Nucleotide Metabolism

Excerpt

There are only a few studies on the nucleotide metabolism of H. pylori, but together with the information derived from analyses of the genome of the bacterium, they have provided a wealth of information about the pathways of biosynthesis and degradation of pyrimidine and purine nucleotides, and showed that nucleotide biosynthetic enzymes are potential targets for antimicrobials designed against this organism.

H. pylori synthesizes pyrimidine nucleotides de novo and this pathway is essential for the growth and survival of the bacterium. This finding is in agreement with its limited capacity to salvage pyrimidines and the absence from its genome of key enzymes of pyrimidine salvage pathways. H. pylori can survive and proliferate by synthesizing de novo purine nucleotides, but it has yet to be established whether this pathway is essential for the bacterium. The organism incorporates preformed purines, and pathways for purine salvage are clearly identifiable in its genome. Although these salvage pathways act as energy-saving devices by utilizing the preformed purine ring and the ribose moiety of purine nucleosides, it has yet to be elucidated whether H. pylori can survive by having recourse only to purine salvage; and there is some evidence that these pathways may not be sufficient to support the integrity and proliferation of the bacterium.

Studies have demonstrated that targeting the inhibition of the de novo pyrimidine pathway presents valuable opportunities for the development of antimicrobial agents selective for H. pylori. The potential of the pathways of purine synthesis as therapeutic targets for antibacterials specific to H. pylori has yet to be explored, and to achieve this it is necessary to obtain a better understanding of the metabolism of purine nucleotides in the bacterium.