USMLE Step 1


Biochemical Pathways

De Novo Purine Synthesis

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De novo purine synthesis is a biochemical pathway that creates purine nucleotides from simple molecules. This can be contrasted against purine salvage, which recycles purines nucleotides after partial degradation.

De novo purine synthesis begins with the precursor molecule Ribose-5-phosphate (R5P) . R5P is then converted to its high energy, "activated" form, PRPP . This form enables the transfer of phosphoribosyl groups (such as R5P). This R5P transferred from PRPP forms the pentose sugar of the eventual purine nucleotide.

Next, PRPP undergoes a series of reactions that require aspartate , glycine , THF , and glutamine . Through these steps, PRPP is converted into 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 .

Finally, IMP can be converted to either AMP (adenosine monophosphate) or GMP (guanine monophosphate). The former reaction is especially important, as the drugs mycophenolate and ribavirin inhibit the enzyme IMP dehydrogenase, which converts IMP to GMP.

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