Synthesis of Purine Ribonucleotides

Nygaard P (1983) Utilization of preformed purine bases and nucleosides. In: Munch‐Petersen A (ed.) Metabolism in Nucleotides, Nucleosides and Nucleobases in Microorganisms, pp. 27–93. London: Academic Press.

Synthesis of Pyrimidine Ribonucleotides


Biosynthesis of Purine Nucleotides, Pyrimidine …

Zrenner R, Stitt M, Sonnewald U and Boldt R (2006) Pyrimidine and purine biosynthesis and degradation in plants. Annual Reviews of Plant Biology 57: 805–836.

Purine Nucleotide | Nucleotides | Biosynthesis - Scribd

Simmonds HA and van Gennip AH (2003) Purine and pyrimidine disorders. In: Blau N, Duran M, Blaskovics M and Gibson KM (eds) Physician's Guide to the Laboratory Diagnosis of Metabolic Diseases, pp. 445–465. Berlin: Springer.

This process has beentermed the purine nucleotide cycle (see diagram below).

The Synthesis and Degradation of Nucleotides

FIGURE 16–4 (a) De novo synthesis of pyrimidine nucleotides: biosynthesisof UTP and CTP via orotidylate. The pyrimidine is constructed from carbamoylphosphate and aspartate. The ribose 5-phosphate is then added to the completedpyrimidine ring by orotate phosphoribosyltransferase. The first step in thispathway (not shown here; is the synthesis of carbamoyl phosphate from CO2and NH4+, catalyzed in eukaryotes by carbamoyl phosphate synthetase II. (b)Channeling of intermediates in bacterial carbamoyl phosphate synthetase.(Derived from PDB ID 1M6V.) The large and small subunits are shown in gray andblue, respectively; the channel between active sites (almost 100 Å long) isshown as a yellow mesh. A glutamine molecule (green) binds to the small subunit,donating its amido nitrogen as NH4+ in a glutamine amidotransferase–typereaction. The NH4+ enters the channel, which takes it to a second active site,where it combines with bicarbonate in a reaction requiring ATP (bound ADP inblue). The carbamate then reenters the channel to reach the third active site,where it is phosphorylated to carbamoyl phosphate (bound ADP in red).

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a De Novo Nucleotide Biosynthesis Purine

Carbamoyl phosphate utilizedin pyrimidine nucleotide synthesis differs from that synthesized in the ureacycle; it is synthesized from glutamine instead of ammonia and is synthesizedin the cytosol.

As is true with purine nucleotides, the sugar phosphate portion ofthe molecule is supplied by PRPP.

Purine and pyrimidine nucleotide metabolism in Mollicutes

Stevens RC and Lipscomb WN (1992) A molecular mechanism for pyrimidine and purine nucleotide control of aspartate transcarbamylase. Proceedings of the National Academy of Sciences of the USA 89: 5281–5285.

OMP is thenconverted sequentially - not in a branched pathway - to the other pyrimidinenucleotides.


Three major feedback mechanisms cooperate in regulating the overall rate ofde novo purine nucleotide synthesis and the relative rates of formation of thetwo end products, adenylate and guanylate (Fig. 16–3). The first mechanism isexerted on the first reaction that is unique to purine synthesis—transfer of anamino group to PRPP to form 5-phosphoribosylamine. This reaction is catalyzed bythe allosteric enzyme glutamine-PRPP amidotransferase, which is inhibited by theend products IMP, AMP, and GMP. AMP and GMP act synergistically in thisconcerted inhibition. Thus, whenever either AMP or GMP accumulates to excess,the first step in its biosynthesis from PRPP is partially inhibited.
In the second control mechanism, exerted at a later stage, an excess of GMP inthe cell inhibits formation of xanthylate from inosinate by IMP dehydrogenase,without affecting the formation of AMP (Fig. 16–3). Conversely, an accumulationof adenylate inhibits formation of adenylosuccinate by adenylosuccinatesynthetase, without affecting the biosynthesis of GMP. In the third mechanism,GTP is required in the conversion of IMP to AMP (Fig. 16–2, step 1), whereas ATPis required for conversion of IMP to GMP (step 4), a reciprocal arrangement thattends to balance the synthesis of the two ribonucleotides.
The final control mechanism is the inhibition of PRPP synthesis by theallosteric regulation of ribose phosphate pyrophosphokinase. This enzyme isinhibited by ADP and GDP, in addition to metabolites from other pathways ofwhich PRPP is a starting point.