Pyrimidine Biosynthetic Pathway
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Pyrimidine Biosynthetic Pathway
Pyrimidine biosynthesis occurs both in the body and through organic synthesis. ''De novo'' biosynthesis of pyrimidine ''De Novo'' biosynthesis of a pyrimidine is catalyzed by three gene products CAD, DHODH and UMPS. The first three enzymes of the process are all coded by the same gene in CAD (protein), CAD which consists of Carbamoyl phosphate synthase II, carbamoyl phosphate synthetase II, aspartate carbamoyltransferase and dihydroorotase. Dihydroorotate dehydrogenase, Dihydroorotate dehydrogenase (DHODH) unlike CAD (protein), CAD and Uridine monophosphate synthetase, UMPS is a mono-functional enzyme and is localized in the mitochondria. UMPS is a bifunctional enzyme consisting of Orotate phosphoribosyltransferase, orotate phosphoribosyltransferase (OPRT) and Orotidine 5'-phosphate decarboxylase, orotidine monophosphate decarboxylase (OMPDC). Both, CAD and UMPS are localized around the mitochondria, in the cytosol. In Fungi, a similar protein exists but lacks the dihydroorotase ...
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Carbamoyl Phosphate Synthetase II
Carbamoyl phosphate synthetase (glutamine-hydrolysing) () is an enzyme that catalyzes the reactions that produce carbamoyl phosphate in the cytosol (as opposed to type I, which functions in the mitochondria). Its systemic name is ''hydrogen-carbonate:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating)''. In pyrimidine biosynthesis, it serves as the rate-limiting enzyme and catalyzes the following reaction: : 2 ATP + L-glutamine + HCO3− + H2O \rightleftharpoons 2 ADP + phosphate + L-glutamate + carbamoyl phosphate (overall reaction) : (1a) L-glutamine + H2O \rightleftharpoons L-glutamate + NH3 : (1b) 2 ATP + HCO3− + NH3 \rightleftharpoons 2 ADP + phosphate + carbamoyl phosphate It is activated by ATP and PRPP and it is inhibited by UMP (Uridine monophosphate, the end product of the pyrimidine synthesis pathway). Neither CPSI nor CPSII require biotin as a coenzyme, as seen with most carboxylation reactions. It is one of the three enzyme functions coded by the CA ...
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