Inositol monophosphatase 1 explained

Inositol monophosphatase 1 is an enzyme that in humans is encoded by the IMPA1 gene.^{[1] [2]}

Interacting partners

IMPA1 has been shown to interact with Bergmann glial S100B^[3] and calbindin.^{[4] [5]}

Chemical inhibitors

L-690,330 is a competitive inhibitor of IMPase activity with very good activity in vitro however with limited bioavailability in vivo.^[6] Due to its increased specificity compared to Lithium, L-690,330 has been used extensively in characterizing the results of IMPase inhibition in various cell culture models. L-690,488, a prodrug or L-690,330, has also been developed which has greater cell permeability. Treatment of cortical slices with L-690,488 resulted in accumulation of inositol demonstrating the activity of this inhibitor in tissue.^[7]

Inhibition of IMPA1 activity can have pleiotropic effects on cellular function, including altering phosphoinositide signalling,^[8] autophagy, apoptosis,^[9] and other effects.

Bipolar disorder

Initially it was noticed that several drugs useful in treatment of bipolar disorder such as lithium, carbamazepine and valproic acid had a common mechanism of action on enzymes in the phosphatidylinositol signalling pathway^[10] and the inositol depletion hypothesis for the pathophysiology of bipolar disorder was suggested. Intensive research has so far not confirmed this hypothesis, partly because lithium can also act on a number of other enzymes in this pathway, complicating results from in vitro studies.

Further reading

• Bone R, Springer JP, Atack JR . Structure of inositol monophosphatase, the putative target of lithium therapy . Proc. Natl. Acad. Sci. U.S.A. . 89 . 21 . 10031–10035 . 1992 . 1332026 . 10.1073/pnas.89.21.10031 . 50271 . 1992PNAS...8910031B . free .
• Hallcher LM, Sherman WR . The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain . J. Biol. Chem. . 255 . 22 . 10896–901 . 1981 . 10.1016/S0021-9258(19)70391-3 . 6253491 . free .
• Bone R . Structural analysis of inositol monophosphatase complexes with substrates . Biochemistry . 33 . 32 . 9460–9467 . 1994 . 8068620 . 10.1021/bi00198a011 . Frank L . Springer JP . Pollack . Scott J. . Osborne . Sallyann . Atack . John R. . Knowles . Michael R. . McAllister . George . Ragan . C. Ian .
• Bone R, Frank L, Springer JP, Atack JR . Structural studies of metal binding by inositol monophosphatase: evidence for two-metal ion catalysis . Biochemistry . 33 . 32 . 9468–9476 . 1994 . 8068621 . 10.1021/bi00198a012 .
• Ganzhorn AJ . The contribution of lysine-36 to catalysis by human myo-inositol monophosphatase . Biochemistry . 35 . 33 . 10957–10966 . 1996 . 8718889 . 10.1021/bi9603837 . Lepage P . Pelton PD . Strasser . Françoise . Vincendon . Pascale . Rondeau . Jean-Michel .
• Parthasarathy L, Parthasarathy R, Vadnal R . Molecular characterization of coding and untranslated regions of rat cortex lithium-sensitive myo-inositol monophosphatase cDNA . Gene . 191 . 1 . 81–87 . 1997 . 9210592 . 10.1016/S0378-1119(97)00045-0 .
• Sjøholt G . Genomic structure and chromosomal localization of a human myo-inositol monophosphatase gene (IMPA) . Genomics . 45 . 1 . 113–122 . 1997 . 9339367 . 10.1006/geno.1997.4862 . Molven A . Løvlie R . Wilcox . A . Sikela . JM . Steen . VM .
• Nemanov L . Effect of bipolar disorder on lymphocyte inositol monophosphatase mRNA levels . The International Journal of Neuropsychopharmacology. 2 . 1 . 25–29 . 1999. 11281967 . 10.1017/S1461145799001315 . Ebstein RP . Belmaker RH . Osher . Yamima . Agam . Galila . 16964945 .
• Bahn JH . Production of monoclonal antibodies and immunohistochemical studies of brain myo-inositol monophosphate phosphatase . Mol. Cells . 13 . 1 . 21–7 . 2002 . 11911470 . Kim AY . Jang SH . Lee . BR . Ahn . JY . Joo . HM . Kan . TC . Won . MH . Kwon . HY . 10.1016/S1016-8478(23)14999-5 . free .
• Atack JR, Schapiro MB . Inositol monophosphatase activity in normal, Down syndrome and dementia of the Alzheimer type CSF . Neurobiol. Aging . 23 . 3 . 389–396 . 2002 . 11959401 . 10.1016/S0197-4580(01)00335-9 . 24701473 .
• Berggard T, Szczepankiewicz O, Thulin E, Linse S . Myo-inositol monophosphatase is an activated target of calbindin D28k . J. Biol. Chem. . 277 . 44 . 41954–41959 . 2003 . 12176979 . 10.1074/jbc.M203492200 . free .
• Strausberg RL . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–16903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . Feingold EA . Grouse LH . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M . free .
• Sjøholt G . Examination of IMPA1 and IMPA2 genes in manic-depressive patients: association between IMPA2 promoter polymorphisms and bipolar disorder . Mol. Psychiatry . 9 . 6 . 621–629 . 2005 . 14699425 . 10.1038/sj.mp.4001460 . Ebstein RP . Lie RT . Berle . J Ø . Mallet . J . Deleuze . J F . Levinson . D F . Laurent . C . Mujahed . M . 28747842 .
• Gerhard DS . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–2127 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . Wagner L . Feingold EA . Shenmen . CM . Grouse . LH . Schuler . G . Klein . SL . Old . S . Rasooly . R .
• Rual JF . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–1178 . 2005 . 16189514 . 10.1038/nature04209 . Venkatesan K . Hao T . Hirozane-Kishikawa . Tomoko . Dricot . Amélie . Li . Ning . Berriz . Gabriel F. . Gibbons . Francis D. . Dreze . Matija . 2005Natur.437.1173R . 4427026 .
• Ohnishi T . Spatial expression patterns and biochemical properties distinguish a second myo-inositol monophosphatase IMPA2 from IMPA1 . J. Biol. Chem. . 282 . 1 . 637–646 . 2007 . 17068342 . 10.1074/jbc.M604474200 . Ohba H . Seo KC . Im . J. . Sato . Y. . Iwayama . Y. . Furuichi . T. . Chung . S.-K. . Yoshikawa . T. . free .

External links

• PDBe-KB provides an overview of all the structure information available in the PDB for Human Inositol monophosphatase 1

Notes and References

1. McAllister G, Whiting P, Hammond EA, Knowles MR, Atack JR, Bailey FJ, Maigetter R, Ragan CI . cDNA cloning of human and rat brain myo-inositol monophosphatase. Expression and characterization of the human recombinant enzyme . Biochem J . 284 . 3. 749–54 . Aug 1992 . 1377913 . 1132602 . 10.1042/bj2840749.
2. Web site: Entrez Gene: IMPA1 inositol(myo)-1(or 4)-monophosphatase 1.
3. Vig PJ, Shao Q, Subramony SH, Lopez ME, Safaya E . Bergmann glial S100B activates myo-inositol monophosphatase 1 and Co-localizes to purkinje cell vacuoles in SCA1 transgenic mice . Cerebellum . 8 . 3 . 231–44 . September 2009 . 19593677 . 3351107 . 10.1007/s12311-009-0125-5 .
4. Schmidt H, Schwaller B, Eilers J . Calbindin D28k targets myo-inositol monophosphatase in spines and dendrites of cerebellar Purkinje neurons . Proc. Natl. Acad. Sci. U.S.A. . 102 . 16 . 5850–5 . April 2005 . 15809430 . 556286 . 10.1073/pnas.0407855102 . 2005PNAS..102.5850S . free .
5. Berggard T, Szczepankiewicz O, Thulin E, Linse S . Myo-inositol monophosphatase is an activated target of calbindin D28k . J. Biol. Chem. . 277 . 44 . 41954–9 . November 2002 . 12176979 . 10.1074/jbc.M203492200 . free .
6. Atack JR, Cook SM, Watt AP, Fletcher SR, Ragan CI . In vitro and in vivo inhibition of inositol monophosphatase by the bisphosphonate L-690,330 . J. Neurochem. . 60 . 2 . 652–8 . February 1993 . 8380439 . 10.1111/j.1471-4159.1993.tb03197.x. 23498954 .
7. Atack JR, Prior AM, Fletcher SR, Quirk K, McKernan R, Ragan CI . Effects of L-690,488, a prodrug of the bisphosphonate inositol monophosphatase inhibitor L-690,330, on phosphatidylinositol cycle markers . J. Pharmacol. Exp. Ther. . 270 . 1 . 70–6 . July 1994 . 8035344 .
8. King JS, Teo R, Ryves J, Reddy JV, Peters O, Orabi B, Hoeller O, Williams RS, Harwood AJ . The mood stabiliser lithium suppresses PIP3 signalling in Dictyostelium and human cells . Dis Models Mech . 2 . 5–6 . 306–12 . 2009 . 19383941 . 2675811 . 10.1242/dmm.001271 .
9. Sarkar S, Rubinsztein DC . Inositol and IP3 levels regulate autophagy: biology and therapeutic speculations . Autophagy . 2 . 2 . 132–4 . 2006 . 16874097 . 10.4161/auto.2387. free .
10. Williams RS, Cheng L, Mudge AW, Harwood AJ . A common mechanism of action for three mood-stabilizing drugs . Nature . 417 . 6886 . 292–5 . May 2002 . 12015604 . 10.1038/417292a . 2002Natur.417..292W . 4302048 .