conversion of dUMP to dTMP dUTP + H2O => dUMP + pyrophosphate dCMP + H2O => dUMP + NH4+ phosphoribosylation of orotate to form oritidine 5'-phosphate (OMP) orotidine 5'-monophosphate => uridine 5'-monophosphate + CO2 N-carbamoyl L-aspartate + H+ <=> (S)-dihydroorotate + H2O oxidation of (S)-Dihydroorotate to form Orotate bicarbonate and glutamine combine to form carbamoyl phosphate carbamoyl phosphate and L-aspartate combine to form N-Carbamoyl-L-aspartate PathwayStep2244 PathwayStep2243 PathwayStep2250 PathwayStep2251 PathwayStep2248 PathwayStep2247 PathwayStep2246 PathwayStep2245 PathwayStep2249 Pyrimidine biosynthesis Authored: D'Eustachio, P, 2010-02-05 Edited: D'Eustachio, P, 2010-02-18 GENE ONTOLOGYGO:0046134 ISBN0079130356 Pubmed6105839 Reactome Database ID Release 43500753 Reactome, http://www.reactome.org ReactomeREACT_21376 Reviewed: Graves, L, Rush, MG, 0000-00-00 00:00:00 The pyrimidine orotate (orotic acid) is synthesized in a sequence of four reactions, deriving its atoms from glutamine, bicarbonate, and aspartate. A single multifunctional cytosolic enzyme catalyzes the first three of these reactions, while the last one is catalyzed by an enzyme associated with the inner mitochondrial membrane. In two further reactions, catalyzed by a bifunctional cytosolic enzyme, orotate reacts with 1-phosphoribosyl 5-pyrophosphate (PRPP) to yield orotidine 5'-monophosphate, which is decarboxylated to yield uridine 5'-monophosphate (UMP). While several individual reactions in this pathway are reversible, other irreversible reactions drive the pathway in the direction of UMP biosynthesis in the normal cell. All reactions are thus annotated here only in the forward direction.<P>This pathway has been most extensively analyzed at the genetic and biochemical level in hamster cell lines. All three enzymes have also been purified from human sources, however, and the key features of these reactions have been confirmed from studies of this human material (Jones 1980; Webster et al. 2001).<p>All other pyrimidines are synthesized from UMP. The reactions annotaed here, catalyzed by dCMP deaminase and dUTP diphosphatase yield dUMP, which in turn is converted to TMP by thymidylate synthase.