Inosine-5'-monophosphate dehydrogenase type 2 (IMPDH2)

Inosine-5'-monophosphate dehydrogenase type 2 (IMPDH2) is a pivotal enzyme that catalyzes the rate-limiting step in the de novo biosynthesis of guanine nucleotides (UniProt). It facilitates the NAD-dependent oxidation of inosine-5'-monophosphate (IMP) to xanthosine-5'-monophosphate (XMP), which is subsequently converted to GMP, GTP, and dGTP (NIH). While its isoform IMPDH1 is constitutively expressed in most tissues, IMPDH2 is significantly upregulated in rapidly proliferating cells, such as activated lymphocytes and various cancer cells (PubMed). This differential expression makes IMPDH2 a primary therapeutic target for immunosuppressive drugs like mycophenolate mofetil, which are used to prevent organ transplant rejection and treat autoimmune disorders (NIH). In oncology, IMPDH2 inhibition is explored to deplete the nucleotide pools necessary for DNA replication and RNA transcription, thereby inducing cell cycle arrest and apoptosis in tumors (PubMed). Beyond its catalytic function, IMPDH2 is involved in regulating cell signaling pathways and can form macromolecular structures known as "rods and rings" under metabolic stress (Wikipedia). Its expression levels often serve as a prognostic biomarker in cancers, correlating with increased malignancy and poor patient outcomes (NIH).

Other names

IMPDH-IIIMPD2IMP dehydrogenase 2Inosine-5'-monophosphate dehydrogenase 2Inosine-5'-monophosphate dehydrogenase type II

Inhibition of de novo guanine nucleotide biosynthesis by blocking the conversion of IMP to XMP, leading to depletion of intracellular GTP and dGTP pools (UniProt).