzed by the enzyme galactose-1-phosphate uridyl transferase, and transfers the UDP to the galactose molecule. The end result is a UDP-galactose molecule and a glucose-1-phosphate molecule. This process is continued to allow the proper glycolysis of the galactose molecule.

Uramustine 66-75-1

Uramustine (INN) or uracil mustard is a chemotherapy drug which belongs to the class of alkylating agents. It is used in lymphatic malignancies such as non-Hodgkin’s lymphoma. It works by damaging DNA, primarily in cancer cells that preferentially take up the uracil due to their need to make nucleic acids during their rapid cycles of cell division. The DNA damage leads to apoptosis of the affected cells. Bone marrow suppression and nausea are the main side effects.

Chemically it is a derivative of nitrogen mustard and uracil.

Uramustine
Systematic (IUPAC) name
5-[bis(2-chloroethyl)amino]-1H-pyrimidine-2,4-dione
Clinical data
Pregnancy cat.  ?
Legal status  ?
Pharmacokinetic data
Protein binding 5%
Excretion Renal
Identifiers
CAS number 66-75-1 Yes
ATC code None
PubChem CID 6194
DrugBank DB00791
UNII W7KQ46GJ8U 
KEGG D06265 Yes
ChEMBL CHEMBL1488 
Chemical data
Formula C8H11Cl2N3O2 
Mol. mass 252.097 g/mol

Uracil 66-22-8

Uracil (play /ˈjʊərəsɪl/) one of the four nucleobases in the nucleic acid of RNA that are represented by the letters A, G, C and U. The others areadenine, cytosine, and guanine. In RNA, uracil (U) binds to adenine (A) via two hydrogen bonds. In DNA, the uracil nucleobase is replaced bythymine.

Uracil is a common and naturally occurring pyrimidine derivative.[2] Originally discovered in 1900, it was isolated by hydrolysis of yeast nucleinthat was found in bovine thymus and spleen, herring sperm, and wheat germ.[3] It is a planar, unsaturated compound that has the ability to absorb light.[4]

Studies reported in 2008, based on 12C/13C isotopic ratios of organic compounds found in the Murchison meteorite, suggested that uracil,xanthine and related molecules were formed extraterrestrially.[5][6]

In 2012 an analysis of data from the Cassini mission orbiting in the Saturn system showed that Titan’s surface composition may include uracil.

Uracil
Identifiers
CAS number 66-22-8 Yes
UNII 56HH86ZVCT 
ChEMBL CHEMBL566 
RTECS number YQ8650000
Jmol-3D images Image 1
Properties
Molecular formula C4H4N2O2
Molar mass 112.08676 g/mol
Appearance Solid
Density 1.32 g/cm³
Melting point 335 °C[1]
Boiling point N/A – decomposes
Solubility in water Soluble
Hazards
Main hazards carcinogen & teratogen with chronic exposure
NFPA 704
NFPA 704.svg
1
1
0
Flash point non flammable
Related compounds
Related compounds Thymine
Cytosine

Properties

In RNA, uracil base-pairs with adenine and replaces thymine during DNA transcription. Methylation of uracil produces thymine.[8] In DNA, the evolutionary substitution of thymine for uracil may have increased DNA stability and improved the efficiency of DNA replication. Uracil pairs with adenine through hydrogen bonding. When base pairing with adenine, uracil acts as both a hydrogen bond acceptor and a hydrogen bond donor. In RNA, uracil binds with a ribose sugar to form the ribonucleoside uridine. When a phosphate attaches to uridine, uridine 5′-monophosphate is produced.[4]

Uracil undergoes amide-imidic acid tautomeric shifts because any nuclear instability the molecule may have from the lack of formal aromaticityis compensated by the cyclic-amidic stability.[3] The amide tautomer is referred to as the lactam structure, while the imidic acid tautomer is referred to as the lactim structure. These tautomeric forms are predominant at pH 7. The lactam structure is the most common form of uracil.

Uracil tautomers: Amide or lactamstructure (left) and imide or lactimstructure (right)

Uracil also recycles itself to form nucleotides by undergoing a series of phosphoribosyltransferase reactions.[2] Degradation of uracil produces the substrates aspartate, carbon dioxide, and ammonia.[2]

C4H4N2O2 → H3NCH2CH2COO- + NH4+ + CO2

Oxidative degradation of uracil produces urea and maleic acid in the presence of H2O2 and Fe2+ or in the presence of diatomic oxygen and Fe2+.

Uracil is a weak acid. The first site of ionization of uracil is not known.[9] The negative charge is placed on the oxygen anion and produces a pKaof less than or equal to 12. The basic pKa = -3.4, while the acidic pKa = 9.389. In the gas phase, uracil has 4 sites that are more acidic than water.[10]

Synthesis

In a scholarly article published in October 2009, NASA scientists reported having reproduced uracil from pyrimidine by exposing it to ultraviolet light under space-like conditions. This suggests that one possible natural original source for uracil in the RNA world could have beenpanspermia.[11]

There are many laboratory syntheses of uracil available. The first reaction is the simplest of the syntheses, by adding water to cytosine to produce uracil and ammonia.[2] The most common way to synthesize uracil is by the condensation of maleic acid with urea in fuming sulfuric acid[3] as seen below also. Uracil can also be synthesized by a double decomposition of thiouracil in aqueous chloroacetic acid.[3]

C4H5N3O + H2O → C4H4N2O2 + NH3
C4H4O4 + CH4N2O → C4H4N2O2 + 2 H2O + CO

Photodehydrogenation of 5,6-diuracil, which is synthesized by beta-alanine reacting with urea, produces uracil.[12]

Reactions

Uracil readily undergoes regular reactions including oxidation, nitration, and alkylation. While in the presence of phenol (PhOH) and sodium hypochlorite (NaOCl), uracil can be visualized in the blue region of UV light.[3] Uracil also has the capability to react with elemental halogens because of the presence of more than one strongly electron donating group.[3]

Chemical structure of uridine

Uracil readily undergoes addition to ribose sugars and phosphates to partake in synthesis and further reactions in the body. Uracil becomes uridine, uridine monophosphate (UMP), uridine diphosphate (UDP), uridine triphosphate (UTP), and uridine diphosphate glucose (UDP-glucose). Each one of these molecules is synthesized in the body and has specific functions.

When uracil reacts with anhydrous hydrazine, a first-order kinetic reaction occurs and the ring of uracil opens up.[13] If the pH of the reaction increases to >10.5, the uracil anion forms, making the reaction go much slower. The same slowing of the reaction occurs if the pH decreases because of the protonation of the hydrazine.[13] The reactivity of uracil is unchanged even if the temperature changes.[13]

Uses

Uracil can be used for drug delivery and as a pharmaceutical. When elemental fluorine is reacted with uracil, 5-fluorouracil is produced. 5-Fluorouracil is an anticancer drug (antimetabolite) used to masquerade as uracil during the nucleic acid replication process.[2] Because 5-Fluorouracil is similar in shape to, but does not perform the same chemistry as, uracil, the drug inhibits RNA replication enzymes, thereby eliminating RNA synthesis and stopping the growth of cancerous cells.[2] Uracil can also be used in the synthesis of caffeine [14]

Uracil’s use in the body is to help carry out the synthesis of many enzymes necessary for cell function through bonding with riboses and phosphates.[2] Uracil serves as allosteric regulator andcoenzyme for reactions in the human body and in plants.[15] UMP controls the activity of carbamoyl phosphate synthetase and aspartate transcarbamoylase in plants, while UDP and UTP requlate CPSase II activity in animals. UDP-glucose regulates the conversion of glucose to galactose in the liver and other tissues in the process of carbohydrate metabolism.[15] Uracil is also involved in the biosynthesis of polysaccharides and the transportation of sugars containing aldehydes.[15]

It can also increase the risk for cancer in cases in which the body is extremely deficient in folate.[16] The deficiency in folate leads to increased ratio of deoxyuracilmonophosphates(dUMP)/deoxythyminemonophosphates (dTMP) and uracil misincorporation into DNA and eventually low production of DNA.[16]

Uracil can be used to determine microbial contamination of tomatoes. The presence of uracil is an indication of lactic acid bacteria contamination in the fruit.[17] Uracil derivatives containing a diazine ring are used in pesticides.[18] Uracil derivatives are more often used as antiphotosynthetic herbicides, destroying weeds in cotton, sugar beet, turnips, soya, peas,sunflower crops, vineyards, berry plantations, and orchards.[18]

In yeast, uracil concentrations are inversely proportional to uracil permease

Trifluridine 70-00-8

Trifluridine (also called trifluorothymidine or TFT) is an anti-herpesvirus antiviral drug, used primarily on the eye. It was sold under the trade name, Viroptic, by Glaxo Wellcome, now merged into GlaxoSmithKline. The brand is now owned by Monarch Pharmaceuticals, which is wholly owned by King Pharmaceuticals.

It is a nucleoside analogue, a modified form of deoxyuridine, similar enough to be incorporated into viral DNA replication, but the -CF3 group added to the uracil component blocks base pairing.

It is a component of the experimental anti-cancer drug TAS-102.

Trifluridine
Systematic (IUPAC) name
1-[4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5- (trifluoromethyl) pyrimidine-2,4-dione
Clinical data
Trade names Viroptic
AHFS/Drugs.com monograph
Pregnancy cat.  ?
Legal status ℞ Prescription only
Routes Eye drops
Pharmacokinetic data
Half-life 12 minutes
Identifiers
CAS number 70-00-8 Yes
ATC code S01AD02
PubChem CID 6256
DrugBank DB00432
ChemSpider 6020 Yes
UNII RMW9V5RW38 Yes
KEGG D00391 Yes
ChEMBL CHEMBL1129 Yes
Chemical data
Formula C10H11F3N2O5 
Mol. mass 296.2 g/mol

Thymine 65-71-4

Thymine (TThy) is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine,guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nucleobase. As the name suggests, thymine may be derived by methylation of uracil at the 5th carbon. In RNA, thymine is replaced with uracil in most cases. In DNA, thymine (T) binds to adenine (A) via two hydrogen bonds, thus stabilizing the nucleic acid structures.

Thymine combined with deoxyribose creates the nucleoside deoxythymidine, which is synonymous with the term thymidine. Thymidine can be phosphorylated with one, two, or three phosphoric acid groups, creating, respectively, TMP, TDP, or TTP (thymidine mono-, di-, or triphosphate).

One of the common mutations of DNA involves two adjacent thymines or cytosine, which, in presence of ultraviolet light, may form thymine dimers, causing “kinks” in the DNA molecule that inhibit normal function.

Thymine could also be a target for actions of 5-fluorouracil (5-FU) in cancer treatment. 5-FU can be a metabolic analog of thymine (in DNA synthesis) or uracil (in RNA synthesis). Substitution of this analog inhibits DNA synthesis in actively dividing cells.

Thymine bases are frequently oxidized to hydantoins over time after the death of an organism

Thymine
Identifiers
CAS number 65-71-4 Yes
PubChem 1135
ChemSpider 1103 
UNII QR26YLT7LT Yes
MeSH Thymine
ChEMBL CHEMBL993 
Jmol-3D images Image 1
Properties
Molecular formula C5H6N2O2
Molar mass 126.11 g mol−1
Density 1.23 g cm−3(calculated)
Melting point 316-317 °C, 589-590 K, 601-603 °F
Boiling point 335 °C, 608 K, 635 °F (decomposes)

Thymidine 50-89-5

Thymidine (more precisely called deoxythymidine; can also be labelled deoxyribosylthymine, and thymine deoxyriboside) is a chemicalcompound, more precisely a pyrimidine deoxynucleoside. Deoxythymidine is the DNA nucleoside T, which pairs with deoxyadenosine (A) in double-stranded DNA. In cell biology it is used to synchronize the cells in S phase.

Before the boom in thymidine use caused by the need for thymidine for the production of the antiretroviral drug azidothymidine (AZT), much of the world’s thymidine production came from herring sperm.[1] Thymidine occurs almost exclusively in DNA but also occurs in the T-loop of tRNA.

Identifiers
CAS number 50-89-5 Yes
PubChem 1134
UNII VC2W18DGKR 
DrugBank DB04485
MeSH Thymidine
ChEMBL CHEMBL52609 
Jmol-3D images Image 1
Properties
Molecular formula C10H14N2O5
Molar mass 242.23 g mol−1

Structure and properties

In its composition, deoxythymidine is a nucleoside composed of deoxyribose (a pentose sugar) joined to the pyrimidine base thymine.

Deoxythymidine can be phosphorylated with one, two or three phosphoric acid groups, creating respectively dTMP, dTDP or dTTP (deoxythymidine mono- di- or triphosphate).

It exists in solid form as small white crystals or white crystalline powder, has a molecular weight of 242.229 u, and has a melting point of 185 °C. The stability of deoxythymidine under standard temperature and pressure (STP) is very high.

Deoxythymidine is non-toxic and as part of one of the four nucleotides in DNA it is a naturally occurring compound that exists in all living organisms and DNA viruses. RNA has uridine (uracil joined to ribose) instead. Uracil is chemically very similar to thymine, the latter being 5-methyluracil. Since thymine nucleotides are precursors of DNA, not RNA, the prefix “deoxy” is often left out, i.e., deoxythymidine is often just called thymidine.

Thymidine is listed as a chemical teratogen.[2]

Modified analogs of thymidine

Iododeoxyuridine is a radiosensitizer and increases the amount of DNA damage received from ionizing radiation.

Azidothymidine (AZT) – used in the treatment of HIV infection. AZT inhibits the process of reverse transcription, a critical step in the viral life cycle.

Tritiated thymidine is commonly used in cell proliferation assays. The thymidine is incorporated into dividing cells and the level of this incorporation, measured using a liquid scintillation counter, is proportional to the amount of cell proliferation.

Bromodeoxyuridine (BrdU) is another thymidine analog that is often used for the detection of proliferating cells in living tissues.

Edoxudine is an antiviral drug.

Thymectacin 232925-18-7

Thymectacin (NB-1011, NB-101, N-[[5-[(E)-2-Bromovinyl]-2′-deoxyuridin-5′-O-yl](phenoxy)phosphoryl]-L-alanine methyl ester) is an anticancerprodrug of brivudine monophosphate. It developed by New Biotics and it has entered in phase I clinical trials for colon cancer

Thymectacin
Systematic (IUPAC) name
(2S)-methyl 2-((((2R,3S,5R)-5-(5-((E)-2-bromovinyl)-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3-hydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propanoate
Clinical data
Pregnancy cat.  ?
Legal status  ?
Identifiers
CAS number 232925-18-7
ATC code  ?
PubChem CID 6440764
Chemical data
Formula C21H25BrN3O9P 
Mol. mass 574.3185 g/mol

Telbivudine 3424-98-4

Telbivudine is an antiviral drug used in the treatment of hepatitis B infection. It is marketed by Swiss pharmaceutical company Novartis under the trade names Sebivo (Europe) and Tyzeka (United States). Clinical trials have shown it to be significantly more effective than lamivudine oradefovir, and less likely to cause resistance.[1][2][3]

Telbivudine is a synthetic thymidine nucleoside analogue; it is the L-isomer of thymidine. It is taken once daily.

Telbivudine
Systematic (IUPAC) name
1-(2-deoxy-β-L-erythro-pentofuranosyl)-5-methylpyrimidine-2,4(1H,3H)-dione
Clinical data
Trade names Tyzeka
AHFS/Drugs.com monograph
MedlinePlus a607045
Licence data EMA:Link, US FDA:link
Pregnancy cat. (US)
Legal status POM (UK) ℞-only (US)
Routes Oral
Pharmacokinetic data
Protein binding Low (3.3% in vitro)
Metabolism Nil
Half-life 40 to 49 hours (terminal phase)
Excretion Renal
Identifiers
CAS number 3424-98-4 Yes
ATC code J05AF11
PubChem CID 159269
DrugBank DB01265
ChemSpider 140081 Yes
UNII 2OC4HKD3SF Yes
ChEMBL CHEMBL374731 
Synonyms 1-(2-deoxy-β-L-ribofuranosyl)-5-methyluracil
β-L-2-deoxythymidine
β-L-thymidine (LdT)
1-[(2S,4R,5S)-4-hydroxy-5-hydroxymethyltetrahydrofuran-2-yl]-5-methyl-1H-pyrimidine-2,4-dione
Chemical data
Formula C10H14N2O5 
Mol. mass 242.23 g/mol