Pyrimidines are heterocyclic aromatic organic compounds. These nitrogenous bases form an essential part of nucleic acids in DNA and RNA. Cytosine and thymine are inserted into the structure of DNA, while RNA utilizes cytosine and uracil. In metabolism, the pyrimidine is usually cleaved and the end products are typically beta-amino acids, ammonia and carbon dioxide. Pyrimidine metabolism in Arabidopsis thaliana occurs mostly in the nucleus, cytosol and chloroplast of the cell, with a few reactions taking place in the mitochondria, ER, vacuole, plasma membrane and peroxisome. The pyrimidines are incorporated into DNA in the compounds dTTP and dCTP. The apyrase enzyme or nucleoside diphosphate kinase-1 can convert dTTP to dTDP. Apyrase or thymidylate kinase can then convert dTDP to dTMP. Nucleotide diphosphatase can also metabolize dTTP directly to dTMP. The enzyme 5’-nucleotidase converts dTMP to thymidine. An unknown enzyme then metabolizes thymidine to thymine. Thymine is converted into dihydrothymine by dihydropyrimidine dehydrogenase. Dihydropyrimidinase converts dihydrothymine to 3-ureidoisobutyrate, which then forms 3-aminoisobutyrate via beta-ureidopropionase. Nucleotide diphosphate kinase-1 converts dCTP into dCDP, which produces dCMP via the enzyme UMP-CMP kinase-1. Two unknown enzymes metabolize dCMP to 2'-deoxy-5-hydroxymethylcytidine-5'-diphosphate which is then converted to 2'-deoxy-5-hydroxymethylcytidine-5’-triphosphate by nucleotide diphosphate kinase-1. Deoxycytidine is formed from dCMP by 5’-nucleotidase and is converted to deoxyuridine via cytidine deaminase. Thymidine kinase converts deoxyuridine to dUMP. The compound dUMP can also be formed from dCMP using dCMP deaminase. The dUMP formed is converted into dTMP by bifunctional dihydrofolate reductase-thymidylate synthase-1. The dTMP follows the metabolism pathway as previously mentioned to eventually form 3-aminoisobutyrate.
The pyrimidines are incorporated into RNA in the compounds UTP and CTP. UTP is metabolised to UDP using the enzyme apyrase or nucleoside disphosphate kinase-1. UDP then forms UMP via apyrase or via the enzymes UMP-CMP kinase-1 and uridylate kinase. UMP can be directly formed from UTP using nucleotide diphosphatase. Uridine is produced from metabolism of UMP by the enzyme 5’-nucleotidase. Uridine nucleosidase-1 then forms uracil from uridine. Uracil phosphoribosyltransferase can also create uracil directly from UMP. Dihydrouracil is made from uracil via dihydropyrimidine dehydrogenase. Dihydropyrimidinase converts dihydrouracil to 3-ureidopropionate. Finally, β-alanine is generated from 3-ureidopropionate through the enzyme Beta-ureidopropionase.
UTP can be converted into CTP via CTP synthase. CTP is then converted into CDP via apyrase or nucleoside disphosphate kinase-1. CDP forms dCDP via ribonucleoside-diphosphate reductase. The dCDP follows the metabolism pathway as previously mentioned, forming 3-aminoisobutyrate. CDP can also form CMP via apyrase or UMP-CMP kinase-1. CMP can be directly produced from CTP using nucleotide diphosphatase. Cytidine is then generated from the metabolism of CMP by 5’-nucleotidase. The cytidine formed can then be metabolized into uracil via cytidine deaminase. Uridine then follows the same metabolism pathway as previously mentioned to eventually form β-alanine.
References
Pyrimidine Metabolism References
National Center for Biotechnology Information. PubChem Database. Pyrimidine, CID=9260, https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine (accessed on July 6, 2020)
Angstadt, C. (1997). Purine and pyrimidine metabolism. NetBiochem.
Retrieved from: https://library.med.utah.edu/NetBiochem/NetWelco.htm
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