Bacteria have a salvage pathway for the pyrimidine bases.

Phosphoribosyltransferases allow PRPP to be added to purine bases to generate nucleotides () and are required for a functional, purine salvage pathway. H. pylori has two known phosphoribosyltransferases, HP0735 and HP0572, currently believed to encode guanine-phosphoribosyltransferase (Gpt) and adenine-phosphoribosyltransferase (Apt), respectively (, ). We were successful in completely deleting the H. pylori apt gene, and interestingly, defined medium growth assays in RnP medium showed a reduced ability of this mutant to utilize guanine or guanosine (and to a lesser extent, xanthine) for growth, while only marginal growth abnormalities were seen when the mutant when grown on adenine (A). This indicates that in H. pylori strain G27, Apt uses guanine as its primary substrate and that the conversion of adenine directly to ATP via Apt potentially is not the major mechanism for ATP generation when H. pylori is grown on adenine. When a copy of apt was inserted into the rdxA locus of the Δapt mutant strain, the ability to grow on guanine was restored (B).

Salvage and Biosynthetic Pathways

Biosynthesis of the pyrimidine ring. Precursors of the ring and numbering of the ring atoms.

Nucleotide Synthesis via Salvage Pathway

A second form of gout results from partial or complete deficiency of a purine salvage enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This enzyme catalyzes the following reactions:

Purine & Pyrimidine Synthesis (de-novo) | easybiologyclass

It is not yet clear why this deficiency accelerates purine synthesis. One model states that in the absence of these salvage pathways, GMP levels decline which, in turn, modulates the feedback inhibition of PRPP amidotransferase by this nucleotide. Alternatively, it has been proposed that decreased flux through this salvage pathway causes PRPP to accumulate and this, in turn, accelerates flux through PRPP amidotransferase by substrate level control.

Figure 4. Pathways of purine nucleotide catabolism to uric acid. R-1-P is ribose 1-phosphate.
Most intracellular purine bases are salvaged and pyrimidine salvage probably occurs.

Purine Salvage Pathway - NEET PG TEST SERIES

Disruption of the purine nucleotide metabolismgenerally results in an accumulation and/or a lack ofribonucleotides or deoxyribonucleotides or metabolic intermediateswith potentially cytotoxic consequences. The observed decreasedexpression of the 3 purine metabolism enzymes affects both synthesis and the salvage pathway of purine metabolism andmay also affect purine nucleotide homeostasis in TRAIL-resistantHBL-2/R cells. Such an imbalance may represent a selectivedisadvantage for the affected cells. Such a ‘weakness’ may not beapparent under normal circumstances but may become critical understress or unfavorable conditions. As the proliferation rates ofHBL-2/R and HBL-2 cells are comparable, the proposed imbalance inpurine nucleotide metabolism in TRAIL-resistant cells is possiblymild and/or well compensated . However, this‘weakness’ may become apparent due to lack of building blocks forDNA and RNA synthesis in the environment or upon further disruptionof purine metabolism. Since both pathways of purine metabolism arecompromised in TRAIL-resistant MCL cells, these cells should bevulnerable to further inactivation of purine nucleotide metabolismenzymes. Therefore, drugs that target (already disbalanced) purinemetabolism should be highly cytotoxic to TRAIL-resistant cells(compared to non-malignant cells) and may therefore be selectivelyeffective in the elimination of TRAIL-resistant MCL cells inexperimental therapy. There are several approved inhibitors ofpurine metabolism, such as methotrexate (inhibits purine synthesis via dihydrofolate reductase) (), ribavirin and mycophenolic acid(inhibitors of IMPDH2) (,) or forodesine (a novel inhibitor ofPNP) (,), available for clinical use.

Zalkin H and Dixon JE (1992) De novo purine nucleotide synthesis. Progress in Nucleic Acid Research and Molecular Biology 42: 259–287.

activity which is required for de novo purine biosynthesis

As noted, a partial HGPRT deficiency leads to gout. A total deficiency of this enzyme has far more serious consequences. Lesch-Nyhan syndrome (8) involves not only severe hypericemia and gout but, in addition, the nervous system develops abnormally, leading to spasticity and behavioral problems, including aggressive behavior toward others and self-mutilation. Because the gene for HGPRT lies on the X-chromosome, the Lesch-Nyhan syndrome is sex-linked, having been observed only in males. Although the gouty arthritis of Lesch-Nyhan syndrome usually responds well to allopurinol, there is no known cure for the developmental and neurological abnormalities, and afflicted individuals rarely live beyond age 20. Moreover, although it is clear that all symptoms of this condition arise from the HGPRT deficiency, the specific relationship between the enzyme deficiency and the neuropathology is not understood.

Traut TW (1994) Physiological concentrations of purines and pyrimidines. Molecular and Cellular Biochemistry 140: 1–22.

Purine salvage pathway - Oxford Reference

Control of purine nucleotide synthesis involves both allosteric and genetic regulation. In most cells, PRPP synthetase, which synthesizes the first intermediate in IMP synthesis, is inhibited by AMP, ADP, and GDP, whereas PRPP amidotransferase (reaction 1), the primary control point for the overall reaction (2), is inhibited allosterically by AMP, ADP, GMP, and GDP. In E. coli, biosynthesis of the enzymes of IMP synthesis is inhibited by a repressor encoded by the purR gene. This protein binds either hypoxanthine or guanine, and the resultant protein-purine base complex binds to DNA sites upstream from promoters for several purine (and pyrimidine) biosynthetic enzymes. The crystal structure of the PurR repressor (3) shows it to be closely related to the well-known Lac repressor, which controls the lactose utilization operon by similar mechanisms.