Reactome: A Curated Pathway Database

IMP + H2O + NAD+ => XMP + NADH + H+ [IMPDH1,2]

Stable Identifier
R-HSA-73794
Type
Reaction
Species
Homo sapiens
Compartment
Synonyms
inosine 5'-monophosphate (IMP) + NAD+ + H2O => xanthosine 5'-monophosphate (XMP) + NADH + H+
Locations in the PathwayBrowser
Summation

Two human isoenzymes, IMP dehydrogenase 1 and 2 (IMPDH1,2) catalyze the irreversible dehydrogenation of inosine 5'-monophosphate (IMP) to form xanthosine 5'-monophosphate (XMP). The active forms of both isoenzymes are homotetramers, and they are nearly identical in their catalytic efficiencies and their susceptibility to inhibition by XMP (Carr et al. 1993; Colby et al. 1999; Hager et al. 1995). Both enzymes occur as homotetramers (Colby et al. 1999 - IMPDH2; unpubliched data in PDB 1JCN IMPDH1). A variety of experiments suggest that IMPDH1 and 2 have distinct functions in vivo. While IMPDH1 is expressed at constant levels, IMPDH2 is expressed at elevated levels in tumor cells and in mitotic normal cells. In humans, heterozygosity for mutant forms of IMPDH1 is associated with a form of retinitis pigmentosa (Bowne et al. 2002). In laboratory mice, mutations that disrupt the homologue of IMPDH1 have no obvious effect at the level of the whole organism, while ones that disrupt IMPDH2 are lethal (Gu et al. 2003).

This reaction is the rate limiting step in the synthesis of guanosine 5'-monophosphate (GMP) from IMP, and GMP competitively inhibits the well-characterized bacterial IMP dehydrogenase enzyme. Evidence for an inhibitory effect of GMP on the human isoenzymes has not been reported. Rather, they appear to be inhibited by XMP; in addition, transcription of one or both IMP dehydrogenase mRNAs may be inhibited by high cellular GMP concentrations (Glesne et al. 1991).

Literature References
PubMed ID Title Journal Year
Participants
Participant Of
This entity is regulated by:
Title Physical Entity Activity
IMP dehydrogenase activity of IMPDH tetramers [cytosol] IMPDH tetramers [cytosol] IMP dehydrogenase activity (0003938)
Orthologous Events
Cross References
Rhea