Inosine monophosphate dehydrogenase (IMPDH) and amidophosphoribosyltransferase (ATase) (IMPDH and ATase)

This entry refers to two distinct enzymes, Inosine monophosphate dehydrogenase (IMPDH) and Amidophosphoribosyltransferase (ATase), which are central to the de novo purine biosynthetic pathway. IMPDH serves as the rate-limiting enzyme for guanine nucleotide synthesis, converting inosine monophosphate (IMP) to xanthosine monophosphate (XMP) (UniProt P12268, P20839). ATase catalyzes the first committed step of the purine pathway by converting 5-phosphoribosyl-1-pyrophosphate (PRPP) to 5-phosphoribosyl-1-amine (UniProt Q06203). These enzymes are vital for maintaining the nucleotide pools required for DNA and RNA synthesis, particularly in cells with high proliferative demands such as activated lymphocytes and tumor cells (Hedstrom, 2009, Chem Rev). Because of their role in cell growth, they are significant targets for immunosuppressive, anticancer, and antiviral therapies. Drugs like mycophenolate mofetil and ribavirin target IMPDH, while thiopurines like 6-mercaptopurine produce metabolites that inhibit both ATase and IMPDH (DrugBank DB00688, DB01030). Inhibition of these targets leads to cell cycle arrest and apoptosis due to the depletion of essential purine precursors.

Other names

IMP dehydrogenaseInosinate dehydrogenaseGlutamine phosphoribosylpyrophosphate amidotransferasePhosphoribosylpyrophosphate amidotransferaseGPATPPAT

Inhibition of de novo purine nucleotide synthesis, leading to the depletion of intracellular guanine and adenine nucleotide pools, which results in the suppression of DNA and RNA synthesis and subsequent inhibition of cell proliferation.