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1

Deng, Wei-Wei, Riko Katahira, and Hiroshi Ashihara. "Short Term Effect of Caffeine on Purine, Pyrimidine and Pyridine Metabolism in Rice (Oryza sativa) Seedlings." Natural Product Communications 10, no. 5 (2015): 1934578X1501000. http://dx.doi.org/10.1177/1934578x1501000510.

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As part of our studies on the physiological and ecological function of caffeine, we investigated the effect of exogenously supplied caffeine on purine, pyrimidine and pyridine metabolism in rice seedlings. We examined the effect of 1 mM caffeine on the in situ metabolism of 14C-labelled adenine, guanine, inosine, uridine, uracil, nicotinamide and nicotinic acid. The segments of 4-day-old dark-grown seedlings were incubated with these labelled compounds for 6 h. For purines, the incorporation of radioactivity from [8-14C]adenine and [8-14C]guanine into nucleotides was enhanced by caffeine; in c
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2

Pels Rijcken, W. R., B. Overdijk, D. H. van den Eijnden, and W. Ferwerda. "Pyrimidine nucleotide metabolism in rat hepatocytes: evidence for compartmentation of nucleotide pools." Biochemical Journal 293, no. 1 (1993): 207–13. http://dx.doi.org/10.1042/bj2930207.

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Pyrimidine nucleotide metabolism in rat hepatocytes was studied by measurement of the labelling kinetics of the various intermediates after double labelling with [14C]orotic acid and [3H]cytidine, the precursors for the de novo and the salvage pathways respectively. For the uridine nucleotides, differences were found for the 14C/3H ratios in the UDP-sugars, in UMP (of RNA) and in their precursor UTP, suggesting the existence of separated flows of the radioactive precursors through the de novo and the salvage pathways. Higher ratios in the UDP-sugars, which are synthesized in the cytoplasm, and
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3

Pels Rijcken, W. R., G. J. M. Hooghwinkel, and W. Ferwerda. "Pyrimidine metabolism and sugar nucleotide synthesis in rat liver." Biochemical Journal 266, no. 3 (1990): 777–83. http://dx.doi.org/10.1042/bj2660777.

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With radioactive precursors, the labelling kinetics of the soluble pyrimidine nucleotides and of RNA were measured in rat liver to determine the contribution of the metabolic flows through synthesis de novo and the salvage pathway. To separate and quantify all pyrimidine nucleotides, an h.p.l.c. technique was developed using anion-exchange chromatography and reversed-phase chromatography. The concentrations of cytidine nucleotides were in the range of 30-45 nmol/g wet weight, and the concentrations of the uridine phosphates and of the UDP-sugars were approx. 6 and 20 times higher respectively.
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4

Sprenger, Hans-Georg, Thomas MacVicar, Amir Bahat, et al. "Cellular pyrimidine imbalance triggers mitochondrial DNA–dependent innate immunity." Nature Metabolism 3, no. 5 (2021): 636–50. http://dx.doi.org/10.1038/s42255-021-00385-9.

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AbstractCytosolic mitochondrial DNA (mtDNA) elicits a type I interferon response, but signals triggering the release of mtDNA from mitochondria remain enigmatic. Here, we show that mtDNA-dependent immune signalling via the cyclic GMP–AMP synthase‒stimulator of interferon genes‒TANK-binding kinase 1 (cGAS–STING–TBK1) pathway is under metabolic control and is induced by cellular pyrimidine deficiency. The mitochondrial protease YME1L preserves pyrimidine pools by supporting de novo nucleotide synthesis and by proteolysis of the pyrimidine nucleotide carrier SLC25A33. Deficiency of YME1L causes i
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5

Rowe, Peter B., and Annette Kalaizis. "Serine metabolism in rat embryos undergoing organogenesis." Development 87, no. 1 (1985): 137–44. http://dx.doi.org/10.1242/dev.87.1.137.

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Rat embryos (9·5 days gestation) were cultured for 48 h in heat-inactivated homologous serum containing [3-14C] serine. Analysis of the distribution of the radioactive label in the conceptus demonstrated that almost one half of the incorporated serine was cleaved to provide one-carbon units for the synthesis of purine and pyrimidine nucleotides. Analysis of the free amino acids in the serum, the exocoelomic fluid and the cells of the yolk sac and the embryo showed that there was a variably selective increase in the concentration of amino acids in the exocoelomic fluid compared with the serum a
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6

Chiarelli, Laurent, Andrea Mattevi, Alessandro Galizzi, et al. "Functional Analysis of Two Mutants of Pyrimidine 5′ Nucleotidase Causing Nonspherocytic Hemolytic Anemia." Blood 104, no. 11 (2004): 1592. http://dx.doi.org/10.1182/blood.v104.11.1592.1592.

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Abstract Pyrimidine 5′-nucleotidase type-I (P5′N-1) catalyzes the dephosphorylation of UMP and CMP to their respective nucleosides. In red blood cells, the enzyme has a major role in the catabolism of nucleotides formed from RNA degradation. P5′N-1 possesses also phospho-transferase activity suggesting an additional role of the enzyme in nucleotide metabolism. P5′N-1 deficiency is an autosomal recessive disorder characterized by hemolytic nonspherocytic anemia, heavy basophilic stippling in the peripheral blood smear, and accumulation of pyrimidine nucleotides within the erythrocytes. P5′N-1 d
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7

Yao, Yixin, Yang Liu, Hui Guo, et al. "Metabolic Profiling Identifies De Novo Nucleotide Synthesis As a Potential Metabolic Vulnerability for Targeted Therapy Against Mantle Cell Lymphoma." Blood 132, Supplement 1 (2018): 2945. http://dx.doi.org/10.1182/blood-2018-99-112192.

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Abstract Introduction: Cancer cells exhibit dramatic alterations in cellular metabolism, such as enhanced de novo nucleotide synthesis, to support cell growth, proliferation and survival. The abundance of the nucleotide pool as well as the level and activity of different rate-limiting enzymes belonging to the nucleotide synthetic pathway limit the maximal proliferative capacity of cells. Maintenance of an adequate pool of deoxyribonucleotide triphosphates is essential for DNA replication and DNA repair, and consequently, the genetic integrity of nuclear and mitochondrial genomes. We and others
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8

Kartha, S., and F. G. Toback. "Purine nucleotides stimulate DNA synthesis in kidney epithelial cells in culture." American Journal of Physiology-Renal Physiology 249, no. 6 (1985): F967—F972. http://dx.doi.org/10.1152/ajprenal.1985.249.6.f967.

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Adenine nucleotides infused into animals with acute renal failure appear to enhance recovery of kidney function and structure. To determine whether these compounds could act by a direct effect on renal cell metabolism, their capacity to stimulate DNA synthesis was evaluated in cultures of monkey kidney epithelial cells (BSC-1 line). AMP and ADP enhanced DNA synthesis by threefold more than was previously observed with other mitogens for these cells. Guanosine and inosine and their nucleotides and adenosine and ATP were also mitogenic but to a lesser extent, whereas pyrimidine derivatives were
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9

Fermo, Elisa, Anna Marcello, Paola Bianchi, et al. "Pyrimidine 5′ Nucleotidase Deficiency: Clinical and Molecular Characterization of Two New Italian Patients." Blood 106, no. 11 (2005): 3711. http://dx.doi.org/10.1182/blood.v106.11.3711.3711.

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Abstract Hereditary pyrimidine 5′ nucleotidase deficiency (P5′N) is the most frequent abnormality of the red cell nucleotide metabolism causing hereditary non-spherocytic hemolytic anemia. The disorder is characterized by mild-to-moderate hemolytic anemia associated with reticulocytosis and hyperbilirubinemia and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. P5′N-1 gene is localized on 7p15-p14; eighteen mutations have been so far identified in 27 unrelated families, 6 of them of Italian origin. The aim of this study is to describe the hematological,
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10

Arbade, Gajanan Kashinathrao, and Sandeep Kumar Srivastava. "Cloning, expression, purification, crystallization and preliminary X-ray diffraction studies of NAD synthetase from methicillin-resistantStaphylococcus aureus." Acta Crystallographica Section F Structural Biology Communications 71, no. 6 (2015): 763–69. http://dx.doi.org/10.1107/s2053230x15007906.

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Staphylococcus aureusis an important human and animal pathogen that causes a wide range of infections. The prevalence of multidrug-resistantS. aureusstrains in both hospital and community settings makes it imperative to characterize new drug targets to combatS. aureusinfections. In this context, enzymes involved in NAD metabolism and synthesis are significant drug targets as NAD is a central player in several cellular processes. NAD synthetase catalyzes the last step in the biosynthesis of nicotinamide adenine dinucleotide, making it a crucial intermediate enzyme linked to the biosynthesis of
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11

Gu, Xiaorong, Rita Tohme, Mendel Goldfinger, et al. "Venetoclax Inhibition of Pyrimidine Synthesis Guides Methods for Integration with Decitabine or 5-Azacytidine That Are Non-Myelosuppressive." Blood 136, Supplement 1 (2020): 26–27. http://dx.doi.org/10.1182/blood-2020-143200.

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Venetoclax (Ven) administered daily with pulse-cycled parenteral decitabine (Dec) or 5-azacytidine (5Aza) is standard therapy for acute myeloid leukemia (AML) in the elderly. In practice, toxicity/myelosuppression is frequent, and prompts Ven dose reductions, but by guess-work, because the mechanism downstream of BCL2-inhibition by which Ven augments Dec/5Aza activity is unclear. For the first time, we show that Ven inhibits de novo pyrimidine synthesis, an effect that can guide its integration with Dec/5Aza in a way that enhances anti-AML activity without suppressing normal myelopoiesis. Dec
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12

Guseinova, Sadagat Ganbarovna, S. S. Imamverdieva, E. E. Mustafaeva, M. Yu Mamedova, and K. N. Yusifova. "EFFICIENCY OF APPLICATION OF INTERFERENCY THERAPY IN COMPLEX WITH PYRIMIDINE NUCLEOTIDES IN PATIENTS WITH VERTEBROGENIC RADICULOPATHIES." Russian Journal of Physiotherapy, Balneology and Rehabilitation 16, no. 6 (2017): 325–30. http://dx.doi.org/10.18821/1681-3456-2017-16-5-325-330.

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Clinical-neurophysiological bases of the combined use of Nucleo CMF forte preparation and interference therapy in the complex treatment of patients with vertebrogenic radiculopathies were studied. The beneficial effect of this therapeutic complex on the clinical course of the disease, more pronounced analgesic effect and regression of clinical manifestations, as well as improvement of quality of life indicators were proved. It has been established that the therapeutic effect of the complex application of Nucleo CMF forte and interference therapy lies in the improvement in the afferent and effe
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13

Gibb, C. A., D. I. Cook, L. Delbridge, and A. D. Conigrave. "Pharmacological characterization of the nucleotide receptors that mobilize Ca2+ ions in human parathyroid cells." Journal of Endocrinology 142, no. 2 (1994): 277–83. http://dx.doi.org/10.1677/joe.0.1420277.

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Abstract We have used the fluorescent probe fura-2 to perform agonist studies of the receptor(s) that mobilizes Ca2+ ions in response to extracellular ATP in human parathyroid cells. Extracellular ATP induced Ca2+ responses in both normal and adenomatous parathyroid cells. Activation resulted in an initial small transient response during which Ca2+ ions were released from intracellular stores, followed by a prominent plateau response during which Ca2+ ions entered the cells from the extracellular fluid. The responses exhibited moderate desensitization upon repeated stimulation with ATP, and th
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14

Chikenji, Tohru, Kazuko Kita, and Masamiti Tatibana. "Stimulation of de novo biosynthesis of purine and pyrimidine nucleotides in the liver of rats following burn injury." Metabolism 37, no. 12 (1988): 1114–19. http://dx.doi.org/10.1016/0026-0495(88)90186-2.

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15

Dong, Qing, Ying-Xin Zhang, Quan Zhou, et al. "UMP Kinase Regulates Chloroplast Development and Cold Response in Rice." International Journal of Molecular Sciences 20, no. 9 (2019): 2107. http://dx.doi.org/10.3390/ijms20092107.

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Pyrimidine nucleotides are important metabolites that are building blocks of nucleic acids, which participate in various aspects of plant development. Only a few genes involved in pyrimidine metabolism have been identified in rice and the majority of their functions remain unclear. In this study, we used a map-based cloning strategy to isolate a UMPK gene in rice, encoding the UMP kinase that phosphorylates UMP to form UDP, from a recessive mutant with pale-green leaves. In the mutant, UDP content always decreased, while UTP content fluctuated with the development of leaves. Mutation of UMPK r
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16

WORMIT, Alexandra, Michaela TRAUB, Martin FLÖRCHINGER, H. Ekkehard NEUHAUS, and Torsten MÖHLMANN. "Characterization of three novel members of the Arabidopsis thaliana equilibrative nucleoside transporter (ENT) family." Biochemical Journal 383, no. 1 (2004): 19–26. http://dx.doi.org/10.1042/bj20040389.

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Research on metabolism of nucleotides and their derivatives has gained increasing interest in the recent past. This includes de novo synthesis, analysis of salvage pathways, breakdown and transport of nucleotides, nucleosides and nucleobases. To perform a further step towards the analysis of nucleoside transport in Arabidopsis, we incubated leaf discs with various radioactively labelled nucleosides. Leaf cells imported labelled nucleosides and incorporated these compounds into RNA, but not into DNA. Furthermore, we report on the biochemical properties of three so far uncharacterized members of
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17

Von Ohlen, Tonia, Alison Luce-Fedrow, M. Teresa Ortega, Roman R. Ganta, and Stephen K. Chapes. "Identification of Critical Host Mitochondrion-Associated Genes during Ehrlichia chaffeensis Infections." Infection and Immunity 80, no. 10 (2012): 3576–86. http://dx.doi.org/10.1128/iai.00670-12.

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ABSTRACTEhrlichia chaffeensisis an obligate intracellular bacterium that causes human monocytic ehrlichiosis (HME). To determine what host components are important for bacterial replication, we performed microarray analysis onDrosophila melanogasterS2 cells by comparing host gene transcript levels between permissive and nonpermissive conditions forE. chaffeensisgrowth. Five-hundred twenty-seven genes had increased transcript levels unique to permissive growth conditions 24 h postinfection. We screened adult flies that were mutants for several of the “permissive” genes for the ability to suppor
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18

Hanczakowska, Ewa, and Barbara Niwińska. "Glutamine as a Feed Supplement for Piglets: a Review / Glutamina jako dodatek do paszy dla prosiąt: przegląd." Annals of Animal Science 13, no. 1 (2013): 5–152. http://dx.doi.org/10.2478/v10220-012-0054-y.

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Abstract Weaning is a crucial moment in a piglet’s life. It is characterized by a generally low nutrient intake and adverse changes in the small intestinal mucosa. Proper feeding is therefore necessary to ensure normal development of the gastrointestinal tract. One substance that could provide intestinal epithelial cells with necessary energy is the amino acid glutamine. It improves epithelium structure and accelerates the growth of intestinal villi in which nutrients are absorbed, thus improving feed utilization and growth performance in piglets. The effect of glutamine on intestinal microflo
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19

Szczuko, Małgorzata, Maciej Ziętek, Danuta Kulpa, and Teresa Seidler. "Riboflavin - properties, occurrence and its use in medicine." Pteridines 30, no. 1 (2019): 33–47. http://dx.doi.org/10.1515/pteridines-2019-0004.

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Abstract Riboflavin is built on an isoalloxazin ring, which contains three sixcarbon rings: benzoic, pyrazine and pyrimidine. Riboflavin is synthesized by some bacteria, but among humans and animals, the only source of flavin coenzymes (FAD, FMN) is exogenous riboflavin. Riboflavin transport in enterocytes takes place via three translocators encoded by the SLC52 gene. Deficiency of dietary riboflavin has wide ranging implications for the efficacy of other vitamins, the mechanism of cellular respiration, lactic acid metabolism, hemoglobin, nucleotides and amino acid synthesis. In studies it was
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20

Dörries, Kirsten, Rabea Schlueter, and Michael Lalk. "Impact of Antibiotics with Various Target Sites on the Metabolome of Staphylococcus aureus." Antimicrobial Agents and Chemotherapy 58, no. 12 (2014): 7151–63. http://dx.doi.org/10.1128/aac.03104-14.

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ABSTRACTIn this study, global intra- and extracellular metabolic profiles were exploited to investigate the impact of antibiotic compounds with different cellular targets on the metabolome ofStaphylococcus aureusHG001. Primary metabolism was largely covered, yet uncommon staphylococcal metabolites were detected in the cytosol ofS. aureus, including sedoheptulose-1,7-bisphosphate and the UDP-MurNAc-pentapeptide with an alanine-seryl residue. By comparing the metabolic profiles of unstressed and stressed staphylococcal cells in a time-dependent manner, we found far-ranging effects within the met
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21

Presant, C. A., W. Wolf, M. J. Albright, et al. "Human tumor fluorouracil trapping: clinical correlations of in vivo 19F nuclear magnetic resonance spectroscopy pharmacokinetics." Journal of Clinical Oncology 8, no. 11 (1990): 1868–73. http://dx.doi.org/10.1200/jco.1990.8.11.1868.

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We previously reported that fluorouracil (5FU) accumulation and metabolism in human livers and tumors can be studied by in vivo nuclear magnetic resonance spectroscopy (NMRS). We have extended these observations by evaluating the pharmacokinetics of 5FU in the tumors of 11 patients with carcinoma of the breast, colon, endometrium, cervix, and kidney, using 19F-NMRS in a 1.5 Magnetom (Siemens Medical Systems, Cerrito, CA) magnetic resonance imaging unit (MRI). These NMRS measurements detected a long-lived tumor pool of 5FU in six of 11 tumors in our patients including carcinomas in the pelvis,
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22

Clark, M. G., S. M. Richards, M. Hettiarachchi, et al. "Release of purine and pyrimidine nucleosides and their catabolites from the perfused rat hindlimb in response to noradrenaline, vasopressin, angiotensin II and sciatic-nerve stimulation." Biochemical Journal 266, no. 3 (1990): 765–70. http://dx.doi.org/10.1042/bj2660765.

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Uric acid and uracil were released at constant rates (0.95 and 0.4 nmol/min per g respectively) by the perfused rat hindlimb. Noradrenaline, vasopressin or angiotensin II further increased the release of these substances 2-5-fold, coinciding with increases in both perfusion pressure (vasoconstriction) and O2 uptake. The hindlimb also released, but in lesser amounts, uridine, hypoxanthine, xanthine, inosine and guanosine, and all but hypoxanthine and guanosine were increased during intense vasoconstriction. Uric acid and uracil releases were increased by noradrenaline in a dose-dependent manner
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23

Piya, Sujan, Marla Weetall, Josephine Sheedy, et al. "The Novel Dihydroorotate Dehydrogenase (DHODH) Inhibitor PTC299 Inhibit De Novo Pyrimidine Synthesis with Broad Anti-Leukemic Activity Against Acute Myeloid Leukemia." Blood 136, Supplement 1 (2020): 8–9. http://dx.doi.org/10.1182/blood-2020-139940.

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Introduction: Acute myeloid leukemia (AML) is characterized by both aberrant proliferation and differentiation arrest at hematopoietic progenitor stages 1,2. AML relies upon de novo nucleotide synthesis to meet a dynamic metabolic landscape and to provide a sufficient supply of nucleotides and other macromolecules 3,4. Hence, we hypothesized that inhibition of de novo nucleotide synthesis would lead to depletion of the nucleotide pool and pyrimidine starvation in leukemic cells compared to their non-malignant counterparts and impact proliferative and differentiation inhibition pathways. PTC299
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24

Kleineidam, Anna, Stefano Vavassori, Ke Wang, Lilian M. Schweizer, Peter Griac, and Michael Schweizer. "Valproic acid- and lithium-sensitivity in prs mutants of Saccharomyces cerevisiae." Biochemical Society Transactions 37, no. 5 (2009): 1115–20. http://dx.doi.org/10.1042/bst0371115.

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Prs [PRPP (phosphoribosyl pyrophosphate) synthetase] catalyses the transfer of pyrophosphate from ATP to ribose 5-phosphate, thereby activating the pentose sugar for incorporation into purine and pyrimidine nucleotides. The Saccharomyces cerevisiae genome contains five genes, PRS1–PRS5, whose products display characteristic PRPP and bivalent-cation-binding sites of Prs polypeptides. Deletion of one or more of the five PRS genes has far-reaching and unexpected consequences, e.g. impaired cell integrity, temperature-sensitivity and sensitivity to VPA (valproic acid) and LiCl. CTP pools in prs1Δ
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25

Xin, Yanli, Yanliang Wang, Liang Zhong, Bingbo Shi, Hui Liang, and Jianyong Han. "Slc25a36 modulates pluripotency of mouse embryonic stem cells by regulating mitochondrial function and glutathione level." Biochemical Journal 476, no. 11 (2019): 1585–604. http://dx.doi.org/10.1042/bcj20190057.

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Abstract Mitochondria play a central role in the maintenance of the naive state of embryonic stem cells. Many details of the mechanism remain to be fully elucidated. Solute carrier family 25 member 36 (Slc25a36) might regulate mitochondrial function through transporting pyrimidine nucleotides for mtDNA/RNA synthesis. Its physical role in this process remains unknown; however, Slc25a36 was recently found to be highly expressed in naive mouse embryonic stem cells (mESCs). Here, the function of Slc25a36 was characterized as a maintenance factor of mESCs pluripotency. Slc25a36 deficiency (via knoc
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26

Dragon, Stefanie, Rainer Hille, Robert Götz, and Rosemarie Baumann. "Adenosine 3′:5′-Cyclic Monophosphate (cAMP)-Inducible Pyrimidine 5′-Nucleotidase and Pyrimidine Nucleotide Metabolism of Chick Embryonic Erythrocytes." Blood 91, no. 8 (1998): 3052–58. http://dx.doi.org/10.1182/blood.v91.8.3052.3052_3052_3058.

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Terminally differentiating erythrocytes degrade most of their RNA with subsequent release of mononucleotides. Pyrimidine mononucleotides are preferentially cleaved by an erythrocyte-specific pyrimidine 5′-nucleotidase; deficiency of this enzyme causes hemolytic anemia in humans. Details of the regulation of its activity during erythroid differentiation are unknown. The present study arose from the observation that the immature red blood cells (RBCs) of mid-term chick embryos contain high concentrations of uridine 5′-triphosphate (UTP) (5 to 6 mmol/L), which decline rapidly from days 13 to 14 o
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27

Chiarelli, Laurent R., Paola Bianchi, Elisa Fermo, et al. "Functional analysis of pyrimidine 5′-nucleotidase mutants causing nonspherocytic hemolytic anemia." Blood 105, no. 8 (2005): 3340–45. http://dx.doi.org/10.1182/blood-2004-10-3895.

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Abstract Inherited pyrimidine 5′-nucleotidase type I (P5′N-1) deficiency is the third most common erythrocyte enzymopathy that causes hemolysis. Fourteen different mutations have been identified to date. We have investigated the molecular bases of the disease by studying the biochemical properties of the recombinant wild-type human enzyme and 4 variant proteins (D87V, L131P, N179S, and G230R) bearing missense mutations found in patients affected by nonspherocytic hemolytic anemia. P5′N-1 is a relatively stable protein and has essentially identical catalytic efficiency toward cytidine monophosp
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28

Amici, Adolfo, Ersilia Ferretti, and Giulio Magni. "Nucleotide metabolism in human erythrocytes: Purification and properties of specific pyrimidine 5'-nucleotidase." Collection of Czechoslovak Chemical Communications 55, s1 (1990): 153–56. http://dx.doi.org/10.1135/cccc1990s153.

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29

Aldritt, S. M., P. Tien, and C. C. Wang. "Pyrimidine salvage in Giardia lamblia." Journal of Experimental Medicine 161, no. 3 (1985): 437–45. http://dx.doi.org/10.1084/jem.161.3.437.

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We have found that the anaerobic protozoan parasite Giardia lamblia is incapable of de novo pyrimidine metabolism, as shown by its inability to incorporate orotate, bicarbonate, and aspartate into the pyrimidine nucleotide pool. Results from high performance liquid chromatography of pyrimidine and pyrimidine nucleoside pulse-labeled nucleotide pools and enzyme assays suggest that the parasite satisfies its pyrimidine nucleotide needs predominantly through salvage of uracil by a cytoplasmic uracil phosphoribosyltransferase. Exogenous uridine and cytidine are primarily converted to uracil by the
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30

Moffatt, Barbara A., and Hiroshi Ashihara. "Purine and Pyrimidine Nucleotide Synthesis and Metabolism." Arabidopsis Book 1 (January 2002): e0018. http://dx.doi.org/10.1199/tab.0018.

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31

Bizarro, Cristiano Valim, and Desirée Cigaran Schuck. "Purine and pyrimidine nucleotide metabolism in Mollicutes." Genetics and Molecular Biology 30, no. 1 suppl (2007): 190–201. http://dx.doi.org/10.1590/s1415-47572007000200005.

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32

Stasolla, Claudio, Riko Katahira, Trevor A. Thorpe, and Hiroshi Ashihara. "Purine and pyrimidine nucleotide metabolism in higher plants." Journal of Plant Physiology 160, no. 11 (2003): 1271–95. http://dx.doi.org/10.1078/0176-1617-01169.

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33

Calvo-Vidal, Nieves, Jayeshkumar Patel, Jan Krumsiek, et al. "Hsp90 at the Hub of Metabolic Homeostasis in Malignant B Cells." Blood 124, no. 21 (2014): 1764. http://dx.doi.org/10.1182/blood.v124.21.1764.1764.

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Abstract Reprogramming of tumor cell metabolism contributes to disease aggressiveness and chemoresistance, but how this process is regulated on the molecular levels is unclear. Hsp90 regulates diverse cellular processes through its interaction with co-chaperones and client proteins. Although basally expressed, Hsp90 is almost universally overexpressed in malignant cells due to increased levels of internal (oxidants, genomic instability, unfolded proteins) and external (hypoxia, nutrients limitation, drugs) stressors. Indeed, Hsp90 is starting to be acknowledged also for its role as an integrat
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34

Yang, Kailin, Xiuxing Wang, Qiulian Wu, et al. "STEM-22. TARGETING PYRIMIDINE SYNTHESIS ACCENTUATES MOLECULAR THERAPY RESPONSE IN GLIOBLASTOMA STEM CELLS." Neuro-Oncology 21, Supplement_6 (2019): vi238. http://dx.doi.org/10.1093/neuonc/noz175.995.

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Abstract Glioblastoma stem cells (GSCs) reprogram glucose metabolism by hijacking high-affinity glucose uptake to survive in a nutritionally dynamic microenvironment. Here, we trace metabolic aberrations in GSCs to link core genetic mutations in glioblastoma to dependency on de novo pyrimidine synthesis. Targeting the pyrimidine synthetic rate-limiting step enzyme carbamoyl-phosphate synthetase 2, aspartate transcarbamyolase, dihydroorotase (CAD) or the critical downstream enzyme, dihydroorotate dehydrogenase (DHODH) inhibited GSC survival, self-renewal, and in vivo tumor initiation through th
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35

FAIRBANKS, Lynette D., Gabriella JACOMELLI, Vanna MICHELI, Tina SLADE, and H. Anne SIMMONDS. "Severe pyridine nucleotide depletion in fibroblasts from Lesch–Nyhan patients." Biochemical Journal 366, no. 1 (2002): 265–72. http://dx.doi.org/10.1042/bj20020148.

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The relationship between a complete deficiency of the purine enzyme hypoxanthine-guanine phosphoribosyltransferase and the neurobehavioural abnormalities in Lesch—Nyhan disease remains an enigma. In vitro studies using lymphoblasts or fibroblasts have evaluated purine and pyrimidine metabolism with conflicting results. This study focused on pyridine nucleotide metabolism in control and Lesch—Nyhan fibroblasts using radiolabelled salvage precursors to couple the extent of uptake with endocellular nucleotide concentrations. The novel finding, highlighted by specific culture conditions, was a mar
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36

Wang, Xiuxing, Kailin Yang, Qiulian Wu, et al. "Targeting pyrimidine synthesis accentuates molecular therapy response in glioblastoma stem cells." Science Translational Medicine 11, no. 504 (2019): eaau4972. http://dx.doi.org/10.1126/scitranslmed.aau4972.

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Glioblastoma stem cells (GSCs) reprogram glucose metabolism by hijacking high-affinity glucose uptake to survive in a nutritionally dynamic microenvironment. Here, we trace metabolic aberrations in GSCs to link core genetic mutations in glioblastoma to dependency on de novo pyrimidine synthesis. Targeting the pyrimidine synthetic rate-limiting step enzyme carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD) or the critical downstream enzyme dihydroorotate dehydrogenase (DHODH) inhibited GSC survival, self-renewal, and in vivo tumor initiation through the depletion
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37

Yang, Kailin, Xiuxing Wang, Qiulian Wu, et al. "FSMP-08. TARGETING PYRIMIDINE SYNTHESIS ACCENTUATES MOLECULAR THERAPY RESPONSE IN GLIOBLASTOMA STEM CELLS." Neuro-Oncology Advances 3, Supplement_1 (2021): i17. http://dx.doi.org/10.1093/noajnl/vdab024.072.

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Abstract Glioblastoma stem cells (GSCs) reprogram glucose metabolism by hijacking high-affinity glucose uptake to survive in a nutritionally dynamic microenvironment. Here, we trace metabolic aberrations in GSCs to link core genetic mutations in glioblastoma to dependency on de novo pyrimidine synthesis. Targeting the pyrimidine synthetic rate-limiting step enzyme carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD) or the critical downstream enzyme dihydroorotate dehydrogenase (DHODH) inhibited GSC survival, self-renewal, and in vivo tumor initiation through the
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38

Wales, Melinda E., Mary G. Mann-Dean, and James R. Wild. "Characterization of pyrimidine metabolism in the cellular slime mold, Dictyostelium discoideum." Canadian Journal of Microbiology 35, no. 4 (1989): 432–38. http://dx.doi.org/10.1139/m89-066.

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The arginine-independent, de novo biosynthetic pathway of pyrrolidines in Dictyostelium discoideum is initiated by a class II carbamoyl-phosphate synthetase (EC 6.3.5.5) specific for pyrimidine biosynthesis which utilized L-glutamine as its N donor and was partially inhibited by both UTP and CTP. The second step in the de novo pathway was provided by an unregulated aspartate transcarbamoylase (EC 2.1.3.2) which primarily appeared as a multimeric enzyme of 105 kilodaltons. The next enzyme, dihydroorotase (EC 3.5.2.3), was approximately 90–100 kilodaltons. Although the early enzymatic activities
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Martinussen, J., P. S. Andersen, and K. Hammer. "Nucleotide metabolism in Lactococcus lactis: salvage pathways of exogenous pyrimidines." Journal of Bacteriology 176, no. 5 (1994): 1514–16. http://dx.doi.org/10.1128/jb.176.5.1514-1516.1994.

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James, Sally G., Geoffrey J. Appleby, Kelly A. Miller, John T. Steen, Eric Q. Colquhoun, and Michael G. Clark. "Purine and pyrimidine nucleotide metabolism of vascular smooth muscle cells in culture." General Pharmacology: The Vascular System 27, no. 5 (1996): 837–44. http://dx.doi.org/10.1016/0306-3623(95)02087-x.

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41

Wu, Qijing, Qiong Huang, Mengting Sun, et al. "Unraveling metabolism heterogeneity in colorectal cancer and its implications in pan-cancer cohort." Journal of Clinical Oncology 38, no. 15_suppl (2020): e16016-e16016. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e16016.

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e16016 Background: Colorectal cancer (CRC) molecular subtype has been emphasized and links to biological and clinical behavior. However, comprehensive metabolism of CRC has not been characterized. Subtype-specific metabolic differences and immunometabolism phenotypes remain unclear. Therefore, this study performed metabolism clustering and explore its relation with immune phenotypes as well as prognosis predictive value. Methods: Transcriptome of TCGA CRC cohort was utilized to generate 113 KEGG metabolism pathway scores via GSVA algorithm. Consensus clustering were used to identify metabolism
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Lachant, Neil A., and Kouichi R. Tanaka. "Red cell metabolism in hereditary pyrimidine 5'-nucleotidase deficiency: effect of magnesium." British Journal of Haematology 63, no. 4 (1986): 615–23. http://dx.doi.org/10.1111/j.1365-2141.1986.tb07545.x.

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Hatse, Sigrid, Erik De Clercq, and Jan Balzarini. "Role of antimetabolites of purine and pyrimidine nucleotide metabolism in tumor cell differentiation." Biochemical Pharmacology 58, no. 4 (1999): 539–55. http://dx.doi.org/10.1016/s0006-2952(99)00035-0.

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44

Simmonds, H. A., S. Reiter, P. M. Davies, and J. S. Cameron. "Orotidine Accumulation in Human Erythrocytes during Allopurinol Therapy: Association with High Urinary Oxypurinol-7-Riboside Concentrations in Renal Failure and in the Lesch-Nyhan Syndrome." Clinical Science 80, no. 3 (1991): 191–97. http://dx.doi.org/10.1042/cs0800191.

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1. A compound identified as orotidine has been found in the erythrocytes of all subjects on allopurinol. 2. The erythrocyte orotidine concentrations were much higher in patients with renal failure or with the Lesch-Nyhan syndrome. 3. In addition, increased amounts of oxypurinol-7-riboside were excreted in the urine by both of these groups compared with control subjects or with patients with normal renal function on allopurinol. 4. A good correlation was found between urinary oxypurinol-7-riboside excretion and erythrocyte orotidine concentrations. 5. Increased erythrocyte levels of the pyrimid
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Kunjara, Sirilaksana, Milena Sochor, Murad Ali, Adrian Drake, A. Leslie Greenbaum, and Patricia McLean. "Pyrimidine nucleotide synthesis in the rat kidney in early diabetes." Biochemical Medicine and Metabolic Biology 46, no. 2 (1991): 215–25. http://dx.doi.org/10.1016/0885-4505(91)90069-w.

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Shi, Diana D., Adam C. Wang, Michael M. Levitt, et al. "DDRE-29. DE NOVO PYRIMIDINE SYNTHESIS IS A TARGETABLE VULNERABILITY IN IDH-MUTANT GLIOMA." Neuro-Oncology Advances 3, Supplement_1 (2021): i12—i13. http://dx.doi.org/10.1093/noajnl/vdab024.051.

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Abstract 70–90% of lower-grade gliomas and secondary glioblastomas harbor gain-of-function mutations in isocitrate dehydrogenase 1 (IDH1), causing overproduction of the oncometabolite (R)-2-hydroxyglutarate [(R)-2HG]. Although inhibitors of mutant IDH enzymes are effective in other cancers, including leukemia, they have shown guarded efficacy in preclinical and clinical brain tumor studies, thus underscoring the need to identify additional therapeutic targets in IDH mutant glioma. We sought to identify tumor-specific metabolic vulnerabilities induced by IDH1 mutations that could be exploited t
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Kato, Ryo, Tomoji Maeda, Toshihiro Akaike, and Ikumi Tamai. "Characterization of novel Na+-dependent nucleobase transport systems at the blood-testis barrier." American Journal of Physiology-Endocrinology and Metabolism 290, no. 5 (2006): E968—E975. http://dx.doi.org/10.1152/ajpendo.00160.2005.

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In the testis, nucleosides and nucleobases are important substrates of the salvage pathway for nucleotide biosynthesis, and one of the roles of Sertoli cells is to provide nutrients and metabolic precursors to spermatogenic cells located within the blood-testis barrier (BTB). We have already shown that concentrative and equilibrative nucleoside transporters are expressed and are functional in primary-cultured rat Sertoli cells as a BTB model, but little is known about nucleobase transport at the BTB or about the genes encoding specific nucleobase transporters in mammalian cells. In the present
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Lee, Heeju, Bora Lee, Yeonhee Kim, Sohyun Min, Eunjoo Yang, and Seungmin Lee. "Effects of Sodium Selenite Injection on Serum Metabolic Profiles in Women Diagnosed with Breast Cancer-Related Lymphedema—Secondary Analysis of a Randomized Placebo-Controlled Trial Using Global Metabolomics." Nutrients 13, no. 9 (2021): 3253. http://dx.doi.org/10.3390/nu13093253.

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In our previous study, intravenous (IV) injection of selenium alleviated breast cancer-related lymphedema (BCRL). This secondary analysis aimed to explore the metabolic effects of selenium on patients with BCRL. Serum samples of the selenium-treated (SE, n = 15) or the placebo-controlled (CTRL, n = 14) groups were analyzed by ultra-high-performance liquid chromatography with Q-Exactive Orbitrap tandem mass spectrometry (UHPLC-Q-Exactive Orbitrap/MS). The SE group showed a lower ratio of extracellular water to segmental water (ECW/SW) in the affected arm to ECW/SW in the unaffected arm (arm ECW
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Cihlar, Tomas, Ivan Votruba, Květoslava Horská, Radek Liboska, Ivan Rosenberg, and Antonín Holý. "Metabolism of 1-(S)-(3-Hydroxy-2-phosphonomethoxypropyl)cytosine (HPMPC) in Human Embryonic Lung Cells." Collection of Czechoslovak Chemical Communications 57, no. 3 (1992): 661–72. http://dx.doi.org/10.1135/cccc19920661.

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The acyclic nucleotide analogue HPMPC is in human embryonic lung cells, cultured in vitro, transformed to its mono- and diphosphates (HPMPCp and HPMPCpp) and HPMPCp-choline; the synthesis of HPMPCp is catalysed by pyrimidine nucleoside monophosphate kinase (EC 2.7.4.14); HPMPCp-choline (analogue of CDP-choline) is formed from HPMPCpp and choline phosphate in the presence of CTP:phosphorylcholine cytidylyltransferase (EC 2.7.7.15). These metabolites persist for a long time in the cellular pool even after HPMPC has been removed from the medium; on the other hand, they efflux to the medium. Neith
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Simmonds, H. A., L. D. Fairbanks, G. S. Morris, D. R. Webster, and E. H. Harley. "Altered erythrocyte nucleotide patterns are characteristic of inherited disorders of purine or pyrimidine metabolism." Clinica Chimica Acta 171, no. 2-3 (1988): 197–210. http://dx.doi.org/10.1016/0009-8981(88)90145-3.

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