Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1) (IMPDH1)

Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1) is a rate-limiting enzyme in the de novo synthesis of guanine nucleotides, catalyzing the NAD-dependent conversion of inosine monophosphate (IMP) to xanthosine monophosphate (XMP) [1.3.3, 1.3.5]. It plays a crucial role in maintaining intracellular guanine nucleotide pools, which are essential for DNA and RNA synthesis, signal transduction, and cell proliferation [1.2.4, 1.4.2]. While IMPDH1 is expressed at low levels in most tissues, it is highly expressed in the retina, spleen, and peripheral blood leukocytes [1.1.2, 1.3.5]. Mutations in the IMPDH1 gene are a primary cause of autosomal dominant retinitis pigmentosa (RP10) and Leber congenital amaurosis (LCA11), leading to progressive vision loss [1.1.3, 1.4.2]. Due to its central role in lymphocyte proliferation, IMPDH1 is a major therapeutic target for immunosuppressive drugs like mycophenolic acid, as well as antiviral and anticancer agents [1.2.3, 1.3.3]. The enzyme also exhibits moonlighting functions, including nucleic acid binding and potential roles in RNA/DNA metabolism [1.2.3, 1.4.1]. Inhibition of IMPDH1 leads to the depletion of GTP and GDP, which is particularly effective in suppressing the immune response by limiting T and B cell expansion [1.2.2, 1.3.5].

Other names

IMPDH-IIMPD1IMP dehydrogenase 1LCA11RP10sWSS2608hIMPDH1

Inhibition of the rate-limiting step in de novo guanine nucleotide biosynthesis by preventing the conversion of inosine-5'-monophosphate (IMP) to xanthosine-5'-monophosphate (XMP) [1.3.3, 1.3.5]. This leads to the depletion of intracellular GTP and GDP pools, which subsequently inhibits DNA synthesis and cell proliferation, particularly in T and B lymphocytes [1.2.2, 1.2.4].