InterPro domain: IPR001093

Synonym(s): Inosine-5'-monophosphate dehydrogenase, Inosinic acid dehydrogenase; Synonym(s): Guanosine 5'-monophosphate oxidoreductase

This entry contains two related enzymes: IMP dehydrogenase and GMP reductase. These enzymes adopt a TIM barrel structure.

IMP dehydrogenase ( 1.1.1.205 ) (IMPDH) catalyses the rate-limiting reaction of de novo GTP biosynthesis, the NAD-dependent reduction of IMP into XMP [ 1 ]. Inosine 5-phosphate + NAD ⁺ + H ₂ O = xanthosine 5-phosphate + NADH IMP dehydrogenase is associated with cell proliferation and is a possible target for cancer chemotherapy. Mammalian and bacterial IMPDHs are tetramers of identical chains. There are two IMP dehydrogenase isozymes in humans [ 2 ]. IMP dehydrogenase nearly always contains a long insertion that has two CBS domains within it.

GMP reductase ( 1.7.1.7 ) catalyses the irreversible and NADPH-dependent reductive deamination of GMP into IMP [ 3 ]. NADPH + guanosine 5-phosphate = NADP ⁺ + inosine 5-phosphate + NH ₃ It converts nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and maintains intracellular balance of A and G nucleotides.

1. Cloning and sequence analysis of the human and Chinese hamster inosine-5'-monophosphate dehydrogenase cDNAs. J. Biol. Chem. 263, 15769-72
2. Two distinct cDNAs for human IMP dehydrogenase. J. Biol. Chem. 265, 5292-5
3. Nucleotide sequence of the gene encoding the GMP reductase of Escherichia coli K12. Biochem. J. 255, 35-43