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MetaCyc Pathway: superpathway of purine nucleotides de novo biosynthesis I
Traceable author statement to experimental support

Pathway diagram: superpathway of purine nucleotides de novo biosynthesis I

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

Synonyms: purine biosynthesis 2

Superclasses: BiosynthesisNucleosides and Nucleotides BiosynthesisPurine Nucleotide BiosynthesisPurine Nucleotides De Novo Biosynthesis

Some taxa known to possess this pathway include : Arabidopsis thaliana col, Homo sapiens, Saccharomyces cerevisiae

Expected Taxonomic Range: Archaea, Bacteria , Eukaryota

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 [Wang01e].

In Saccharomyces cerevisiae regulation of the pathway occurs at both the enzyme level as shown in this pathway, and at the genetic level. For example, at the genetic level positive-acting regulatory proteins Bas1 and Pho2 and biosynthetic intermediates 5'-phosphoribosyl-4-(N-succinocarboxamide)-5-aminoimidazole and/or 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide are required to derepress ADE gene expression. Reviewed in [Rolfes06] and [Zalkin92].

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

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

Created 07-Jun-2001 by Pellegrini-Toole A, Marine Biological Laboratory
Revised 29-Oct-2007 by Fulcher CA, SRI International
Revised 15-Feb-2013 by Caspi R, SRI International


Rolfes06: Rolfes RJ (2006). "Regulation of purine nucleotide biosynthesis: in yeast and beyond." Biochem Soc Trans 34(Pt 5);786-90. PMID: 17052198

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

Wang01e: 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

Zalkin92: Zalkin H, Dixon JE (1992). "De novo purine nucleotide biosynthesis." Prog Nucleic Acid Res Mol Biol 42;259-87. PMID: 1574589

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

Abele95: Abele U, Schulz GE (1995). "High-resolution structures of adenylate kinase from yeast ligated with inhibitor Ap5A, showing the pathway of phosphoryl transfer." Protein Sci 4(7);1262-71. PMID: 7670369

Agarwal00: Agarwal AK, White PC (2000). "Structure of the VPATPD gene encoding subunit D of the human vacuolar proton ATPase." Biochem Biophys Res Commun 279(2);543-7. PMID: 11118322

Agarwal78: Agarwal KC, Miech RP, Parks RE (1978). "Guanylate kinases from human erythrocytes, hog brain, and rat liver." Methods Enzymol 51;483-90. PMID: 211390

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

alShawi92: al-Shawi MK, Senior AE (1992). "Catalytic sites of Escherichia coli F1-ATPase. Characterization of unisite catalysis at varied pH." Biochemistry 31(3);878-85. PMID: 1531027

Amutha03: Amutha B, Pain D (2003). "Nucleoside diphosphate kinase of Saccharomyces cerevisiae, Ynk1p: localization to the mitochondrial intermembrane space." Biochem J 370(Pt 3);805-15. PMID: 12472466

Andreichuk97: Andreichuk YuV , Domkin VD, Ryzhova TA, Koulikov VN, Kostikova TR (1997). "ADE6 gene of Saccharomyces cerevisiae yeast encoding formylglycinamidine-ribonucleotide synthetase. Cloning, sequencing, and analysis." Biochemistry (Mosc) 1997;62(7);742-52. PMID: 9331966

Bairoch93a: 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

Baud94: Baud V, Mears AJ, Lamour V, Scamps C, Duncan AM, McDermid HE, Lipinski M (1994). "The E subunit of vacuolar H(+)-ATPase localizes close to the centromere on human chromosome 22." Hum Mol Genet 3(2);335-9. PMID: 8004105

Beardsley89: Beardsley GP, Moroson BA, Taylor EC, Moran RG (1989). "A new folate antimetabolite, 5,10-dideaza-5,6,7,8-tetrahydrofolate is a potent inhibitor of de novo purine synthesis." J Biol Chem 264(1);328-33. PMID: 2909524

Bepler99: Bepler G, O'briant KC, Kim YC, Schreiber G, Pitterle DM (1999). "A 1.4-Mb high-resolution physical map and contig of chromosome segment 11p15.5 and genes in the LOH11A metastasis suppressor region." Genomics 55(2);164-75. PMID: 9933563

Berger80: Berger SJ, DeVries GW, Carter JG, Schulz DW, Passonneau PN, Lowry OH, Ferrendelli JA (1980). "The distribution of the components of the cyclic GMP cycle in retina." J Biol Chem 255(7);3128-33. PMID: 6102093

Bernasconi90: Bernasconi P, Rausch T, Struve I, Morgan L, Taiz L (1990). "An mRNA from human brain encodes an isoform of the B subunit of the vacuolar H(+)-ATPase." J Biol Chem 265(29);17428-31. PMID: 2145275

Beyenbach06: Beyenbach KW, Wieczorek H (2006). "The V-type H+ ATPase: molecular structure and function, physiological roles and regulation." J Exp Biol 209(Pt 4);577-89. PMID: 16449553

BlakePalmer07: Blake-Palmer KG, Su Y, Smith AN, Karet FE (2007). "Molecular cloning and characterization of a novel form of the human vacuolar H+-ATPase e-subunit: an essential proton pump component." Gene 393(1-2);94-100. PMID: 17350184

Blaszczyk01: Blaszczyk J, Li Y, Yan H, Ji X (2001). "Crystal structure of unligated guanylate kinase from yeast reveals GMP-induced conformational changes." J Mol Biol 307(1);247-57. PMID: 11243817

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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
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