Inosine-5'-monophosphate dehydrogenase 1 and Inosine-5'-monophosphate dehydrogenase 2 (IMPDH1, IMPDH2)

Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1) and Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) are central enzymes in purine metabolism, each catalyzing the NAD-dependent conversion of inosine monophosphate (IMP) to xanthosine monophosphate (XMP), the first committed and rate-limiting step for guanine nucleotide production. They consist of a canonical catalytic domain and a regulatory Bateman domain, assemble into higher-order structures (tetramers and octamers), and are regulated via allosteric nucleotide binding. IMPDH1 dominates in the retina, with disease-linked splice variants that regulate GTP synthesis for photoreceptor function. IMPDH2 is generally upregulated in cancers and used as an immunosuppressive target, mediating immune and proliferative responses by controlling guanine nucleotide pools. Both isoforms are susceptible to pharmacological inhibition, notably by mycophenolic acid, tiazofurin, and ribavirin—agents that influence enzyme structure, inhibit activity, and disrupt nucleotide homeostasis, with important therapeutic and safety implications in oncology and transplant medicine.

Other names

IMP dehydrogenase 1, IMPDH type I, IMPDH IIMP dehydrogenase 2, IMPDH type II, IMPDH IIInosine monophosphate dehydrogenase 1Inosine monophosphate dehydrogenase 2

Competitive inhibition of catalytic activity by direct inhibition at the active site. Allosteric modulation impacting filament assembly and enzyme conformation (notably in IMPDH2). Depletion of guanine nucleotides, leading to decreased DNA/RNA synthesis, impacting cell proliferation and immune function.