Metabolic Modeling Tutorial
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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014

Caulobacter crescentus CB15 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.

Locations of Mapped Genes:

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 [White97a]. Some organisms, such as the mycoplasmas, do not biosynthesize purine and pyrimidine bases de novo and must rely on salvage pathways [Wang01f].

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.

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

Created in MetaCyc 17-Dec-2002 by Arnaud M , SRI International
Imported from MetaCyc 18-Sep-2013 by Fulcher CA , 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

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

Wang01f: 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

White97a: 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

Dyson90: Dyson HJ, Gippert GP, Case DA, Holmgren A, Wright PE (1990). "Three-dimensional solution structure of the reduced form of Escherichia coli thioredoxin determined by nuclear magnetic resonance spectroscopy." Biochemistry 1990;29(17);4129-36. PMID: 2193685

Eklund84: Eklund H, Cambillau C, Sjoberg BM, Holmgren A, Jornvall H, Hoog JO, Branden CI (1984). "Conformational and functional similarities between glutaredoxin and thioredoxins." EMBO J 1984;3(7);1443-9. PMID: 6378624

Gleason88: Gleason FK, Holmgren A (1988). "Thioredoxin and related proteins in procaryotes." FEMS Microbiol Rev 1988;4(4);271-97. PMID: 3152490

Gleason90: Gleason FK, Lim CJ, Gerami-Nejad M, Fuchs JA (1990). "Characterization of Escherichia coli thioredoxins with altered active site residues." Biochemistry 1990;29(15);3701-9. PMID: 2187529

Green04: Green ML, Karp PD (2004). "A Bayesian method for identifying missing enzymes in predicted metabolic pathway databases." BMC Bioinformatics 5;76. PMID: 15189570

Holmgren85: Holmgren A (1985). "Thioredoxin." Annu Rev Biochem 1985;54;237-71. PMID: 3896121

Katti90: Katti SK, LeMaster DM, Eklund H (1990). "Crystal structure of thioredoxin from Escherichia coli at 1.68 A resolution." J Mol Biol 1990;212(1);167-84. PMID: 2181145

Mueller94: Mueller EJ, Meyer E, Rudolph J, Davisson VJ, Stubbe J (1994). "N5-carboxyaminoimidazole ribonucleotide: evidence for a new intermediate and two new enzymatic activities in the de novo purine biosynthetic pathway of Escherichia coli." Biochemistry 33(8);2269-78. PMID: 8117684

Nikkola93: Nikkola M, Gleason FK, Fuchs JA, Eklund H (1993). "Crystal structure analysis of a mutant Escherichia coli thioredoxin in which lysine 36 is replaced by glutamic acid." Biochemistry 1993;32(19);5093-8. PMID: 8098620

Setif01: Setif P (2001). "Ferredoxin and flavodoxin reduction by photosystem I." Biochim Biophys Acta 1507(1-3);161-79. PMID: 11687213

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