Overview: Inositol monophosphatase (IMPase, myo-inositol-1(or 4)-phosphate phosphohydrolase) is a magnesium-dependent homodimer that hydrolyses myo-inositol monophosphate to generate myo-inositol and phosphate. Glycerol may be a physiological phosphate acceptor. Lithium is a nonselective un-competitive inhibitor more potent at IMPase 1 (pKi ca 3.5, McAllister et al., 1992; pIC50 3.2, Ohnishi et al., 2007) than IMPase 2 (pIC50 1.8–2.1, Ohnishi et al., 2007). IMPase activity may be inhibited competitively by L690330 (pKi 5.5, McAllister et al., 1992), although the enzyme selectivity is not yet established.
| Nomenclature | IMPase 1 | IMPase 2 |
|---|---|---|
| Other names | IMPA1 | IMPA2 |
| Ensembl ID | ENSG00000133731 | ENSG00000141401 |
| Rank order of affinity | Inositol 4-phosphate > inositol 3-phosphate > inositol 1-phosphate (McAllister et al., 1992) | – |
Polymorphisms in either of the genes encoding these enzymes have been linked with bipolar disorder (Sjoholt et al., 1997; Yoshikawa et al., 1997; Sjoholt et al., 2000). Disruption of the gene encoding IMPase 1, but not IMPase 2, appears to mimic the effects of lithium in mice (Cryns et al., 2007; 2008;).
Glossary
Abbreviations:
- L690330
1-(4-hydroxyphenoxy)ethane-1,1-bisphosphonate
Further Reading
Ikeda A, Kato T (2003). Biological predictors of lithium response in bipolar disorder. Psychiatry Clin Neurosci57: 243–250.
Lenox RH, Wang L (2003). Molecular basis of lithium action: integration of lithium-responsive signaling and gene expression networks. Mol Psychiatry8: 135–144.
Miller DJ, Allemann RK (2007). myo-Inositol monophosphatase: a challenging target for mood stabilising drugs. Mini Rev Med Chem7: 107–113.
References
- Cryns K, et al. Neuropsychopharmacology. 2007;32:881–891. doi: 10.1038/sj.npp.1301154. [DOI] [PubMed] [Google Scholar]
- Cryns K, et al. Neuropsychopharmacology. 2008;33:674–684. doi: 10.1038/sj.npp.1301431. [DOI] [PubMed] [Google Scholar]
- McAllister G, et al. Biochem J. 1992;284:749–754. doi: 10.1042/bj2840749. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ohnishi T, et al. J Biol Chem. 2007;282:637–646. doi: 10.1074/jbc.M604474200. [DOI] [PubMed] [Google Scholar]
- Sjoholt G, et al. Genomics. 1997;45:113–122. [Google Scholar]
- Sjoholt G, et al. Mol Psychiatry. 2000;5:172–180. doi: 10.1038/sj.mp.4000681. [DOI] [PubMed] [Google Scholar]
- Yoshikawa T, et al. Mol Psychiatry. 1997;2:393–397. doi: 10.1038/sj.mp.4000325. [DOI] [PubMed] [Google Scholar]