Inosine-5'-monophosphate dehydrogenase type I (IMPDH1)

Inosine-5'-monophosphate dehydrogenase type I (IMPDH1) is a key rate-limiting enzyme in the de novo biosynthetic pathway of guanine nucleotides, catalyzing the nicotinamide adenine dinucleotide (NAD)-dependent oxidation of inosine-5'-monophosphate (IMP) to xanthosine-5'-monophosphate (XMP) [1, 10]. It is one of two isoforms in humans, with IMPDH1 being constitutively expressed at low levels in most tissues but showing particularly high expression in the retina and spleen [1, 14]. Mutations in the IMPDH1 gene are a primary cause of hereditary retinal dystrophies, specifically retinitis pigmentosa type 10 (RP10) and Leber congenital amaurosis type 11 (LCA11), likely due to the high demand for GTP in the phototransduction cascade [1, 4, 16]. Beyond its role in vision, IMPDH1 is a significant therapeutic target for immunosuppressive, antiviral, and anticancer agents, as its inhibition depletes the intracellular GTP and dGTP pools required for the proliferation of T and B lymphocytes and malignant cells [10, 13]. Drugs such as mycophenolic acid and ribavirin exert their effects by binding to the enzyme and preventing the production of guanosine monophosphate (GMP) [4, 12]. Recent research also highlights IMPDH1 as a potential prognostic biomarker in various cancers, such as hepatocellular carcinoma and colorectal cancer, where its upregulation correlates with poor clinical outcomes and tumor progression [17, 20].

Other names

IMPD1IMPDH-IIMPDH 1Inosine monophosphate dehydrogenase 1RP10LCA11sWSS2608

Inhibition of the conversion of inosine-5'-monophosphate (IMP) to xanthosine-5'-monophosphate (XMP), the rate-limiting step in de novo guanine nucleotide biosynthesis, leading to depletion of intracellular GTP and dGTP pools.