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Escherichia coli K-12 substr. MG1655 Pathway: UMP biosynthesis

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Genetic Regulation Schematic: ?

Synonyms: uridine-5'-phosphate biosynthesis, de novo biosynthesis of uridine-5'-phosphate, de novo biosynthesis of uridine-5'-monophosphate

Superclasses: Biosynthesis Nucleosides and Nucleotides Biosynthesis Pyrimidine Nucleotide Biosynthesis Pyrimidine Nucleotides De Novo Biosynthesis Pyrimidine Ribonucleotides De Novo Biosynthesis

Summary:
General Background

Pyrimidine and purine nucleotides are components of nucleic acids in all living organisms. Although the enzymatic steps in their de novo biosynthesis are conserved, some differences in the enzymes exist. For example in bacteria and plants the three steps leading from carbamoyl phosphate to orotate are catalyzed by three different proteins, while in mammals they are catalyzed by a single multifunctional CAD protein. In plants and animals the last two steps of the pathway are catalyzed by the bifunctional enzyme UMP synthase, whereas bacteria express two separate proteins for this purpose (in [Iwahana96, Giermann02] and reviewed in [Zrenner06].

About This Pathway

The de novo pyrimidine nucleotide biosynthetic pathway converts bicarbonate, L-glutamine, L-aspartate and 5-phospho-α-D-ribose 1-diphosphate (PRPP) to uridine 5'-phosphate (UMP), a pyrimidine ribonucleotide that can be subsequently converted to other pyrimidine ribonucleotides as shown in the link at the end of this pathway, and in the superpathway links below.

The first enzyme, carbamoyl phosphate synthetase, forms carbamoyl phosphate from ATP, bicarbonate, and ammonia derived from L-glutamine. Carbamoyl phosphate is both an intermediate of pyrimidine synthesis and also a precursor for the synthesis of amino acids such as L-arginine and L-citrulline as shown in the pathway link, and L-canavanine in plants [Cronk06].

The next step, which is catalyzed by aspartate transcarbamylase, is the condensation of carbamoyl phosphate with L-aspartate forming N-carbamoyl-L-aspartate. This is the committed step in pyrimidine nucleotide biosynthesis. N-carbamoyl-L-aspartate, is then cyclized to (S)-dihydroorotate, the first intermediate that contains a pyrimidine ring. This compound is oxidized to orotate by dihydroorotate dehydrogenase. Orotate, an aromatic pyrimidine base, is therefore formed in three steps from carbamoyl phosphate.

The final two steps, the condensation of orotate with PRPP forming the first pyrimidine nucleotide orotidine 5'-phosphate (OMP), followed by the decarboylation of OMP to UMP, are carried out by the enzymes orotate phosphoribosyltransferase and orotidine 5'-phosphate decarboxylase. UMP was identified in early work as an inhibitor of the first enzyme carbamoyl phosphate synthase [Trotta74].

In enteric bacteria the pyrimidine biosynthetic genes are scattered on the chromosome and may be a single transcriptional unit or part of a small operon. They have their own regulatory mechanisms and are not regulated by a common repressor.

Review: Jensen, K.F., G. Dandanell, B. Hove-Jensen and M. Willemoes (2008) "Nucleotides, Nucleosides and Nucleobases" EcoSal 3.6.2 [ECOSAL]

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

Credits:
Created 24-Oct-2007 by Caspi R , SRI International
Reviewed 24-Oct-2007 by Foerster H , TAIR
Revised 24-Dec-2008 by Caspi R , SRI International
Last-Curated ? 03-Jun-2011 by Fulcher C , SRI International


References

Cronk06: Cronk Q, Ojeda I, Pennington RT (2006). "Legume comparative genomics: progress in phylogenetics and phylogenomics." Curr Opin Plant Biol 9(2);99-103. PMID: 16480916

ECOSAL: "Escherichia coli and Salmonella: Cellular and Molecular Biology." Online edition.

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

Iwahana96: Iwahana H, Fujimura M, Ii S, Kondo M, Moritani M, Takahashi Y, Yamaoka T, Yoshimoto K, Itakura M (1996). "Molecular cloning of a human cDNA encoding a trifunctional enzyme of carbamoyl-phosphate synthetase-aspartate transcarbamoylase-dihydroorotase in de Novo pyrimidine synthesis." Biochem Biophys Res Commun 219(1);249-55. PMID: 8619816

Trotta74: Trotta PP, Pinkus LM, Haschemeyer RH, Meister A (1974). "Reversible dissociation of the monomer of glutamine-dependent carbamyl phosphate synthetase into catalytically active heavy and light subunits." J Biol Chem 1974;249(2);492-9. PMID: 4358555

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

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

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

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

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." http://www.brenda-enzymes.org.

Brown91: Brown DC, Collins KD (1991). "Dihydroorotase from Escherichia coli. Substitution of Co(II) for the active site Zn(II)." J Biol Chem 1991;266(3);1597-604. PMID: 1671037

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

Callahan07: Callahan BP, Miller BG (2007). "OMP decarboxylase--An enigma persists." Bioorg Chem 35(6);465-9. PMID: 17889251

Changeux68: Changeux JP, Gerhart JC, Schachman HK (1968). "Allosteric interactions in aspartate transcarbamylase. I. Binding of specific ligands to the native enzyme and its isolated subunits." Biochemistry 7(2);531-8. PMID: 4868539

Christopherson78: Christopherson RI, Finch LR (1978). "Response of the pyrimidine pathway of Escherichia coli K 12 to exogenous adenine and uracil." Eur J Biochem 90(2);347-58. PMID: 361403

Collins71: Collins KD, Stark GR (1971). "Aspartate transcarbamylase. Interaction with the transition state analogue N-(phosphonacetyl)-L-aspartate." J Biol Chem 1971;246(21);6599-605. PMID: 4943676

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Wed Dec 17, 2014, BIOCYC13B.