Pyrimidine biosynthesis

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Pyrimidine biosynthesis occurs both in the body and through organic synthesis.

Contents

Unlike purines, pyrimidines are assembled before being attached to 5-phosphoribosyl-1-pyrophosphate (PRPP).

  • Dihydroorotate then enters the mitochondria where it is oxidised through removal of hydrogens to form orotate. This is the only mitochondrial step in nucleotide rings biosynthesis. The enzyme involved is dihydroorotate dehydrogenase (the only mitochondrial enzyme).
  • Once orotate is eventually formed, it is combined with PRPP to form orotidine 5' -monophosphate (OMP) which is decarboxylated in a reaction catalysed by OMP decarboxylase to form uridine 5'-monophosphate.[citation needed]
  • UMP is then converted to UDP catalysed by nucleotide diphosphokinase which is further phosphorylated to UTP by CTP synthase. This later reaction eventually leads to the formation of cytidine 5'triphosphate and glutamine is utilized.[citation needed]

Pyrimidines are ultimately catabolized (degraded) to CO2, H2O, and urea. Cytosine can be broken down to uracil which can be further broken down to N-carbamoyl-β-alanine. Thymine is broken down into β-aminoisobutyrate which can be further broken down into intermediates eventually leading into the citric acid cycle. β-aminoisobutyrate acts as a rough indicator for rate of DNA turnover.[citation needed]

Pyrimidines can also be prepared in the laboratory by organic synthesis. Many methods rely on condensation of carbonyls with amines for instance the synthesis of 2-Thio-6-methyluracil from thiourea and ethyl acetoacetate [1] or the synthesis of 4-methylpyrimidine with 4,4-dimethoxy-2-butanone and formamide [2].

A novel method is by reaction of certain amides with carbonitriles under electrophilic activation of the amide with 2-chloro-pyridine and trifluoromethanesulfonic anhydride [3]:

Pyrimidine Synthesis Movassaghi 2006


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