Design, synthesis and antiviral evaluation of purine-β-lactam and purine-aminopropanol hybrids.


In animal cells amido phosphoribosyltransferase or PRPP amidotransferase (ATase or PRAT; EC catalyzes the first step in de novo purine synthesis and is sensitive to feedback regulation by purine ribonucleotides produced by the salvage cycle. Inhibition of ATase in cultured fibroblasts regulates not only purine de novo synthesis but also the rates of DNA and protein synthesis and cell growth (). While it is known that plant ATase is sensitive to feedback regulation () the impact of this inhibition on plant cellular metabolism has not been examined thoroughly. Isolation of cDNAs derived from two Arabidopsis ATase genes (Genbank accessions D28868 and D28869) of similar sequence by should be helpful in clarifying the activity and regulation of this enzyme. The two ATase sequences, designated AtATase1 and 2, were recovered in a screen for sequences preferentially transcribed in young floral buds. Whereas AtATase1 transcript levels are highest in flowers and roots and absent in leaves, AtATase2 transcripts are most abundant in leaves, only moderately expressed in flowers and very weakly accumulated in roots. The predicted amino acid sequences of these genes are most similar to the [4Fe-4S] cluster-dependent group of ATases that are activated by cleavage of a propeptide ( and references therein). Since the Arabidopsis sequences contain the conserved residues for the propeptide cleavage site it is likely, but unproven, that the plant enzyme is activated similarly. The putative propeptides of the Arabidopsis sequences are particularly long and so may also contain additional functions such as a signal for targeting to the chloroplast (). reported cloning an Arabidopsis ATase gene that they designated PUR1 since its product catalyzes the first step in de novo purine synthesis. However, the relationship of PUR1 to the genes described by has not been described. PUR1 transcripts are found in all organs with the highest levels accumulating in flowers, leaves and stems ().

“Design, Synthesis and Antiviral Evaluation of Purine-β-lactam and Purine-aminopropanol Hybrids.”  55 (11): 5637–5641.

Purine and Pyrimidines : Structure, Synthesis and Metabolism

All nucleotides contain a ribose sugar and phosphate that form the backbone of DNA and RNA. These are synthesized from ribose 5-phosphate, a central metabolite of the pentose phosphate pathway. In this single step reaction, two of the phosphates of ATP are transferred to ribose 5-phosphate to form 5-phospho--D-ribosyl 1-pyrophosphate (PRPP). This intermediate is required for the biosynthesis of purines, pyrimidines, NAD, histidine and tryptophan. It plays a critical role in anabolism.

Here we review the biochemical properties and genes of each enzyme involved in the pyrimidine nucleotide biosynthesis de novo.

Citation: Moffatt B.A., and Ashihara H. (2002) Purine and Pyrimidine Nucleotide Synthesis and Metabolism. The Arabidopsis Book 1:e0018. doi:10.1199/tab.0018

deaminase in order to feed the cytosolic branch of the purine synthesis ..

De Novo Purine Synthesis Flashcards | Quizlet

Purine and pyrimidine nucleotides are major energy carriers, subunits of nucleic acids and precursors for the synthesis of nucleotide cofactors such as NAD and SAM. Despite the obvious importance of these molecules, we still have much to learn about how these nucleotides are synthesized and metabolized by plants. Moreover, of the research that has been done in this area relatively little has used genetic analysis to evaluate the function(s) of specific enzymes.

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The pathways for the synthesis of nucleotides in plant cells are similar to those found in animals and microorganisms. This conclusion is based primarily on the results of studies using in vivo radiotracers, specific inhibitors of nucleotide synthesis and on analyses of the kinetic parameters of purified enzymes involved in nucleotide synthesis that are unlikely to have similar demands for purine and pyrimidine nucleotides have been used in this research. A more comprehensive understanding of the role(s) of specific nucleotide biosynthetic enzymes throughout plant development and factors that regulate their activity/expression is still lacking. Ultimately this information will explain how the requirements of different plants are met, such as those of ureide-producing legumes () or those synthesizing caffeine (; ).

Excessive drive of de novo purine synthesis ..

Inhibitors of purine and pyrimidine synthesis mycophenolate, azathioprine, and leflunomide. These drugs act by inhibiting cell division and inducing cell death. Oct 10, 2017. dADP and dATP negatively feedback and inhibit enzyme. purine. pathway diagram. insufficient capacity in most cells; important enzymes.

Pyrimidine (U & C) Biosynthesis - YouTube

There are two principal routes for the synthesis of nucleotides: the de novo and the salvage pathways ( and , and , respectively). Using 5-phosphoribosyl-1-pyrophosphate (PRPP), the de novo pathway enzymes build purine and pyrimidine nucleotides from “scratch” using simple molecules such as CO2, amino acids and tetrahydrofolate. This route of nucleotide synthesis has a high requirement for energy as compared that of the salvage pathway. For example, five of the 12 steps of de novo purine synthesis require hydrolysis of ATP or GTP but only one salvage cycle reaction uses ATP. The enzymes of both of these biosynthetic routes are classified as “housekeeping” enzymes because they perform basic, cellular activities and are assumed to be present in low, constitutive levels in all cells. Whereas the de novo pathway is thought to reside in plastids, salvage cycle enzymes may be localized in more than one compartment.