Pyrimidine Metabolism: Dynamic and Versatile Pathways in Pathogens and Cellular Development

Department of Biological Sciences, Los Andes University, Bogota, Colombia

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Corresponding author: E-mail address: bhzimmermann@bhzonline.net (Barbara H. Zimmermann)

These authors contributed equally to this work.

摘要

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Abstract: The importance of pyrimidines lies in the fact that they are structural components of a broad spectrum of key molecules that participate in diverse cellular functions, such as synthesis of DNA, RNA, lipids, and carbohydrates. Pyrimidine metabolism encompasses all enzymes involved in the synthesis, degradation, salvage, interconversion and transport of these molecules. In this review, we summarize recent publications that document how pyrimidine metabolism changes under a variety of conditions, including, when possible, those studies based on techniques of genomics, transcriptomics, proteomics, and metabolomics. First, we briefly look at the dynamics of pyrimidine metabolism during nonpathogenic cellular events. We then focus on changes that pathogen infections cause in the pyrimidine metabolism of their host. Next, we discuss the effects of antimetabolites and inhibitors, and finally we consider the consequences of genetic manipulations, such as knock-downs, knock-outs, and knock-ins, of pyrimidine enzymes on pyrimidine metabolism in the cell.
- Pyrimidine metabolism /
- Pathogens /
- CAD /
- Dihydroorotase /
- Dihydroorotate dehydrogenase /
- UMP synthase
These authors contributed equally to this work.
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[1]	Ali, J.A.M., Creek, D.J., Burgess, K. et al. Mol. Pharmacol., 83 (2013),pp. 439-453
[2]	Andersen, G., Björnberg, O., Polakova, S. et al. A second pathway to degrade pyrimidine nucleic acid precursors in eukaryotes J. Mol. Biol., 380 (2008),pp. 656-666
[3]	Andersson Rasmussen, A., Kandasamy, D., Beck, H. et al. Eukaryot. Cell, 13 (2014),pp. 31-42
[4]	Angeletti, P.C., Engler, J.A. Adenovirus preterminal protein binds to the CAD enzyme at active sites of viral DNA replication on the nuclear matrix J. Virol., 72 (1998),pp. 2896-2904
[5]	Balasubramaniam, S., Duley, J., Christodoulou, J. Inborn errors of pyrimidine metabolism: clinical update and therapy J. Inherit. Metab. Dis., 37 (2014),pp. 687-698
[6]	Banerjee, D., Burkard, L., Panepinto, J.C. Inhibition of nucleotide biosynthesis potentiates the antifungal activity of amphotericin B PLoS One, 9 (2014),p. e87246
[7]	Bardeleben, C., Sharma, S., Reeve, J.R. et al. Metabolomics identifies pyrimidine starvation as the mechanism of 5-aminoimidazole-4-carboxamide-1-β-riboside-induced apoptosis in multiple myeloma cells Mol. Cancer Ther., 12 (2013),pp. 1310-1321
[8]	Barry, R.M., Bitbol, A., Lorestani, A. et al. Large-scale filament formation inhibits the activity of CTP synthetase eLife, 3 (2014),p. e03638
[9]	Ben-Sahra, I., Howell, J.J., Asara, J.M. et al. Science, 339 (2013),pp. 1323-1328
[10]	Carcamo, W.C., Calise, S.J., von Mühlen, C.A. et al. Molecular cell biology and immunobiology of mammalian rod/ring structures Int. Rev. Cell Mol. Biol., 308 (2014),pp. 35-74
[11]	Chauhan, M., Kumar, R. Medicinal attributes of pyrazolo[3,4-d]pyrimidines: a review Bioorg. Med. Chem., 21 (2013),pp. 5657-5668
[12]	Chen, C.T., Slocum, R.D. Plant Physiol. Biochem., 46 (2008),pp. 150-159
[13]	Chen, K., Zhang, J., Tastan, Ö.Y. et al. J. Genet. Genomics, 38 (2011),pp. 391-402
[14]	Christopherson, R.I., Jones, M.E. Interconversion of carbamayl-L-aspartate and L-dihydroorotate by dihydroorotase from mouse Ehrlich ascites carcinoma J. Biol. Chem., 254 (1979),pp. 12506-12512
[15]	Cox, R.A. Macromolecular structure and properties of ribonucleic acids Q. Rev. Chem. Soc., 22 (1968),pp. 499-526
[16]	De Gontijo, F.A., Pascon, R.C., Fernandes, L. et al. Fungal Genet. Biol., 70 (2014),pp. 12-23
[17]	Evans, D.R., Guy, H.I. Mammalian pyrimidine biosynthesis: fresh insights into an ancient pathway J. Biol. Chem., 279 (2004),pp. 33035-33038
[18]	Fox, B.A., Bzik, D.J. Nature, 415 (2002),pp. 926-929
[19]	Fox, B.A., Bzik, D.J. Infect. Immun., 78 (2010),pp. 3744-3752
[20]	García-Bayona, L., Garavito, M.F., Lozano, G.L. et al. Gene, 537 (2014),pp. 312-321
[21]	Geigenberger, P., Regierer, B., Nunes-Nesi, A. et al. Plant Cell, 17 (2005),pp. 2077-2088
[22]	Hortua Triana, M.A., Huynh, M.H., Garavito, M.F. et al. Mol. Biochem. Parasitol., 184 (2012),pp. 71-81
[23]	Hu, J., Locasale, J.W., Bielas, J.H. et al. Heterogeneity of tumor-induced gene expression changes in the human metabolic network Nat. Biotechnol., 31 (2013),pp. 522-529
[24]	Huang, M., Graves, L.M. Cell. Mol. Life Sci., 60 (2003),pp. 321-336
[25]	Hyde, J.E. Targeting purine and pyrimidine metabolism in human apicomplexan parasites Curr. Drug Targets, 8 (2007),pp. 31-47
[26]	Jain, K.S., Chitre, T.S., Miniyar, P.B. et al. Biological and medicinal significance of pyrimidines Curr. Sci., 90 (2006),pp. 793-803
[27]	Jones, M.E. Pyrimidine nucleotide biosynthesis in animals: genes, enzymes, and regulation of UMP biosynthesis Annu. Rev. Biochem., 49 (1980),pp. 253-279
[28]	Jung, E.J., Kwon, S.W., Jung, B.H. et al. Role of the AMPK/SREBP-1 pathway in the development of orotic acid-induced fatty liver J. Lipid Res., 52 (2011),pp. 1617-1625
[29]	Jung, E.J., Lee, K.Y., Lee, B.H. Proliferating effect of orotic acid through mTORC1 activation mediated by negative regulation of AMPK in SK-Hep1 hepatocellular carcinoma cells J. Toxicol. Sci., 37 (2012),pp. 813-821
[30]	Katahira, R., Ashihara, H. Physiol. Plant, 127 (2006),pp. 38-43
[31]	Ke, H., Morrisey, J.M., Ganesan, S.M. et al. Eukaryot. Cell, 10 (2011),pp. 1053-1061
[32]	Kusch, H., Engelmann, S., Bode, R. et al. Int. J. Med. Microbiol., 298 (2008),pp. 291-318
[33]	Le, T.T., Ziemba, A., Urasaki, Y. et al. Disruption of uridine homeostasis links liver pyrimidine metabolism to lipid accumulation J. Lipid Res., 54 (2013),pp. 1044-1057
[34]	Liu, J.L. The enigmatic cytoophidium: compartmentation of CTP synthase via filament formation Bioessays, 33 (2011),pp. 159-164
[35]	Loh, K.D., Gyaneshwar, P., Markenscoff Papadimitriou, E. et al. A previously undescribed pathway for pyrimidine catabolism Proc. Natl. Acad. Sci. USA, 103 (2006),pp. 5114-5119
[36]	Merry, A., Qiao, M., Hasler, M. et al. Biochem. J, 458 (2014),pp. 343-353
[37]	Munger, J., Bajad, S.U., Coller, H.A. et al. Dynamics of the cellular metabolome during human cytomegalovirus infection PLoS Pathog., 2 (2006),p. e132
[38]	Nara, T., Hshimoto, T., Aoki, T. Evolutionary implications of the mosaic pyrimidine-biosynthetic pathway in eukaryotes Gene, 257 (2000),pp. 209-222
[39]	Olszewski, K.L., Morrisey, J.M., Wilinski, D. et al. Cell Host Microbe, 5 (2009),pp. 191-199
[40]	Ong, H.B., Sienkiewicz, N., Wyllie, S. et al. Mol. Microbiol., 90 (2013),pp. 443-455
[41]	Painter, H.J., Morrisey, J.M., Mather, M.W. et al. Nature, 446 (2007),pp. 88-91
[42]	Patel, B.N., West, T.P. FEMS Microbiol. Lett., 40 (1987),pp. 33-36
[43]	Pfefferkorn, E.R., Pfefferkorn, L.C. J. Parasitol., 65 (1979),pp. 364-370
[44]	Poirier, S., Samami, S., Mamarbachi, M. et al. The epigenetic drug 5-azacytidine interferes with cholesterol and lipid metabolism J. Biol. Chem., 289 (2014),pp. 18736-18751
[45]	Robitaille, A.M., Christen, S., Shimobayashi, M. et al. Science, 339 (2013),pp. 1320-1323
[46]	Sahoo, S., Aurich, M.K., Jonsson, J.J. et al. Membrane transporters in a human genome-scale metabolic knowledgebase and their implications for disease Front. Physiol., 5 (2014),p. 91
[47]	Schröder, M., Giermann, N., Zrenner, R. Plant Physiol., 138 (2005),pp. 1926-1938
[48]	Sharma, V., Chitranshi, N., Agarwal, A.K. Significance and biological importance of pyrimidine in the microbial world Int. J. Med. Chem., 2014 (2014),p. 202784
[49]	Shock, J.L., Fischer, K.F., DeRisi, J.L. Genome Biol., 8 (2007),p. R134
[50]	Sigoillot, F.D., Berkowski, J.A., Sigoillot, S.M. et al. Cell cycle-dependent regulation of pyrimidine biosynthesis J. Biol. Chem., 278 (2003),pp. 3403-3409
[51]	Sreedharan, S., Shaik, J.H.A., Olszewski, P.K. et al. Glutamate, aspartate and nucleotide transporters in the SLC17 family form four main phylogenetic clusters: evolution and tissue expression BMC Genomics, 11 (2010),p. 17
[52]	Stasolla, C., Loukanina, N., Yeung, E.C. et al. Alterations in pyrimidine nucleotide metabolism as an early signal during the execution of programmed cell death in tobacco BY-2 cells J. Exp. Bot., 55 (2004),pp. 2513-2522
[53]	Tiedje, K.E., Stevens, K., Barnes, S. et al. Beta-alanine as a small molecule neurotransmitter Neurochem. Int., 57 (2010),pp. 177-188
[54]	Urasaki, Y., Pizzorno, G., Le, T.T. Uridine affects liver protein glycosylation, insulin signaling, and heme biosynthesis PLoS One, 9 (2014),p. e99728
[55]	Vastag, L., Koyuncu, E., Grady, S.L. et al. Divergent effects of human cytomegalovirus and herpes simplex virus-1 on cellular metabolism PLoS Pathog., 7 (2011),p. e1002124
[56]	Vogels, G., van der Drift, C. Degradation of purines and pyrimidines by microorganisms Bacteriol. Rev., 40 (1976),pp. 403-468
[57]	Webb, M.E., Smith, A.G., Abell, C. Biosynthesis of pantothenate Nat. Prod. Rep., 21 (2004),pp. 695-721
[58]	Zameitat, E., Freymark, G., Dietz, C.D. et al. Appl. Environ. Microbiol., 73 (2007),pp. 3371-3379

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doi: 10.1016/j.jgg.2015.04.004

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Pyrimidine Metabolism: Dynamic and Versatile Pathways in Pathogens and Cellular Development

Corresponding author: E-mail address: bhzimmermann@bhzonline.net (Barbara H. Zimmermann)

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doi: 10.1016/j.jgg.2015.04.004

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Pyrimidine Metabolism: Dynamic and Versatile Pathways in Pathogens and Cellular Development

Corresponding author: E-mail address: bhzimmermann@bhzonline.net (Barbara H. Zimmermann)

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出版历程

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