Editing Nucleotide (section)

===Pyrimidine ribonucleotide synthesis===
[[File:Nucleotides syn2.png|thumb|right|400px|The synthesis of [[Uridine monophosphate|UMP]].
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{{legend|rgb(227,13,196)|metal ions}}
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{{main|Pyrimidine metabolism}}
The synthesis of the pyrimidines CTP and UTP occurs in the cytoplasm and starts with the formation of carbamoyl phosphate from [[glutamine]] and CO<sub>2</sub>. Next, [[aspartate carbamoyltransferase]] catalyzes a condensation reaction between [[aspartate]] and [[carbamoyl phosphate]] to form [[carbamoyl aspartic acid]], which is cyclized into [[4,5-dihydroorotic acid]] by [[dihydroorotase]]. The latter is converted to [[orotate]] by [[dihydroorotate oxidase]]. The net reaction is:

:(''S'')-Dihydroorotate + O<sub>2</sub> → Orotate + H<sub>2</sub>O<sub>2</sub>

Orotate is covalently linked with a phosphorylated ribosyl unit. The covalent linkage between the ribose and pyrimidine occurs at position C<sub>1</sub><ref>See [[IUPAC nomenclature of organic chemistry]] for details on carbon residue numbering</ref> of the [[ribose]] unit, which contains a [[pyrophosphate]], and N<sub>1</sub> of the pyrimidine ring. [[Orotate phosphoribosyltransferase]] (PRPP transferase) catalyzes the net reaction yielding orotidine monophosphate (OMP):

:Orotate + [[Phosphoribosyl pyrophosphate|5-Phospho-α-D-ribose 1-diphosphate (PRPP)]]  →  Orotidine 5'-phosphate + Pyrophosphate

[[Orotidine 5'-monophosphate]] is decarboxylated by orotidine-5'-phosphate decarboxylase to form uridine monophosphate (UMP). PRPP transferase catalyzes both the ribosylation and decarboxylation reactions, forming UMP from orotic acid in the presence of PRPP. It is from UMP that other pyrimidine nucleotides are derived.  UMP is phosphorylated by two kinases to uridine triphosphate (UTP) via two sequential reactions with ATP.  First, the diphosphate from UDP is produced, which in turn is phosphorylated to UTP. Both steps are fueled by ATP hydrolysis:

:ATP + UMP → ADP + UDP

:UDP + ATP → UTP + ADP

CTP is subsequently formed by the amination of UTP by the catalytic activity of [[CTP synthetase]]. Glutamine is the NH<sub>3</sub> donor and the reaction is fueled by ATP hydrolysis, too:

:UTP + Glutamine + ATP + H<sub>2</sub>O → CTP + ADP + P<sub>i</sub>

Cytidine monophosphate (CMP) is derived from cytidine triphosphate (CTP) with subsequent loss of two phosphates.<ref>{{cite journal | vauthors = Jones ME | title = Pyrimidine nucleotide biosynthesis in animals: genes, enzymes, and regulation of UMP biosynthesis | journal = Annual Review of Biochemistry | volume = 49 | issue = 1 | pages = 253–79 | date = 1980 | pmid = 6105839 | doi = 10.1146/annurev.bi.49.070180.001345 }}</ref><ref>{{cite book |title=The organic chemistry of biological pathways |vauthors=McMurry JE, Begley TP |date=2005 |publisher=Roberts & Company |isbn=978-0-9747077-1-6}}
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