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MetaCyc Pathway: superpathway of purine nucleotides de novo biosynthesis II

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

Superclasses: Biosynthesis Nucleosides and Nucleotides Biosynthesis Purine Nucleotide Biosynthesis Purine Nucleotides De Novo Biosynthesis

Some taxa known to possess this pathway include ? : Escherichia coli K-12 substr. MG1655 , Salmonella enterica enterica serovar Typhimurium

Expected Taxonomic Range: Bacteria

Purine nucleotides participate in many aspects of cellular metabolism including the structure of DNA and RNA, serving as enzyme cofactors, functioning in cellular signaling, acting as phosphate group donors, and generating cellular energy. Maintenance of the proper balance of intracellular pools of these nucleotides is critical to normal function. This occurs through a combination of de novo biosynthesis and salvage pathways for pre-existing purine bases, nucleosides and nucleotides.

The de novo biosynthetic pathway for purine nucleotides is highly conserved among organisms, but its regulation and the organization of the genes encoding the enzymes vary. This fourteen step pathway contains ten steps that branch at IMP to form AMP and GMP, each in two steps. Regulation of the pathway has been well studied in microbes such as Escherichia coli, Bacillus subtilis and Saccharomyces cerevisiae, but little is known about its regulation in higher eukaryotes (metazoa, and plants [Senecoff96]). The pathway appears to vary in archaea [White97]. Some organisms, such as the mycoplasmas, do not biosynthesize purine and pyrimidine bases de novo and must rely on salvage pathways [Wang01].

In bacterial systems genetic studies indicate that the majority of de novo purine biosynthetic genes are unlinked but may act as a single unit of regulation controlled by the PurR transcriptional repressor protein. In Escherichia coli the 14 reactions involved in the de novo synthesis of AMP and GMP are catalyzed by 12 known genes. These genes occur mostly as unlinked single units or as small functional operons carrying two or, at the most, three structural genes each. The purR gene encodes the repressor controlling the synthesis of all of these enzymes. Sequences similar to the protected region (PUR box) in purF are present in the regulatory regions of purMN. The expression of purR was shown to be autoregulated, probably through blocking of transcription elongation by binding of PurR to the two PUR boxes. So far, six genes/operons have been reported to contain PUR box-like sequences. The purine biosynthetic pathway is controlled by feedback regulation of activity as well as at the level of transcription [Meng90].

Reactions that convert ADP to ATP are found in multiple pathways, including fueling pathways such as anaerobic respiration, TCA-aerobic respiration, fermentation, and glycolysis, and are thus not included in this pathway.

Superpathways: superpathway of histidine, purine, and pyrimidine biosynthesis

Subpathways: guanosine ribonucleotides de novo biosynthesis , guanosine deoxyribonucleotides de novo biosynthesis II , superpathway of guanosine nucleotides de novo biosynthesis II , superpathway of adenosine nucleotides de novo biosynthesis II , inosine-5'-phosphate biosynthesis I , 5-aminoimidazole ribonucleotide biosynthesis II , adenosine deoxyribonucleotides de novo biosynthesis II , adenosine ribonucleotides de novo biosynthesis

Variants: superpathway of adenosine nucleotides de novo biosynthesis I , superpathway of guanosine nucleotides de novo biosynthesis I , superpathway of purine nucleotides de novo biosynthesis I

Unification Links: EcoCyc:DENOVOPURINE2-PWY

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

Created 17-Dec-2002 by Arnaud M , SRI International


Meng90: Meng LM, Kilstrup M, Nygaard P (1990). "Autoregulation of PurR repressor synthesis and involvement of purR in the regulation of purB, purC, purL, purMN and guaBA expression in Escherichia coli." Eur J Biochem 1990;187(2);373-9. PMID: 2404765

Neidhardt96: Neidhardt FC, Curtiss III R, Ingraham JL, Lin ECC, Low Jr KB, Magasanik B, Reznikoff WS, Riley M, Schaechter M, Umbarger HE "Escherichia coli and Salmonella, Cellular and Molecular Biology, Second Edition." American Society for Microbiology, Washington, D.C., 1996.

Senecoff96: Senecoff JF, McKinney EC, Meagher RB (1996). "De novo purine synthesis in Arabidopsis thaliana. II. The PUR7 gene encoding 5'-phosphoribosyl-4-(N-succinocarboxamide)-5-aminoimidazole synthetase is expressed in rapidly dividing tissues." Plant Physiol 112(3);905-17. PMID: 8938402

Wang01: Wang L, Westberg J, Bolske G, Eriksson S (2001). "Novel deoxynucleoside-phosphorylating enzymes in mycoplasmas: evidence for efficient utilization of deoxynucleosides." Mol Microbiol 42(4);1065-73. PMID: 11737647

White97: White RH (1997). "Purine biosynthesis in the domain Archaea without folates or modified folates." J Bacteriol 179(10);3374-7. PMID: 9150241

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

Abbott06: Abbott JL, Newell JM, Lightcap CM, Olanich ME, Loughlin DT, Weller MA, Lam G, Pollack S, Patton WA (2006). "The Effects of Removing the GAT Domain from E. coli GMP Synthetase." Protein J 25;483-491. PMID: 17103135

Aiba89: Aiba A, Mizobuchi K (1989). "Nucleotide sequence analysis of genes purH and purD involved in the de novo purine nucleotide biosynthesis of Escherichia coli." J Biol Chem 1989;264(35);21239-46. PMID: 2687276

Alenin92: Alenin VV, Ostanin KV, Kostikova TR, Domkin VD, Zubova VA, Smirnov MN (1992). "[Substrate specificity of phosphoribosyl-aminoimidazole-succinocarboxamide synthetase (SAICAR-synthetase) from Saccharomyces cerevisiae yeast]." Biokhimiia 1992;57(6);845-55. PMID: 1420588

Allard92: Allard P, Kuprin S, Shen B, Ehrenberg A (1992). "Binding of the competitive inhibitor dCDP to ribonucleoside-diphosphate reductase from Escherichia coli studied by 1H NMR. Different properties of the large protein subunit and the holoenzyme." Eur J Biochem 1992;208(3);635-42. PMID: 1396671

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

Anand04: Anand R, Hoskins AA, Stubbe J, Ealick SE (2004). "Domain organization of Salmonella typhimurium formylglycinamide ribonucleotide amidotransferase revealed by X-ray crystallography." Biochemistry 43(32);10328-42. PMID: 15301531

Andersson99: Andersson ME, Hogbom M, Rinaldo-Matthis A, Andersson KK, Sjoberg BM, Nordlund P (1999). "The Crystal Structure of an Azide Complex of the Diferrous R2 Subunit of Ribonucleotide Reductase Displays a Novel Carboxylate Shift with Important Mechanistic Implications for Diiron-Catalyzed Oxygen Activation." J. Am. Chem. Soc. 121: 2346-2352.

Andrews11: Andrews SC (2011). "Making DNA without iron - induction of a manganese-dependent ribonucleotide reductase in response to iron starvation." Mol Microbiol 80(2);286-9. PMID: 21371140

Artin09: Artin E, Wang J, Lohman GJ, Yokoyama K, Yu G, Griffin RG, Bar G, Stubbe J (2009). "Insight into the mechanism of inactivation of ribonucleotide reductase by gemcitabine 5'-diphosphate in the presence or absence of reductant." Biochemistry 48(49);11622-9. PMID: 19899770

Assarsson01: Assarsson M, Andersson ME, Hogbom M, Persson BO, Sahlin M, Barra AL, Sjoberg BM, Nordlund P, Graslund A (2001). "Restoring proper radical generation by azide binding to the iron site of the E238A mutant R2 protein of ribonucleotide reductase from Escherichia coli." J Biol Chem 276(29);26852-9. PMID: 11328804

Axelrod08: Axelrod HL, McMullan D, Krishna SS, Miller MD, Elsliger MA, Abdubek P, Ambing E, Astakhova T, Carlton D, Chiu HJ, Clayton T, Duan L, Feuerhelm J, Grzechnik SK, Hale J, Han GW, Haugen J, Jaroszewski L, Jin KK, Klock HE, Knuth MW, Koesema E, Morse AT, Nigoghossian E, Okach L, Oommachen S, Paulsen J, Quijano K, Reyes R, Rife CL, van den Bedem H, Weekes D, White A, Wolf G, Xu Q, Hodgson KO, Wooley J, Deacon AM, Godzik A, Lesley SA, Wilson IA (2008). "Crystal structure of AICAR transformylase IMP cyclohydrolase (TM1249) from Thermotoga maritima at 1.88 A resolution." Proteins 71(2);1042-9. PMID: 18260100

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

Barnes94: Barnes TS, Bleskan JH, Hart IM, Walton KA, Barton JW, Patterson D (1994). "Purification of, generation of monoclonal antibodies to, and mapping of phosphoribosyl N-formylglycinamide amidotransferase." Biochemistry 33(7);1850-60. PMID: 8110788

Barzu83: Barzu O, Michelson S (1983). "Simple and fast purification of Escherichia coli adenylate kinase." FEBS Lett 1983;153(2);280-4. PMID: 6311616

Bass87: Bass MB, Fromm HJ, Stayton MM (1987). "Overproduction, purification, and characterization of adenylosuccinate synthetase from Escherichia coli." Arch Biochem Biophys 1987;256(1);335-42. PMID: 3038024

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

Bera00: Bera AK, Smith JL, Zalkin H (2000). "Dual role for the glutamine phosphoribosylpyrophosphate amidotransferase ammonia channel. Interdomain signaling and intermediate channeling." J Biol Chem 275(11);7975-9. PMID: 10713115

Bera99: Bera AK, Chen S, Smith JL, Zalkin H (1999). "Interdomain signaling in glutamine phosphoribosylpyrophosphate amidotransferase." J Biol Chem 274(51);36498-504. PMID: 10593947

Berardi99: Berardi MJ, Bushweller JH (1999). "Binding specificity and mechanistic insight into glutaredoxin-catalyzed protein disulfide reduction." J Mol Biol 292(1);151-61. PMID: 10493864

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

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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 SRI International Pathway Tools version 18.5 on Sun Mar 1, 2015, biocyc13.