Inositol monophosphatase 1

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Inositol(myo)-1(or 4)-monophosphatase 1
Protein IMPA1 PDB 1awb.png
PDB rendering based on 1awb.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols IMPA1 ; IMP; IMPA
External IDs OMIM602064 MGI1933158 HomoloGene4043 ChEMBL: 1786 GeneCards: IMPA1 Gene
EC number 3.1.3.25
RNA expression pattern
PBB GE IMPA1 203011 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3612 55980
Ensembl ENSG00000133731 ENSMUSG00000027531
UniProt P29218 O55023
RefSeq (mRNA) NM_001144878 NM_018864
RefSeq (protein) NP_001138350 NP_061352
Location (UCSC) Chr 8:
82.57 – 82.6 Mb
Chr 3:
10.31 – 10.33 Mb
PubMed search [1] [2]

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

Interacting partners[edit]

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

Chemical inhibitors[edit]

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[edit]

Initially it was noticed that several drugs useful in treatment of biopolar 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 biopolar 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.

References[edit]

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

Further reading[edit]