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|
Expected Taxonomic Range:
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
Unification Links: EcoCyc:DENOVOPURINE2-PWY
Martha Arnaud on Tue Jan 21, 2003:
This pathway supersedes the pathway formerly called "purine biosynthesis."
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