MetaCyc Pathway: superpathway of pyrimidine ribonucleotides de novo biosynthesis
Traceable author statement to experimental support

Enzyme View:

Pathway diagram: superpathway of pyrimidine ribonucleotides de novo biosynthesis

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: pyrimidine biosynthesis

Superclasses: BiosynthesisNucleosides and Nucleotides BiosynthesisPyrimidine Nucleotide BiosynthesisPyrimidine Nucleotides De Novo BiosynthesisPyrimidine Ribonucleotides De Novo Biosynthesis

Some taxa known to possess this pathway include : Arabidopsis thaliana col, Escherichia coli K-12 substr. MG1655, Homo sapiens

Expected Taxonomic Range: Bacteria , Eukaryota

General Background

Pyrimidine and purine nucleoside triphosphates are the activated precursors of DNA and RNA. The pyrimidine deoxyribonucleoside triphosphates dCTP and dTTP are incorporated into DNA while the ribonucleoside triphosphates CTP and UTP are incorporated into RNA. In addition, their diphosphates form activated derivatives of other molecules, such as UDP-α-D-glucose, CMP-3-deoxy-β-D-manno-octulosonate and dTDP-α-D-fucopyranose, for use in biosynthesis of polysaccharides, glycoproteins and phospholipids [Zhou98a, Giermann02, Schroder05, Zrenner06].

In addition to de novo biosynthesis, salvage pathways reutilize exogenous free bases and nucleosides and some of the resulting pyrimidine nucleotides can enter the de novo biosynthesis pathways (see pyrimidine ribonucleosides salvage I, pyrimidine nucleobases salvage I and pyrimidine deoxyribonucleosides salvage). The de novo biosynthetic pathways consume relatively large amounts of high energy phosphate and reducing power, and thus organisms prefer to use salvage pathways when possible. However, the de novo biosynthetic pathways are necessary when exogenous precursors are limiting. In order to conserve resources, the de novo pathways are regulated both by allosteric enzymes and at the gene expression level. These essential, evolutionarily conserved biosynthetic and salvage pathways are found in both prokaryotes and eukaryotes.

The pyrimidine nucleotide de novo biosynthetic pathway derives in part from the central metabolic precursors oxaloacetate and D-ribose 5-phosphate. L-aspartate, a precursor of pyrimidine ribonucleotides, is derived from oxaloacetate, which is generated in the TCA cycle.

About This Pathway

The de novo biosynthesis of UMP appears to be one of the most ancient biochemical pathways as it is evolutionary conserved in all species. The pathway converts hydrogen carbonate, L-glutamine, L-aspartate and 5-phospho-α-D-ribose 1-diphosphate (PRPP) to UMP (UMP), a pyrimidine nucleotide that can be subsequently converted to all other pyrimidine nucleotides.

The enzyme UMP kinase catalyzes the phosphorylation of UMP to form UDP. The eukaryotic enzyme also catalyzes the phosphorylation of CMP to CDP, and was thus named UMP/CMP kinase [Okada04].

The penultimate enzyme in this pathway, nucleoside diphosphate kinase (NDK), catalyzes a reaction in which the terminal phosphate of a nucleoside triphosphate is transferred to a nucleoside diphosphate - in this case, the transfer of a phosphate from the purine ATP to the pyrimidine UDP, forming UTP. The enzyme has a broad substrate specificity, and is involved in the biosynthesis of several nucleoside-triphosphates, including formation of CTP from CDP.

Interconversion between thymidine and cytidine nucleotides is possible only at the level of nucleoside triphosphates, by the glutamine (or ammonia)-dependent enzyme CTP synthase.

Superpathways: superpathway of histidine, purine, and pyrimidine biosynthesis, superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis

Subpathways: UTP and CTP de novo biosynthesis, UMP biosynthesis

Unification Links: EcoCyc:PWY0-162

Martha Arnaud on Tue Jan 21, 2003:
This pathway supersedes the pathway formerly called "pyrimidine biosynthesis."

Created 23-Jan-2003 by Arnaud M, SRI International
Revised 24-Oct-2007 by Caspi R, SRI International
Revised 04-Jan-2013 by Caspi R, SRI International


Giermann02: Giermann N, Schroder M, Ritter T, Zrenner R (2002). "Molecular analysis of de novo pyrimidine synthesis in solanaceous species." Plant Mol Biol 50(3);393-403. PMID: 12369616

Okada04: Okada K, Ohara K, Yazaki K, Nozaki K, Uchida N, Kawamukai M, Nojiri H, Yamane H (2004). "The AtPPT1 gene encoding 4-hydroxybenzoate polyprenyl diphosphate transferase in ubiquinone biosynthesis is required for embryo development in Arabidopsis thaliana." Plant Mol Biol 55(4);567-77. PMID: 15604701

Schroder05: Schroder M, Giermann N, Zrenner R (2005). "Functional analysis of the pyrimidine de novo synthesis pathway in solanaceous species." Plant Physiol 138(4);1926-38. PMID: 16024685

Zhou98a: Zhou L, Lacroute F, Thornburg R (1998). "Cloning, expression in Escherichia coli, and characterization of Arabidopsis thaliana UMP/CMP kinase." Plant Physiol 117(1);245-54. PMID: 9576794

Zrenner06: Zrenner R, Stitt M, Sonnewald U, Boldt R (2006). "Pyrimidine and purine biosynthesis and degradation in plants." Annu Rev Plant Biol 57;805-36. PMID: 16669783

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Aghajari94: Aghajari N, Jensen KF, Gajhede M (1994). "Crystallization and preliminary X-ray diffraction studies on the Apo form of orotate phosphoribosyltransferase from Escherichia coli." J Mol Biol 241(2);292-4. PMID: 8057372

Alam04: Alam N, Stieglitz KA, Caban MD, Gourinath S, Tsuruta H, Kantrowitz ER (2004). "240s loop interactions stabilize the T state of Escherichia coli aspartate transcarbamoylase." J Biol Chem 279(22);23302-10. PMID: 15014067

Almaula95: Almaula N, Lu Q, Delgado J, Belkin S, Inouye M (1995). "Nucleoside diphosphate kinase from Escherichia coli." J Bacteriol 177(9);2524-9. PMID: 7730286

Andersen91: Andersen JT, Jensen KF, Poulsen P (1991). "Role of transcription pausing in the control of the pyrE attenuator in Escherichia coli." Mol Microbiol 5(2);327-33. PMID: 1710313

Anderson75: Anderson PM, Carlson JD (1975). "Reversible reaction of cyanate with a reactive sulfhydryl group at the glutamine binding site of carbamyl phosphate synthetase." Biochemistry 1975;14(16);3688-94. PMID: 240389

Anderson77: Anderson PM (1977). "Binding of allosteric effectors to carbamyl-phosphate synthetase from Escherichia coli." Biochemistry 1977;16(4);587-93. PMID: 189806

Anderson83: Anderson PM (1983). "CTP synthetase from Escherichia coli: an improved purification procedure and characterization of hysteretic and enzyme concentration effects on kinetic properties." Biochemistry 22(13);3285-92. PMID: 6349684

Andrews77: Andrews S, Cox GB, Gibson F (1977). "The anaerobic oxidation of dihydroorotate by Escherichia coli K-12." Biochim Biophys Acta 462(1);153-60. PMID: 199252

Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699

Backstrom86: Backstrom D, Sjoberg RM, Lundberg LG (1986). "Nucleotide sequence of the structural gene for dihydroorotase of Escherichia coli K12." Eur J Biochem 160(1);77-82. PMID: 2876892

Bairoch93: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

Bearne01: Bearne SL, Hekmat O, Macdonnell JE (2001). "Inhibition of Escherichia coli CTP synthase by glutamate gamma-semialdehyde and the role of the allosteric effector GTP in glutamine hydrolysis." Biochem J 356(Pt 1);223-32. PMID: 11336655

Begley00: Begley TP, Appleby TC, Ealick SE (2000). "The structural basis for the remarkable catalytic proficiency of orotidine 5'-monophosphate decarboxylase." Curr Opin Struct Biol 10(6);711-8. PMID: 11114509

Bennett04: Bennett SE, Chen CY, Mosbaugh DW (2004). "Escherichia coli nucleoside diphosphate kinase does not act as a uracil-processing DNA repair nuclease." Proc Natl Acad Sci U S A 101(17);6391-6. PMID: 15096615

Bernard00: Bernard MA, Ray NB, Olcott MC, Hendricks SP, Mathews CK (2000). "Metabolic functions of microbial nucleoside diphosphate kinases." J Bioenerg Biomembr 32(3);259-67. PMID: 11768309

Bjornberg01: Bjornberg O, Jordan DB, Palfey BA, Jensen KF (2001). "Dihydrooxonate is a substrate of dihydroorotate dehydrogenase (DHOD) providing evidence for involvement of cysteine and serine residues in base catalysis." Arch Biochem Biophys 391(2);286-94. PMID: 11437361

Bjornberg99: Bjornberg O, Gruner AC, Roepstorff P, Jensen KF (1999). "The activity of Escherichia coli dihydroorotate dehydrogenase is dependent on a conserved loop identified by sequence homology, mutagenesis, and limited proteolysis." Biochemistry 38(10);2899-908. PMID: 10074342

Bonekamp84: Bonekamp F, Clemmesen K, Karlstrom O, Jensen KF (1984). "Mechanism of UTP-modulated attenuation at the pyrE gene of Escherichia coli: an example of operon polarity control through the coupling of translation to transcription." EMBO J 3(12);2857-61. PMID: 6098450

Bonekamp85: Bonekamp F, Andersen HD, Christensen T, Jensen KF (1985). "Codon-defined ribosomal pausing in Escherichia coli detected by using the pyrE attenuator to probe the coupling between transcription and translation." Nucleic Acids Res 13(11);4113-23. PMID: 2989788

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 20.0 (software by SRI International) on Fri May 6, 2016, BIOCYC13A.