Search results for IMPDH1

Showing 9 results out of 9

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Species

Types

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Protein (5 results from a total of 5)

Identifier: R-HSA-6800971
Species: Homo sapiens
Compartment: secretory granule lumen
Primary external reference: UniProt: IMPDH1: P20839
Identifier: R-HSA-6800927
Species: Homo sapiens
Compartment: ficolin-1-rich granule lumen
Primary external reference: UniProt: IMPDH1: P20839
Identifier: R-HSA-57348
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: IMPDH1: P20839
Identifier: R-HSA-6806182
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: P20839
Identifier: R-HSA-6799173
Species: Homo sapiens
Compartment: azurophil granule lumen
Primary external reference: UniProt: P20839

Interactor (1 results from a total of 1)

Identifier: P20839-3
Species: Homo sapiens
Primary external reference: UniProt: P20839-3

Complex (1 results from a total of 1)

Identifier: R-HSA-111583
Species: Homo sapiens
Compartment: cytosol

Reaction (2 results from a total of 2)

Identifier: R-HSA-73794
Species: Homo sapiens
Compartment: cytosol
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).

Identifier: R-HSA-9678749
Species: Homo sapiens
Compartment: cytosol
Inhibition of host inosine monophosphate dehydrogenases 1 and 2 (IMPDH1, IMPDH2) and subsequent depletion of cellular GTP pools is proposed to be a mechanism of action of IMPDH inhibitors (ribavirin, thioguanine, mycophenolic acid). IMPDH tetramers catalyzes the rate-limiting step where inosine 5′-monophosphate is converted to xanthine monophosphate during guanosine monophosphate (GMP) synthesis. GMP is later converted to guanosine triphosphate (GTP). IMPDH inhibitors mimic inosine 5′-monophosphate and act as competitive inhibitors of IMPDH (Nelson et al. 1990, Vethe et al. 2008, Elgemeie 2003, Te et al. 2007). Inhibited de novo synthesis of guanine nucleotides and decreased intracellular GTP pools leads to a decline in viral protein synthesis and limit replication of viral genomes (Mori et al. 2011).
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