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. 2014 May 3;13:63. doi: 10.1186/1475-2859-13-63

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Copyright © 2014 Dong and Zhang; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Summary of pyrimidine metabolism pathway and mechanisms of action of pyrimidine analogs. Orotate is metabolized to UMP by OPRTase and OMPdecase, encoded by pyrE and pyrF, respectively. These enzymes also convert 5-fluoroorotate to 5-fluoro-UMP. pyrR encodes an mRNA-binding attenuator (PyrR) that negatively regulates pyr expression by sensing UMP or UTP. UMP is also produced from uracil by UPRTase, encoded by upp. UPRTase converts 5-FU to 5-fluoro-UMP, which is further metabolized to the toxic metabolite 5-fluoro-dUMP. 5-fluoro-dUMP is a strong inhibitor of thymidylate synthetase, which provides the sole de novo source of dTMP for DNA biosynthesis.