pyrimidine nucleobase biosynthetic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of pyrimidine nucleobases, 1,3-diazine, organic nitrogenous bases. [GOC:go_curators]

The pyrimidine nucleobase biosynthetic process is a fundamental pathway in all living organisms that produces the essential building blocks of DNA and RNA: cytosine, uracil, and thymine. This process is essential for cell growth, replication, and repair. The synthesis starts with the formation of carbamoyl phosphate from glutamine and carbon dioxide in the first committed step, catalyzed by carbamoyl phosphate synthetase II (CPS II). This molecule then reacts with aspartate to form carbamoyl aspartate, which is subsequently converted to dihydroorotate by dihydroorotase. Dihydroorotate is then oxidized to orotate by dihydroorotate dehydrogenase. Orotate is then activated by the addition of a phosphoribosyl group from PRPP (5'-phosphoribosyl-1-pyrophosphate) to form orotidine-5'-monophosphate (OMP) by orotate phosphoribosyltransferase. The final step in the pathway is the decarboxylation of OMP to uridine-5'-monophosphate (UMP) by orotidine 5'-phosphate decarboxylase. From UMP, the other pyrimidine nucleotides, cytidine triphosphate (CTP) and thymidine triphosphate (TTP), are synthesized. UMP is phosphorylated to UDP and then UTP. UTP is then aminated by CTP synthetase to form CTP. Thymine is derived from uracil by a series of reactions that involve the methylation of deoxyuridine monophosphate (dUMP) to thymidine monophosphate (dTMP) by thymidylate synthase, using dihydrofolate as a cofactor. The overall process is highly regulated by the availability of substrates, the activity of the enzymes involved, and the feedback inhibition of the pathway by the end products. Disruptions in pyrimidine biosynthesis can lead to severe health consequences including immunodeficiency, anemia, and neurodevelopmental disorders.'
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Proteins (1)

Compounds (4)