Inositol monophosphatase (E.C. 3.1.3.25, IMPase, myo-inositol-1(or 4)-phosphate phosphohydrolase) is a magnesium-dependent homodimer which hydrolyses myo-inositol monophosphate to generate myo-inositol and phosphate. Glycerol may be a physiological phosphate acceptor. Li⁺ is a nonselective un-competitive inhibitor more potent at IMPase 1 (pK_i ca. 3.5, [3]; pIC₅₀ 3.2, [4]) than IMPase 2 (pIC₅₀ 1.8-2.1, [4]). IMPase activity may be inhibited competitively by L690330 (pK_i 5.5, [3]), although the enzyme selectivity is not yet established.

Polymorphisms in either of the genes encoding these enzymes have been linked with bipolar disorder [5-7]. Disruption of the gene encoding IMPase 1, but not IMPase 2, appears to mimic the effects of Li⁺ in mice [1-2].

1. Cryns K, Shamir A, Shapiro J, Daneels G, Goris I, Van Craenendonck H, Straetemans R, Belmaker RH, Agam G, Moechars D et al.. (2007) Lack of lithium-like behavioral and molecular effects in IMPA2 knockout mice. Neuropsychopharmacology, 32 (4): 881-91. [PMID:16841073]

2. Cryns K, Shamir A, Van Acker N, Levi I, Daneels G, Goris I, Bouwknecht JA, Andries L, Kass S, Agam G et al.. (2008) IMPA1 is essential for embryonic development and lithium-like pilocarpine sensitivity. Neuropsychopharmacology, 33 (3): 674-84. [PMID:17460611]

3. McAllister G, Whiting P, Hammond EA, Knowles MR, Atack JR, Bailey FJ, Maigetter R, Ragan CI. (1992) cDNA cloning of human and rat brain myo-inositol monophosphatase. Expression and characterization of the human recombinant enzyme. Biochem. J., 284 ( Pt 3): 749-54. [PMID:1377913]

4. Ohnishi T, Ohba H, Seo KC, Im J, Sato Y, Iwayama Y, Furuichi T, Chung SK, Yoshikawa T. (2007) Spatial expression patterns and biochemical properties distinguish a second myo-inositol monophosphatase IMPA2 from IMPA1. J. Biol. Chem., 282 (1): 637-46. [PMID:17068342]

5. Sjøholt G, Gulbrandsen AK, Løvlie R, Berle JO, Molven A, Steen VM. (2000) A human myo-inositol monophosphatase gene (IMPA2) localized in a putative susceptibility region for bipolar disorder on chromosome 18p11.2: genomic structure and polymorphism screening in manic-depressive patients. Mol. Psychiatry, 5 (2): 172-80. [PMID:10822345]

6. Sjøholt G, Molven A, Løvlie R, Wilcox A, Sikela JM, Steen VM. (1997) Genomic structure and chromosomal localization of a human myo-inositol monophosphatase gene (IMPA). Genomics, 45 (1): 113-22. [PMID:9339367]

7. Yoshikawa T, Turner G, Esterling LE, Sanders AR, Detera-Wadleigh SD. (1997) A novel human myo-inositol monophosphatase gene, IMP.18p, maps to a susceptibility region for bipolar disorder. Mol. Psychiatry, 2 (5): 393-7. [PMID:9322233]