A triazine nucleoside used as an antineoplastic antimetabolite. It interferes with pyrimidine biosynthesis thereby preventing formation of cellular nucleic acids. As the triacetate, it is also effective as an antipsoriatic.
Orotidine-5'-phosphate carboxy-lyase. Catalyzes the decarboxylation of orotidylic acid to yield uridylic acid in the final step of the pyrimidine nucleotide biosynthesis pathway. EC 4.1.1.23.
The enzyme catalyzing the formation of orotidine-5'-phosphoric acid (orotidylic acid) from orotic acid and 5-phosphoribosyl-1-pyrophosphate in the course of pyrimidine nucleotide biosynthesis. EC 2.4.2.10.
An enzyme that in the course of pyrimidine biosynthesis, catalyzes the oxidation of dihydro-orotic acid to orotic acid utilizing oxygen as the electron acceptor. This enzyme is a flavoprotein which contains both FLAVIN-ADENINE DINUCLEOTIDE and FLAVIN MONONUCLEOTIDE as well as iron-sulfur centers. EC 1.3.3.1.
The monoanhydride of carbamic acid with PHOSPHORIC ACID. It is an important intermediate metabolite and is synthesized enzymatically by CARBAMYL-PHOSPHATE SYNTHASE (AMMONIA) and CARBAMOYL-PHOSPHATE SYNTHASE (GLUTAMINE-HYDROLYZING).
Uridine 5'-(tetrahydrogen triphosphate). A uracil nucleotide containing three phosphate groups esterified to the sugar moiety.
5'-Uridylic acid. A uracil nucleotide containing one phosphate group esterified to the sugar moiety in the 2', 3' or 5' position.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
A family of anaerobic, coccoid to rod-shaped METHANOBACTERIALES. Cell membranes are composed mainly of polyisoprenoid hydrocarbons ether-linked to glycerol. Its organisms are found in anaerobic habitats throughout nature.
Inorganic salts or organic esters of phosphorous acid that contain the (3-)PO3 radical. (From Grant & Hackh's Chemical Dictionary, 5th ed)
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
Shortened forms of written words or phrases used for brevity.
Lists of words, usually in alphabetical order, giving information about form, pronunciation, etymology, grammar, and meaning.
Detailed account or statement or formal record of data resulting from empirical inquiry.
A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.
The portion of an interactive computer program that issues messages to and receives commands from a user.
Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.
Sequential operating programs and data which instruct the functioning of a digital computer.
The addition of descriptive information about the function or structure of a molecular sequence to its MOLECULAR SEQUENCE DATA record.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A cluster of metabolic risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome X include excess ABDOMINAL FAT; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state. (from AHA/NHLBI/ADA Conference Proceedings, Circulation 2004; 109:551-556)
Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.
RNA that has catalytic activity. The catalytic RNA sequence folds to form a complex surface that can function as an enzyme in reactions with itself and other molecules. It may function even in the absence of protein. There are numerous examples of RNA species that are acted upon by catalytic RNA, however the scope of this enzyme class is not limited to a particular type of substrate.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Proteins prepared by recombinant DNA technology.
Colloids formed by the combination of two immiscible liquids such as oil and water. Lipid-in-water emulsions are usually liquid, like milk or lotion. Water-in-lipid emulsions tend to be creams. The formation of emulsions may be aided by amphiphatic molecules that surround one component of the system to form MICELLES.
Unctuous combustible substances that are liquid or easily liquefiable on warming, and are soluble in ether but insoluble in water. Such substances, depending on their origin, are classified as animal, mineral, or vegetable oils. Depending on their behavior on heating, they are volatile or fixed. (Dorland, 28th ed)
A genus of mushrooms in the family Tricholomataceae, whose species are characterized by a slimy cap (FRUITING BODIES, FUNGAL).
Exclusive legal rights or privileges applied to inventions, plants, etc.
Agents that modify interfacial tension of water; usually substances that have one lipophilic and one hydrophilic group in the molecule; includes soaps, detergents, emulsifiers, dispersing and wetting agents, and several groups of antiseptics.
The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
A clear, odorless, tasteless liquid that is essential for most animal and plant life and is an excellent solvent for many substances. The chemical formula is hydrogen oxide (H2O). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Agents that arrest cells in MITOSIS, most notably TUBULIN MODULATORS.
Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.
A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from SPERM FLAGELLUM; CILIA; and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to COLCHICINE; VINCRISTINE; and VINBLASTINE.
A condition in which the FORAMEN OVALE in the ATRIAL SEPTUM fails to close shortly after birth. This results in abnormal communications between the two upper chambers of the heart. An isolated patent ovale foramen without other structural heart defects is usually of no hemodynamic significance.
A cell line derived from cultured tumor cells.
A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as AMMONIUM HYDROXIDE.
An enzyme that catalyzes the formation of carbamoyl phosphate from ATP, carbon dioxide, and glutamine. This enzyme is important in the de novo biosynthesis of pyrimidines. EC 6.3.5.5.
An enzyme that catalyzes the formation of carbamoyl phosphate from ATP, carbon dioxide, and ammonia. This enzyme is specific for arginine biosynthesis or the urea cycle. Absence or lack of this enzyme may cause CARBAMOYL-PHOSPHATE SYNTHASE I DEFICIENCY DISEASE. EC 6.3.4.16.

Paramyxovirus-avian cell relationship: discrepant impact of 6-azauridine on virus production by susceptible and less susceptible cells. (1/19)

The replication of mumps virus in susceptible chicken embryonic heart cells was escalated by daily treatment of cultures with 6-azauridine (6-AU). On the other hand, virus production by less susceptible liver cells was depressed by 6-AU. The population of infected susceptible cells was not increased, but the release of virus by infected susceptible cells was enhanced 20-fold by 10 mug of 6-AU per ml. Less susceptible cells, which incorporated less ribonucleic acid and protein precursor than susceptible cells, sustained a constant level of viral release during 6-AU treatment; however, the number of infected less susceptible cells underwent substantial decline.  (+info)

Mechanisms of action of 6-thioguanine, 6-mercaptopurine, and 8-azaguanine. (2/19)

The effects of 6-thioguanine on purine biosynthesis and cell viability have been examined in H.Ep. 2 cells grown in culture. Toxicity is not reversed by aminoimidazolecarboxamide, suggesting that inhibition of purine biosynthesis de novo is not the sole mechanism of toxicity. Also, 6-(methylmercapto)purine ribonucleoside, a potent inhibitor of purine biosynthesis de novo, produces more marked reductions in cellular pools of purines than does 6-thioguanine without killing cells. There is no apparent inhibition by 6-thioguanosine 5'-monophosphate of other enzymes leading to the synthesis of guanosine 5'-triphosphate as determined in whole cells by measurements of radioactive hypoxanthine or guanine incorporation. Inhibition of DNA synthesis by 1 mM thymidine protects cells from 6-mercaptopurine or 6-thioguanine but fails to protect cells from 8-azaguanine toxicity. On the other hand, inhibition of RNA synthesis by 6-azauridine plus deoxycytidine protects cells against 8-azaguanine but does not protect against 6-thioguanine or 6-mercaptopurine toxicity. In agreement with the in vitro data, arabinosylcytosine (a potent inhibitor of DNA synthesis) fails to protect mice against 8-azaguanine but has previously been shown to protect mice from 6-mercaptopurine or 6-thioguanine toxicity. The results support the hypotheses of others that incorporation into DNA (as 6-thioguanine nucleotide) is a mechanism of toxicity for these thiopurines, whereas 8-azaguanine is toxic due to its incorporation into RNA.  (+info)

Inhibition of human coronavirus NL63 infection at early stages of the replication cycle. (3/19)

Human coronavirus NL63 (HCoV-NL63), a recently discovered member of the Coronaviridae family, has spread worldwide and is associated with acute respiratory illness in young children and elderly and immunocompromised persons. Further analysis of HCoV-NL63 pathogenicity seems warranted, in particular because the virus uses the same cellular receptor as severe acute respiratory syndrome-associated coronavirus. As there is currently no HCoV-NL63-specific and effective vaccine or drug therapy available, we evaluated several existing antiviral drugs and new synthetic compounds as inhibitors of HCoV-NL63, targeting multiple stages of the replication cycle. Of the 28 compounds that we tested, 6 potently inhibited HCoV-NL63 at early steps of the replication cycle. Intravenous immunoglobulins, heptad repeat 2 peptide, small interfering RNA1 (siRNA1), siRNA2, beta-D-N(4)-hydroxycytidine, and 6-azauridine showed 50% inhibitory concentrations of 125 microg/ml, 2 microM, 5 nM, 3 nM, 400 nM, and 32 nM, respectively, and low 50% cytotoxicity concentrations (>10 mg/ml, >40 microM, >200 nM, >200 nM, >100 microM, and 80 microM, respectively). These agents may be investigated further for the treatment of coronavirus infections.  (+info)

Uridine triphosphate deficiency, growth inhibition, and death in ascites hepatoma cells induced by a combination of pyrimidine biosynthesis inhibition with uridylate trapping. (4/19)

A selective deficiency of uridine triphosphate (UTP) was induced in AS-30D rat ascites hepatoma cells by the synergistic action of D-galactosamine and 6-azauridine. The resistance of these hepatoma cells to low concentrations of D-galactosamine (less than 2 mM) was due to their active de novo pyrimidine synthesis which compensated the trapping of uridylate in the form of uridine diphosphate-amino sugars derived from D-galactosamine. The additional blockage of de novo pyrimidine synthesis led to noncompensated uridylate trapping with a UTP content of less than 0.05 mmole/kg of cell wet weight as compared to the control level of 0.66 mmole/kg. The induction of UTP deficiency by incubating the cells with low concentrations of D-galactosamine and 6-azauridine (0.5 mM each) was not accompanied by significant changes in the content of adenine and guanine nucleotides, uridine diphosphate glucose, and uridine diphosphate galactose. The depletion of UTP pools could be reversed within 10 min by the addition of uridine; orotate or uracil were completely ineffective in these hepatoma cells. A UTP content in the range of 0.1 to 0.4 mmole/kg, induced by either 6-azauridine or D-galactosamine, was associated with a reversible depression of cell growth in suspension culture. A UTP content below 0.05 mmole/kg led to irreversible growth inhibition and to necrocytosis in culture, as well as to a loss of transplantability in vivo. Uridine reversal studies indicated that the percentage of cells able to resume growth in culture decreased with an increasing time period of UTP deficiency. The deficiency period required for irreparable or lethal damage in these hepatoma cells ranged from 3 to 20 hr. The principle of noncompensated uridylate trapping can be extended to other inhibitors of nucleotide synthesis combined with various nucleotide-trapping sugar analogs. Noncompensated nucleotide trapping may be useful for an induction of selective nucleotide deficiencies in tumor cells.  (+info)

Coordinate overproduction of orotate phosphoribosyltransferase and orotidine-5'-phosphate decarboxylase in hamster cells resistant to pyrazofurin and 6-azauridine. (5/19)

Cells resistant to pyrazofurin and 6-azauridine have been selected from a simian virus 40-transformed Syrian hamster line and from a Chinese hamster lung line. By increasing the concentrations of inhibitors in several steps, mutant cells from both lines have been obtained which resist high concentrations (1 to 5 mM) of the two inhibitors separately or together. Orotidine-5'-phosphate decarboxylase (EC 4.1.1.23), the sixth and last enzyme in UMP biosynthesis, is inhibited by the nucleoside monophosphates derived from pyrazofurin or 6-azauridine. The activity of this enzyme is increased in each resistant cell line tested. Furthermore, there is a parallel increase in each case in the activity of the fifth enzyme of the pathway, orotate phosphoribosyltransferase (EC 2.4.2.10), which is not inhibited by pyrazofurin or 6-azauridine monophosphates, and the amount of increase is up to 67 times the level found in wild type cells. In contrast, the activities of the first three enzymes of UMP biosynthesis remain essentially unchanged in the mutants. Resistant Chinese hamster cells remain sensitive to 5-fluorouridine; this indicates that uridine kinase, the enzyme necessary to convert 6-azauridine to the monophosphate, is still functional.  (+info)

Identification of 6-azauridine triphosphate in L1210 cells and its possible relevance to cytotoxicity. (6/19)

L1210 cells treated with 1 mM 6-azauridine (AzUrd) (concentration causing 50% inhibition of cell growth, 3 microM) continued to divide at a reduced rate for 72 h before stopping. However, a 24-h treatment was lethal to 99% of the cells, as determined by colony formation. To investigate the mechanism for this delayed cytotoxicity, the metabolism of AzUrd was studied. Cells incubated with AzUrd contained a new 254 nm-absorbing component, not found in control cells. It appeared to be 6-azauridine-5'-triphosphate, since it was the only peak in the triphosphate region of the chromatogram which contained 3H after incubation of cells with [3H]AzUrd. Incorporation of [3H]AzUrd into the acid-insoluble fraction (nucleic acids) was also detected. A role for this incorporation in the mechanism of AzUrd cytotoxicity was strongly suggested by the observation that cordycepin (0.01 mM) partially protected cells from the lethality of AzUrd, presumably by preventing its incorporation into RNA. The previously known inhibition of pyrimidine de novo synthesis by AzUrd was confirmed by a decrease in the intracellular contents of UTP and CTP in AzUrd-treated cells. Therefore, we propose that the inhibition of pyrimidine de novo synthesis and the incorporation into nucleic acid(s) may act in concert to produce the cytotoxic effects of AzUrd.  (+info)

Orotic aciduria fibroblasts express a labile form of UMP synthase. (7/19)

Orotic aciduria (type 1) results from a mutation in the gene for UMP synthase, a bifunctional protein containing the two enzyme activities which convert orotic acid and 5-phosphoribosyl-1-pyrophosphate to UMP and CO2. In fibroblasts from individuals with orotic aciduria, these two enzymatic activities are about 1% of normal but increase dramatically when deficient cells are grown in the presence of 6-azauridine. Using a polyclonal antiserum to sodium dodecyl sulfate-denatured, pure human UMP synthase, we show that fibroblasts from a patient with orotic aciduria have a low level of immunoreactive UMP synthase protein. Pulse-chase analysis reveals that the UMP synthase is degraded rapidly in the deficient cells. Growth of deficient cells in 6-azauridine leads to an increase in UMP synthase protein and its two enzymatic activities via a decreased rate of proteolytic degradation of UMP synthase. UMP synthase in extracts from deficient cells is more readily denatured by heat and is stabilized after growth of cells in 6-azauridine. These data suggest that the detrimental deficiency of this one patient results from a structurally altered UMP synthase that is probably present in low steady-state amounts due to proteolysis and that this labile protein can be stabilized against heat denaturation and proteolytic degradation by 6-aza-UMP.  (+info)

Effect of 6-azauridine on de novo pyrimidine biosynthesis in cultured Ehrlich ascites cells. Orotate inhibition of dihydroorotase and dihydroorotate dehydrogenase. (8/19)

The inhibition of dihydro-orotase (E 3.5.2.3) and dihydroorotate (DHO) dehydrogenase (dihydro-orotate oxidase, EC 1.3.3.1) by cellular orotate (OA) in Ehrlich ascites cells was studied by measuring the accumulation of the intermediates of de novo pyrimidine biosynthesis at various times after the addition of 6-azauridine to the culture medium. The addition of 6-azauridine resulted in the accumulation of orotidine, OA, DHO, and carbamyl aspartate (CAA). The use of the observed ratios of [CCA]/[OA] and [DHO]/[OA] and other known constants allowed us to calculate that the increased cellular OA concentration caused primarily an inhibition of DHO dehydrogenase rather than an inhibition of dihydroorotase. A constant ratio of [CAA]/[DHO] was observed which probably indicates that the interconversion of these two intermediates catalyzed by dihydroorotase is near equilibrium in these cells as has been observed in vitro (Christopherson, R.I., Matsuura, T., and Jones, M.E. (1978) Anal. Biochem. 89, 225-234). It is suggested that the probable intracellular accumulation of CAA in patients with oroticaciduria may have significant secondary effects.  (+info)

Looking for online definition of 6-Azauridine or what 6-Azauridine stands for? 6-Azauridine is listed in the Worlds largest and most authoritative dictionary database of abbreviations and acronyms
TY - JOUR. T1 - Leflunomide Reduces Proliferation and Induces Apoptosis in Neuroblastoma Cells In Vitro and In Vivo. AU - Zhu, Shunqin. AU - Yan, Xiaomin. AU - Xiang, Zhonghuai. AU - Ding, Han Fei. AU - Cui, Hongjuan. PY - 2013/8/9. Y1 - 2013/8/9. N2 - Leflunomide as an immunosuppressive drug is generally used in the treatment of rheumatoid arthritis. It inhibits DHODH (dihydroorotate dehydrogenase), which is one of the essential enzymes in the de novo pyrimidine biosynthetic pathway. Here we showed that leflunomide significantly reduced cell proliferation and self-renewal activity. Annexin V-FITC/PI staining assay revealed that leflunomide induced S-phase cell cycle arrest, and promoted cell apoptosis. In vivo xenograft study in SCID mice showed that leflunomide inhibited tumor growth and development. We also observed that DHODH was commonly expressed in neuroblastoma. When treated with leflunomide, the neuroblastoma cell lines BE(2)-C, SK-N-DZ, and SK-N-F1 showed dramatic inhibition of DHODH ...
Dagg, C P. and Coggin, C, Combined effects of a mutant gene, paddlefoot, and a teratogen, 6-azauridine, on limb development of mouse embryos. Abstr. (1976). Subject Strain Bibliography 1976. 174 ...
Cannabinoid receptor subtype 2 (CB2) has been shown to be up-regulated in activated microglia and therefore plays an important role in neuroinflammatory and neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis and Alzheimers disease. The CB2 receptor is therefore considered as a very promising target for therapeutic approaches as well as for imaging. A promising 2-oxoquinoline derivative designated KP23 was synthesized and radiolabeled and its potential as a ligand for PET imaging the CB2 receptor was evaluated. [11C]KP23 was obtained in 10%-25% radiochemical yield (decay corrected) and 99% radiochemical purity. It showed high stability in phosphate buffer, rat and mouse plasma. In vitro autoradiography of rat and mouse spleen slices, as spleen expresses a high physiological expression of CB2 receptors, demonstrated that [11C]KP23 exhibits specific binding towards CB2. High spleen uptake of [11C]KP23 was observed in dynamic in vivo PET studies with Wistar rats. In
Tiopronin - Get up-to-date information on Tiopronin side effects, uses, dosage, overdose, pregnancy, alcohol and more. Learn more about Tiopronin
Welcome to Sonus Hearing Care Professionals, where our goal is to help you with a variety of hearing needs. For over 20 years, weve served residents in San Diego with hearing aids, tinnitus management, assistive listening devices, and more. Our office focuses on providing quality care with a compassionate touch. We honor the needs and priorities of each individual because we understand that hearing is not a one size fits all approach. Sonus Hearing Care Professionals accepts 95% of popular insurance plans and is here to help with your hearing needs.. ...
MetabolismPurines, pyrimidines, nucleosides, and nucleotidesPyrimidine ribonucleotide biosynthesisorotidine 5-phosphate decarboxylase (TIGR01740; EC 4.1.1.23; HMM-score: 207.2) ...
Phosphorylates uridine and cytidine to uridine monophosphate and cytidine monophosphate. Does not phosphorylate deoxyribonucleosides or purine ribonucleosides. Can use ATP or GTP as a phosphate donor. Can also phosphorylate cytidine and uridine nucleoside analogs such as 6-azauridine, 5-fluorouridine, 4-thiouridine, 5-bromouridine, N(4)-acetylcytidine, N(4)-benzoylcytidine, 5-fluorocytidine, 2-thiocytidine, 5-methylcytidine, and N(4)-anisoylcytidine.
When I read her response, she said she found the humor in the video, that she laughed, but then she started to cry and that touched me, said Rodriguez.. His viral video brought to life an insecurity that Kelsey had lived with for years. She hardly smiled. Her teeth were rotting, broken, and in some cases missing.. It had been four years to the day, since I had posted a picture when I was smiling, said Schmidt.. The Clear Lake dentist wanted her to smile again, so together with dental technician Ron Wilson, they offered to fix her decaying smile for free.. This was a special case, said Wilson.. After multiple x-rays and tests, it was finally the big day.. Dr. Rodriguez extracted 28 teeth during two surgeries, before showing Kelsey the smile shed wished for for years. Her prayers had been answered.. I was so excited that first night, I couldnt sleep, said Schmidt. I sat up and took four years worth of selfies, Im not too embarrassed to admit it. ...
Relevant Papers 1. Yablonski, M. J., Pasek, D. A., Han, B.-D., Jones, M. E., & Traut, T. W. (1996) Intrinsic activity and stability of bifunctional UMP synthase, and of its two separate domains, orotate phosphoribosyl-transferase and orotidine-5-phosphate decarboxylase. J. Biol. Chem.271, 10704-10708. 2. Traut, T.W. (1994) Dissociation of enzyme oligomers: A mechanism for allosteric regulation. CRC Crit. Rev. Biochem. Mol. Biol.29, 125-163. 3. Matthews, M.M., Liao, W., Kvalnes-Krick, K.L., and Traut, T.W. (1992) Beta-alanine Synthase: Purification and allosteric properties. Arch. Biochem. Biophys. 293, 254-263. ...
Several hits in gapped BLAST to uridine kinase sequences, e.g. residues 4-206 are 41% similar to the enzyme from B.subtilis (Z99117). UU332 is similar to MG382 and, weakly, to TP0667, two predicted uridine kinases. No similarity to C.trachomatis ...
Patient with orotic aciduria may present with symptoms and signs such as neurological disorders, failure to thrive, anemia, pallor, weakness and lethargy. Orotic aciduria may lead to accumulation of orotic acid which impair the synthesis of nuclei acid
1DQW: Anatomy of a proficient enzyme: the structure of orotidine 5-monophosphate decarboxylase in the presence and absence of a potential transition state analog.
human being malaria parasite is endemic in 87 countries putting 2. choices to fight drug-resistant parasites (4). Nevertheless latest reports with the Globe Health Organization claim that level of resistance to artemisinin is certainly developing across the Thai-Cambodian boundary underscoring the necessity to get a continual pipeline of brand-new drug advancement to fight this disease. The malaria parasite depends solely on de novo pyrimidine biosynthesis to provide precursors for DNA and RNA biosynthesis (5 6 On the other GATA2 hand the individual host cells support the enzymatic equipment for both de novo pyrimidine biosynthesis as well as for salvage of preformed pyrimidine bases and nucleosides. Having less a redundant system to obtain pyrimidines in malaria has raised interest in this pathway as a potential source for new therapeutic targets. Dihydroorotate dehydrogenase (DHODH)4 is a flavin mononucleotide (FMN)-dependent mitochondrial enzyme that catalyzes the oxidation of dihydroorotate ...
TY - JOUR. T1 - Motional dynamics of the catalytic loop in OMP synthase. AU - Wang, Gary P.. AU - Cahill, Sean M.. AU - Liu, Xiaohong. AU - Girvin, Mark E.. AU - Grubmeyer, Charles. PY - 1999/1/5. Y1 - 1999/1/5. N2 - In de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase catalyzes the formation of orotidine 5-monophosphate (OMP) from orotic acid and α-D-5-phosphoribosyl-1-pyrophosphate (PRPP). The known three- dimensional structure of the dimeric enzyme from Salmonella typhimurium is similar to that of other Type I phosphoribosyltransferases (nucleotide synthases) with a solvent-exposed active site atop a Rossman-type nucleotide binding fold. The three-dimensional structure of an enzyme - inhibitor complex [Henriksen et al. (1996) Biochemistry 35, 3803-3809] indicates that of the two identical solvent-exposed loops can descend to cover the active site of the adjacent subunit of the dimeric enzyme. Catalytically essential residues are known to reside on this loop. In the present ...
New treatments need to be developed for the significant human diseases of toxoplasmosis and malaria to circumvent problems with current treatments and drug resistance. Apicomplexan parasites causing these lethal diseases are deficient in pyrimidine salvage, suggesting that selective inhibition of de novo pyrimidine biosynthesis can lead to a severe loss of uridine 5-monophosphate (UMP) and thymidine 5-monophosphate (dTMP) pools, thereby inhibiting parasite RNA and DNA synthesis. Disruption of Toxoplasma gondii carbamoyl phosphate synthetase II (CPSII) induces a severe uracil auxotrophy with no detectable parasite replication in vitro and complete attenuation of virulence in mice. Here we show that a CPSII cDNA minigene efficiently complements the uracil auxotrophy of CPSII-deficient mutants, restoring parasite growth and virulence. Our complementation assays reveal that engineered mutations within, or proximal to, the catalytic triad of the N-terminal glutamine amidotransferase (GATase) domain ...
Thus, the two substrates of this enzyme are ATP and uridine, whereas its two products are ADP and UMP. This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing groups (phosphotransferases) with an alcohol group as acceptor. The systematic name of this enzyme class is ATP:uridine 5-phosphotransferase. Other names in common use include pyrimidine ribonucleoside kinase, uridine-cytidine kinase, uridine kinase (phosphorylating), and uridine phosphokinase. This enzyme participates in pyrimidine metabolism. ...
I was planning on taking a small break from blogging after the #CAN2013 shebang, but this study is just too sweet to pass on. Serotonin! Sexual preference! Lesbian mice! From my Alma Matar! Interested? Read on.
The DHODH, or dihydroorotate dehydrogenase, gene encodes a 43-kDa enzymatic protein localized to the inner mitochondrial membrane, where it interacts with the mitochondrial respiratory chain and acts as a rate-limiting step in de novo pyrimidine biosynthesis (51-53). Mutations within DHODH have been linked with Miller Syndrome, a recessive disorder characterized by malformations of the limbs and eyes, among other symptoms (54-57). DHODH has also been investigated for a role in cancer, including melanoma (58) and acute myeloid leukemia (59), and decreased expression of DHODH was associated with breast cancer risk (60). Several other studies have examined the utility of DHODH inhibitors in cancer by inducing cell-cycle arrest and apoptosis in cancer cells (59, 61-66). Although DHODH has not been previously associated with lung cancer risk, the abundance of biological evidence for its pleiotropic role in cancer gives credibility to the association.. We identified significant associations on ...
|h4 style=font-family: arial; color: navy;||font size=3|Potassium Orotate - a supplement with a talent for reversing tissue damage throughout the body, including the brain|/font||/h4||p style=font-family: arial;||font size=3|Potassium orotate is a mineral salt that is normally found in small amounts in all living things. Each molecule of potassium orotate consists of a molecule of orotic acid in which one of the hydrogen atoms is replaced by a potassium atom. |/font||/p| |p style=font-family: arial;||font size=3|Orotate (orotic acid) is a biochemical substance made by all living cells. It is a necessary raw material for making the genetic material: RNA and DNA.|/font||/p| |p style=font-family: arial;||font size=3|Potassium is an essential mineral throughout the biological world, and is the most prevalent positive-charged ion in animal cells. This element helps to regulate the amounts of water and electrolytes in cells and plays an
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(EMAILWIRE.COM, March 27, 2019 ) World population is continuously growing, and so is water consumption. It is estimated that 2 billion to 3 billion people will be living in water stress areas by 2025. Demand for fresh water is rapidly increasing throughout the world. Climate change and depleting...
1-Hydroxyquinolones were recently described as effective inhibitors of Toxoplasma gondii replication. These compounds (e.g. HDQ and compound B) were previously shown to inhibit the alternative NADH dehydrogenase (NADH2-I) activity and thus the respiratory chain of T. gondii. However, the phenotype of ndh2-I knock-out mutants suggested the presence of additional target(s). In this study, the fourth enzyme of de novo pyrimidine biosynthesis, the T. gondii dihydroorotate dehydrogenase (TgDHODH), was identified as a novel 1-hydroxyquinolone target. T. gondii mutants with a partial resistance phenotype towards 1-hydroxyquinolones were used to analyze the expression profile and the coding sequence of all ubiquinone reducing mitochondrial dehydrogenases, which are the likely targets of 1-hydroxyquinolones. Quantitative RT-PCR analysis revealed no significant differences in the mRNA expression level of these enzymes. However, DNA-sequencing identified a single point mutation in codon 302 of the TgDHODH ...
Candidate: Brequinar. Type: Orally available, potent, and selective small molecule dihydroorotate dehydrogenase (DHODH) inhibitor designed to block host cell de novo pyrimidine biosynthesis.. Status: Clear Creek said September 1 it received FDA clearance on an IND application to study its lead drug candidate brequinar as a COVID-19 treatment, and has dosed the first patient in the Phase Ia CRISIS trial (NCT04425252).. The randomized, open label, multi-center study will enroll up to 24 patients hospitalized with COVID-19, with the aim of assessing the preliminary efficacy, safety, and tolerability of brequinar. The study will assign participants 1:2 to standard of care or standard of care plus five once-daily oral doses of 100 mg brequinar. The primary endpoint is safety/tolerability measured by rates of post randomization adverse events and hematology/chemistry safety labs. The trial was recruiting at four sites in Hartford, CT; Jacksonville, FL; Philadelphia; and Tampa, FL.. Clear Creek cited ...
Blair, D G. and Rainnie, D J., Specific activities of uridine kinase and uridine phosphorylase of ehrlich ascites carcinoma cells during tumor growth. Abstr. (1969). Subject Strain Bibliography 1969. 23 ...
The experiments described here reveal the existence of three serendipitous pathways that allow synthesis of PLP in the ΔpdxB strain when any one of seven different genes is overexpressed. The number of genes that allow complementation is surprising; most multicopy suppression experiments reveal fewer genes that can complement a strain lacking a metabolic enzyme. For example, Patrick et al (2007) found that 21 of 104 knockout strains of E. coli could be complemented by multicopy suppression using the ASKA library, but in most cases by only one or two genes. One exception, the ΔglyA strain, was complemented by four genes, one of which encodes an antisigma factor. A second unusual case was described by Miller and Raines (2004, 2005), who found that overexpression of four genes encoding glycokinases with promiscuous glucokinase activity complemented a strain lacking glucokinase. Our finding that seven different genes complement the ΔpdxB strain is, to our knowledge, the record. Furthermore, our ...
Alfa Aesar™ 5-Fluorouridine, 97% 1g Alfa Aesar™ 5-Fluorouridine, 97% Fluorotrifluoromethylbenzy to Fmocn -Organics
(KudoZ) Italian to English translation of cromo orotato, carbossimetilcellulosa: 1. chromium orotate 2. carboxyl methylcellulose [Medical].
Lithium plays a role in the regulation of neurotransmitter activity, gene expression, and nerve cell health. Buy Bio-Innovations Lithium Orotate 5 mg.
... (triacetyl-6-azauridine) is a drug which was developed for the treatment of psoriasis, and also has anti-cancer and ... It is a prodrug which is metabolised to the nucleoside analogue 6-azauridine in the body. Azaribine was approved for clinical ... Elis J, Rasková H (March 1972). "New indications for 6-azauridine treatment in man. A review". European Journal of Clinical ... triacetyl-6-azauridine". Cancer Research. 23: 444-53. PMID 14023746. Morrey JD, Smee DF, Sidwell RW, Tseng C (July 2002). " ...
Large amounts of orotidine are excreted in the urine of cancer patients treated with 6-azauridine. The symbol commonly used for ...
Examples of successfully phosphorylated substrates include 6-azauridine, 5-azacytidine, 4-thiouridine, 5-fluorocytidine, and 5- ...
Sanders, M. A., Wiesner, B. P. and Yudkin, J. 'Control of Fertility by 6-Azauridine' McLaren, A., Reproduction by Design: Sex, ...
5-azacytidine and 6-azauridine. Finally, he was active in the field of insect juvenile hormones. Šorm was the author or co- ...
... azauridine MeSH D13.570.685.852.250 - 3-deazauridine MeSH D13.570.685.852.300 - deoxyuridine MeSH D13.570.685.852.300.150 - ... azauridine MeSH D13.570.800.892.250 - 3-deazauridine MeSH D13.570.800.892.628 - pseudouridine MeSH D13.570.800.892.800 - ...
6-AZAURIDINE 6-azauridine Azauridine PubChem Notes: Azauridine A triazine nucleoside used as an antineoplastic antimetabolite. It interferes with ... Azauridine CHEBI:35668 2beta-D-Ribofuranosyl-as-triazine-3,5(2H,4H)-dione 2-beta-D-Ribofuranosyl-1,2,4-triazine-3,5(2H,4H)- ...
2-Thio-6-azauridine 99%; CAS Number: 27089-56-1; EC Number: 248-218-7; Synonym: 6-Aza-2-thiouridine; Linear Formula: C8H11N3O5S ...
Treatment of Polycythemia Vera with Azauridine and Azaribine RONALD C. DECONTI, M.D.; PAUL CALABRESI, M.D. ... DECONTI RC, CALABRESI P. Treatment of Polycythemia Vera with Azauridine and Azaribine. Ann Intern Med. ;73:575-579. doi: ... The pyrimidine analog 6-azauridine or its oral derivative, azaribine, was used to control polycythemia vera in five patients. ...
6-AZA URIDINE 5-MONOPHOSPHATE. C8 H12 N3 O9 P. LRVZOSYMNMNQFR-SHUUEZRQSA-N. Ligand Interaction. ... Crystal structure of the orotidine 5-monophosphate decarboxylase from Saccharomyces cerevisiae complexed with 6-azauridine 5- ...
Beneficial Effects of Triacetyl Azauridine in Psoriasis and Mycosis Fungoides PAUL CALABRESI, M.D.; RAYMOND W. TURNER, M.D. ... Beneficial Effects of Triacetyl Azauridine in Psoriasis and Mycosis Fungoides. Ann Intern Med. 1966;64:352-371. doi: 10.7326/ ...
6-Azauridine is listed in the Worlds largest and most authoritative dictionary database of abbreviations and acronyms ... Looking for online definition of 6-Azauridine or what 6-Azauridine stands for? ... 6-Azauridine - What does 6-Azauridine stand for? The Free Dictionary https://acronyms.thefreedictionary.com/6-Azauridine ...
Learn more about 6-azauridine. We enable science by offering product choice, services, process excellence and our people make ...
6-AZA URIDINE 5-MONOPHOSPHATE. Find entries where: UP6. is present as a standalone ligand in 23 entries ...
The antifertility effect of 2, 3, 5tri-O-acetyl-6-azauridine. I. ... The antifertility effect of 2, 3, 5tri-O-acetyl-6-azauridine. I. ...
Sensitive to interferon (9); resistant to 6-azauridine (9,11) Virion Morphology. ...
Inactivated by 1 M MgCl2 at 50C for 1 hour (4); trypsin, papain, 6-azauridine (14,16) ...
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6-Azauridine 2, 3,5-triacetate. Catalog #: B1025 , Datasheet Starting at: $125.00 ...
Azaribine (triacetyl-6-azauridine) is a drug which was developed for the treatment of psoriasis, and also has anti-cancer and ... It is a prodrug which is metabolised to the nucleoside analogue 6-azauridine in the body. Azaribine was approved for clinical ... Elis J, Rasková H (March 1972). "New indications for 6-azauridine treatment in man. A review". European Journal of Clinical ... triacetyl-6-azauridine". Cancer Research. 23: 444-53. PMID 14023746. Morrey JD, Smee DF, Sidwell RW, Tseng C (July 2002). " ...
6-Azauridine. 15.07. Antimetabolit / Antiviral. NA. NA. Irinotecan. 14.14. Topisomerase jeg hæmmer. +. 0,63. ...
... azauridine, thioguanine, vinblastine, vincristine, and bleomycin; anti-inflammatories, such as aurothioglucose and gold sodium ...
... azauridine, azaribine, fluorodeoxyuridine, deoxycoformycin, mercaptopurine, etc.; or a platinum coordination complex, such as ...
Crance, J.M.; Scaramozzino, N.; Jouan, A.; Garin, D. Interferon, ribavirin, 6-azauridine and glycyrrhizin: Antiviral compounds ...
6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine; androgens such as calusterone, ...
6-azauridine, glycyrrhizin, and interferon. There has also been interest in vaccine development, including virus-like particle ...
Interferon, ribavirin, 6-azauridine and glycyrrhizin: antiviral compounds active against pathogenic flaviviruses. Antiviral Res ...
The N-hetero ring is a triazine ring, including hydrogenated (e.g., 6-azauridine, etc.): This subclass is indented under ...
Interferon, ribavirin, 6-azauridine, and glycyrrhizin: antiviral compounds active against pathogenic flaviviruses.. Antiviral ... showed that ribavirin and 6-azauridine were active but not selective inhibitors when assessed with regard to inhibition of cell ... In a comparison of the antiviral potential of 6-azauridine, ribavirin, and glycyrrhizin against several pathogenic flaviviruses ... We assessed the antiviral potential of ribavirin, 6-azauridine, pyrazofurin, mycophenolic acid, and glycyrrhizin against two ...
Large amounts of orotidine are excreted in the urine of cancer patients treated with 6-azauridine. The symbol commonly used for ...
6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine, 5-FU; androgens such as ...
6185334 - Stimulation by 6-azauridine of carbamoyl phosphate synthesis for pyrimidine biosynthesi.... 25466144 - Comparison of ...
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Keywords: tim barrel, orotidine 5-monophosphate decarboxylase, 6-azauridine 5-monophosphate, LYASE. Deposited on 2010-10-21, ... monophosphate decarboxylase from Methanobacterium thermoautotrophicum complexed with 6-azauridine 5-monophosphate. Class: ...
Crance, J.M., Scaramozzino, N., Jouan, A., and Garin, D. (2003). Interferon, ribavirin, 6-azauridine and glycyrrhizin: ...
Interferon, ribavirin, 6-azauridine and glycyrrhizin: antiviral compounds active against pathogenic flaviviruses. Antiviral Res ...
  • Interferon, ribavirin, 6-azauridine and glycyrrhizin: antiviral compounds active against pathogenic flaviviruses. (ajtmh.org)
  • We assessed the antiviral potential of ribavirin, 6-azauridine, pyrazofurin, mycophenolic acid, and glycyrrhizin against two clinical isolates of coronavirus (FFM-1 and FFM-2) from patients with SARS admitted to the clinical centre of Frankfurt University, Germany. (thetreeofliberty.com)
  • In a comparison of the antiviral potential of 6-azauridine, ribavirin, and glycyrrhizin against several pathogenic flaviviruses, Crance and collegues 2 showed that ribavirin and 6-azauridine were active but not selective inhibitors when assessed with regard to inhibition of cell growth. (thetreeofliberty.com)
  • Investigators assessed the anti-viral activity of a variety of traditionally used pharmaceutical agents, including ribavirin, 6-azauridine, pyrazofurin, and mycophenolic acid, as well as glycyrrhizin. (jeffreybland.com)
  • The dose response curves for ribavirin, mycophenolic acid and 6 azauridine determined with the two EGFP and Rluc signals exposed sigmoidal, dose dependent reduction in each marker levels. (her2signaling.com)
  • Considering different kinds of nucleoside analogue has different characteristics, Creative Biolabs provides a pipeline of R&D services of antiviral nucleoside analogues based on multiple action mechanisms, including Remdesivir, NHC, BCX4430, Gemcitabine Hydrochloride, 6-Azauridine, Mizoribine, Acyclovir Fleximer, and Ribavirin for SARS-CoV-2 treatment research. (panajijournal.com)
  • The docking results demonstrated glycyrrhizin followed by azadirachtanin, mycophenolic acid, kushenol-w and 6-azauridine, as potential candidates. (bvsalud.org)
  • The 50% inhibitory concentrations had been around 1 mM for mycophenolic acid and 6 azauridine with each reporter genes, and 8. (her2signaling.com)
  • Large amounts of orotidine are excreted in the urine of cancer patients treated with 6-azauridine. (wikipedia.org)
  • The inhibitors of orotidine monophosphate decarboxylase, 6-azauridine and pyrazofurin, inhibited replication of SARS-CV at non-toxic doses with selectivity indices of 5 and 12, respectively. (thetreeofliberty.com)
  • The pyrimidine analog 6-azauridine or its oral derivative, azaribine, was used to control polycythemia vera in five patients. (annals.org)
  • Reduced supply of both purines, deoxyadenosine triphosphate (dATP) and deoxyguanosine triphosphate (dGTP), may be caused by hydroxyurea, 6-mercaptopurine (and probably by another purine antagonist azaserine), whilst reduced supply of both pyrimidine DNA precursors, dTTP and dCTP (deoxycytidine triphosphate) may be due to inherited orotic aciduria or to treatment with azauridine. (meta.org)
  • Azauridine A triazine nucleoside used as an antineoplastic antimetabolite. (scitoys.com)
  • It is a prodrug which is metabolised to the nucleoside analogue 6-azauridine in the body. (wikipedia.org)
  • Azaribine (triacetyl-6-azauridine) is a drug which was developed for the treatment of psoriasis, and also has anti-cancer and antiviral actions. (wikipedia.org)
  • Results on specimens obtained from patients taking methotrexate, carbamazepine, phenytoin, nitrous oxide, anti-convulsants, or 6-azauridine triacetates should be interpreted with caution as these substances interfere with homocysteine determination. (directlabs.com)
  • Furthermore, they have screened 727 compounds from the NIH collections of which two candidates including 6-azauridine and mitoxantrone inhibited replication of MP12. (hhs.gov)
  • Current status of clinical investigations with 6-Azauridine, 5-iodo-2'-deoxyuridine, and related derivatives. (rxdrugsinfo.com)
  • New indications for 6-azauridine treatment in man. (wikipedia.org)
  • Hyánek, J., Bremer, H. J. and Slavik, M. 'Homocystinuria' and urinary excretion of β-aminoacids in patients treated with 6-azauridine. (springer.com)
  • Combined effects of a mutant gene, paddlefoot, and a teratogen, 6-azauridine, on limb development of mouse embryos. (jax.org)