De Novo Purine Synthesis
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De novo purine synthesis refers to the biochemical pathway that creates purine nucleotides from simple molecules. This is in contrast to purine salvage, in which purines nucleotides are recycled after partial degradation. First, de novo purine synthesis starts with the precursor molecule R5P (ribose-5-phosphate). R5P is then converted to its high energy, "activated" form, PRPP. Since PRPP is high energy, it allows the transfer of phosphoribosyl groups (such as R5P). In de novo purine synthesis, it is this R5P from PRPP that forms the pentose sugar of the eventual purine nucleotide. Next, PRPP undergoes additional reactions that require aspartate, glycine, THF, glutamine, and others. It is these steps that convert PRPP to IMP (inosine monophosphate), the purine precursor molecule. The conversion of PRPP to IMP can be inhibited by the drug 6-MP (6-mercaptopurine) as well as by its prodrug azathioprine. Next, IMP can be converted to either AMP (adenosine monophosphate) or GMP (guanine monophosphate). The former reaction is especially important, as a couple drugs can be used at this step. The drugs mycophenolate and ribavirin inhibit the enzyme IMP dehydrogenase, which converts IMP to GMP.