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

IMPDH1 and IMPDH2 are closely related, NAD⁺-dependent oxidoreductase enzymes essential for de novo guanine nucleotide synthesis by converting inosine monophosphate (IMP) to xanthosine monophosphate (XMP)[4][1]. While both catalyze the same reaction, they have distinct tissue distributions and regulatory mechanisms: **IMPDH1** is especially prominent in the retina (where it is crucial for photoreceptor cGMP signaling and mutations cause inherited retinal degeneration), while **IMPDH2** is abundant in proliferating cells and the central nervous system, with mutations linked to neurodevelopmental disorders[3][6][7][8]. Both are important therapeutic targets—**IMPDH inhibitors** such as mycophenolic acid and ribavirin have immunosuppressive and antiviral actions by depleting guanine nucleotides, making these enzymes relevant in transplant medicine, oncology, and infectious disease[5][9]. Structural differences, especially in regulatory responses and filament assembly, contribute to tissue-specific regulation[1][2].

Other names

IMP dehydrogenase 1IMP dehydrogenase 2IMPDHIIMPDHII

Competitive inhibition of the active site, blocking IMP oxidation to XMP and depleting intracellular guanine nucleotides\nSuppression of downstream DNA/RNA synthesis, leading to antiproliferative, immunosuppressive, or antiviral effects