Inosine monophosphate dehydrogenase (IMPDH) (IMPDH)

Inosine monophosphate dehydrogenase (IMPDH) is a key rate-limiting enzyme in the de novo pathway of guanine nucleotide biosynthesis, catalyzing the NAD+-dependent oxidation of inosine monophosphate (IMP) to xanthosine monophosphate (XMP) [1, 2]. It exists as two isoforms, IMPDH1 and IMPDH2; while IMPDH1 is constitutively expressed, IMPDH2 is significantly upregulated in proliferating cells, particularly T and B lymphocytes [3, 4]. Because lymphocytes lack significant purine salvage pathways, they are uniquely dependent on IMPDH for the production of GTP required for DNA synthesis and cellular signaling [4, 5]. Mycophenolic acid (MPA) acts as a potent, reversible, and non-competitive inhibitor of IMPDH, effectively depleting the intracellular guanosine nucleotide pool [5, 6]. This depletion leads to cell cycle arrest in the S phase, thereby suppressing lymphocyte proliferation and the subsequent immune response [1, 6]. Consequently, IMPDH is a primary therapeutic target for preventing organ transplant rejection and treating autoimmune disorders, and it is also being explored for its potential in antiviral and anticancer applications [2, 3].

Other names

IMP dehydrogenaseInosine-5'-monophosphate dehydrogenaseIMPDH1IMPDH2

Reversible, non-competitive inhibition of the enzyme, which blocks the conversion of inosine monophosphate (IMP) to xanthosine monophosphate (XMP), leading to the depletion of intracellular guanosine nucleotide pools and subsequent inhibition of DNA synthesis.