Inosine-5′-monophosphate dehydrogenase (IMPDH)

Inosine‑5′‑monophosphate dehydrogenase (IMPDH) is a key enzyme that catalyzes the NAD⁺-dependent oxidation of inosine monophosphate (IMP) to xanthosine monophosphate (XMP), representing the first committed and rate-limiting step in the *de novo* biosynthesis of guanine nucleotides from IMP. This reaction is essential for maintaining intracellular pools of GTP, which are required for DNA and RNA synthesis, signal transduction pathways, energy transfer processes, glycoprotein production, and overall cellular proliferation. The enzyme exists as a tetramer or octamer with each subunit containing a catalytic TIM barrel domain and a regulatory Bateman domain composed of cystathionine beta-synthase repeats. There are two main human isoforms—IMPDH1 with housekeeping roles and IMPDH2 upregulated in proliferative diseases such as leukemia. Because it is crucial for cell growth and division, especially in immune cells or rapidly dividing cancer cells, IMPDH is an established therapeutic target for immunosuppressive agents like mycophenolic acid as well as antiviral and antimicrobial drugs. Selectivity between bacterial/mammalian enzymes enables its use against infectious diseases; however, challenges remain regarding isoform specificity within humans due to high sequence similarity[1][2][3][4][5].

Other names

Inosinate dehydrogenaseIMP dehydrogenaseInosine monophosphate dehydrogenase

Competitive inhibition of the enzyme’s active site to block GMP biosynthesis, leading to depletion of guanine nucleotides and suppression of DNA/RNA synthesis in rapidly dividing cells or pathogens[1][5].