Inosine-5'-monophosphate dehydrogenase (IMPDH) (IMPDH)

Inosine-5'-monophosphate dehydrogenase (IMPDH) is a pivotal rate-limiting enzyme in the de novo synthesis of guanosine nucleotides, catalyzing the nicotinamide adenine dinucleotide (NAD+)-dependent oxidation of inosine monophosphate (IMP) to xanthosine monophosphate (XMP) (Source: UniProt, P12268). This enzyme exists in two isoforms, IMPDH1 and IMPDH2, with the latter being significantly upregulated in proliferating cells, particularly activated T and B lymphocytes (Source: PubMed, PMID: 15588047). Because lymphocytes lack a robust salvage pathway for purine synthesis and rely almost exclusively on the de novo pathway, IMPDH serves as a highly selective target for immunosuppression. Drugs such as mycophenolic acid (MPA) act as potent, reversible, uncompetitive inhibitors of IMPDH, effectively halting the cell cycle in the S-phase and preventing lymphocyte proliferation (Source: StatPearls, NBK559031). Beyond its role in preventing organ transplant rejection and managing autoimmune conditions like lupus nephritis, IMPDH is also a target of interest in oncology and virology due to the high demand for guanine nucleotides in rapidly dividing cancer cells and viral replication (Source: PubMed, PMID: 29153129). The term "Mycophenolic acid exposure" refers to the pharmacokinetic measurement of the drug's presence in the body, which is critical for therapeutic drug monitoring to balance efficacy against risks like myelosuppression and gastrointestinal distress (Source: PubMed, PMID: 24595140).

Other names

IMP dehydrogenaseIMPD1IMPD2Inosine-5'-phosphate dehydrogenaseIMPDH1IMPDH2

Non-competitive, reversible inhibition of IMPDH, leading to the depletion of intracellular guanosine nucleotide pools (GMP, GDP, and GTP).