If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: purine biosynthesis 2
|Superclasses:||Biosynthesis → Nucleosides and Nucleotides Biosynthesis → Purine Nucleotide Biosynthesis → Purine Nucleotides De Novo Biosynthesis|
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 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
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
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
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
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
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
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
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
Bowne02: Bowne SJ, Sullivan LS, Blanton SH, Cepko CL, Blackshaw S, Birch DG, Hughbanks-Wheaton D, Heckenlively JR, Daiger SP (2002). "Mutations in the inosine monophosphate dehydrogenase 1 gene (IMPDH1) cause the RP10 form of autosomal dominant retinitis pigmentosa." Hum Mol Genet 11(5);559-68. PMID: 11875050
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