Skip to main content
Biology LibreTexts

7.10: Pyrimidine de novo Biosynthesis

  • Page ID
    3063
  • \( \newcommand{\vecs}[1]{\overset { \scriptstyle \rightharpoonup} {\mathbf{#1}} } \) \( \newcommand{\vecd}[1]{\overset{-\!-\!\rightharpoonup}{\vphantom{a}\smash {#1}}} \)\(\newcommand{\id}{\mathrm{id}}\) \( \newcommand{\Span}{\mathrm{span}}\) \( \newcommand{\kernel}{\mathrm{null}\,}\) \( \newcommand{\range}{\mathrm{range}\,}\) \( \newcommand{\RealPart}{\mathrm{Re}}\) \( \newcommand{\ImaginaryPart}{\mathrm{Im}}\) \( \newcommand{\Argument}{\mathrm{Arg}}\) \( \newcommand{\norm}[1]{\| #1 \|}\) \( \newcommand{\inner}[2]{\langle #1, #2 \rangle}\) \( \newcommand{\Span}{\mathrm{span}}\) \(\newcommand{\id}{\mathrm{id}}\) \( \newcommand{\Span}{\mathrm{span}}\) \( \newcommand{\kernel}{\mathrm{null}\,}\) \( \newcommand{\range}{\mathrm{range}\,}\) \( \newcommand{\RealPart}{\mathrm{Re}}\) \( \newcommand{\ImaginaryPart}{\mathrm{Im}}\) \( \newcommand{\Argument}{\mathrm{Arg}}\) \( \newcommand{\norm}[1]{\| #1 \|}\) \( \newcommand{\inner}[2]{\langle #1, #2 \rangle}\) \( \newcommand{\Span}{\mathrm{span}}\)\(\newcommand{\AA}{\unicode[.8,0]{x212B}}\)

    Starting materials for pyrimidine biosynthesis (Figure 7.10.1) include bicarbonate, amine from glutamine, and phosphate from ATP to make carbamoyl-phosphate (similar to the reaction of the urea cycle). Joining of carbamoyl phosphate to aspartic acid (forming carbamoyl aspartate) is catalyzed by the most important regulatory enzyme of the cycle, aspartate transcarbamoylase (also called aspartate carbamoyltransferase or ATCase).

    Figure 7.10.1.png
    Figure 7.10.1: De Novo Synthesis of Pyrimidine Nucleotides

    ATCase is regulated by three compounds. One of these (aspartate) is a substrate and it activates the enzyme by binding to the catalytic site and favoring the enzyme’s R state. The other two regulators bind to regulatory subunits of the enzyme and either inhibit (CTP) or activate (ATP) the enzyme.

    The reaction product, carbamoyl aspartate, is transformed in two reactions to orotic acid, which is, in turn combined with phosphoribosylpyrophosphate PRPP). The product of that reaction, orotidyl monophosphate (OMP) is decarboxylated to form the first pyrimidine nucleotide, UMP. Conversion of UMP to UDP is catalyzed by nucleoside monophosphate kinases (NMPs) and UDP is converted to UTP by nucleoside diphosphokinase (NDPK).

    UDP (like all of the nucleoside diphosphates) is a branch point to deoxyribonucleoside diphosphates, catalyzed by ribonucleotide reductases, which are discussed later. UTP is converted to CTP by CTP synthase. This enzyme, which uses an amino group from glutamine for the reaction, serves to balance the relative amounts of CTP and UTP, thanks to inhibition by excess CTP.


    This page titled 7.10: Pyrimidine de novo Biosynthesis is shared under a CC BY-NC-SA 4.0 license and was authored, remixed, and/or curated by Kevin Ahern & Indira Rajagopal via source content that was edited to the style and standards of the LibreTexts platform; a detailed edit history is available upon request.