Enzyme - Inositol-phosphate phosphatase

Alternative Name(s)
  • Myo-inositol monophosphatase.
  • Inositol phosphatase.
  • Myo-inositol-1(or 4)-monophosphatase.
  • Myo-inositol 1-phosphatase.
  • Myo-inositol-1(or 4)-phosphate phosphohydrolase.
  • Myo-inositol-1-phosphatase.
  • Inositol monophosphate phosphatase.
  • Inositol-1(or 4)-monophosphatase.
  • L-myo-inositol-1-phosphate phosphatase.
  • Inositol 1-phosphatase.

Catalytic Activity

myo-inositol phosphate + H2O = myo-inositol + phosphate


There are no Cofactors for this Enzyme

Reaction Mechanism

    Mammalian brain inositol monophosphatase (IMPase) provides inositol for the biosynthesis of the key secondary messenger precursor, phosphatidylinositol 4,5-bisphosphate. Phosphatidylinositol 4,5-bisphosphate is hydrolysed by phosphatidylinositidase C in response to receptor occupation to give diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (Ins 1,4,5-P3), both of which mediate signal transduction through specific interactions with their own targets. DAG activates protein kinase C which modulates the activity of many enzymes through phosphorylation, while Ins 1,4,5-P3 causes the release of calcium ions from an intracellular store. Brain cells vary in their ability to take up inositol and a series of phosphatases exist to sequentially hydrolyse Ins 1,4,5-P3 and other inositol polyphosphates via the bisphosphates to give inositol 1- and 4-monophosphates, substrates for IMPase. The effect of blocking IMPase with inhibitor Li+ cations is depletion of free inositol in brain cells and, thus, several groups have suggested that IMPase might be the target for the lithium ions in manic depression therapy.

    Two Mg(II) ions bind to the enzyme. A water bound to Mg(II), aided by the phosphoryl group of the reactant forms an attacking nucleophilic hydroxide ion to cleave the phosphate-inositolate bond. Subsequent proton transfer steps occur to eliminate the products, myo-inositol and an inorganic phosphate enabling the active site to be ready for another round of catalysis. It has been observed Lithium is a powerful inhibitor of the enzyme due to binding to where one of the magnesium ions usually is found, preventing the phosphate group from leaving.
    Catalytic Residues
    AA Uniprot Uniprot Resid PDB PDB Resid
    Ile P29218 92 1ima 92
    Asp P29218 90 1ima 90
    Asp P29218 220 1ima 220
    Asp P29218 93 1ima 93
    Glu P29218 70 1ima 70
    Thr P29218 95 1ima 95
    Step Components

    overall reactant used, proton transfer, overall product formed, intermediate formation, bimolecular nucleophilic substitution, intermediate terminated, native state of enzyme regenerated, proton relay, dephosphorylation, intermediate collapse

    Step 1.

    The phosphoryl oxygen on the myo-inositol phosphate is protonated by a water molecule. This activates the water to then nucleophilically attack the phosphorous atom causing the phosphate bond to break. It is thought that proton transfer and the Sn2 reaction occur simultaneously.

    Step 2.

    A phosphoryl hydroxide ion donates a proton to Glu70. The magnesium ion stabilises the oxyanion negative charge.

    Step 3.

    Glu70 rotates and protonates the oxyanion intermediate via a water molecule to form the final product, myo-inositol. The water molecule maintains its coordination with a magnesium ion.


    The products of the reaction.

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Protein name Organism
Inositol monophosphatase 2 Human
Inositol-1-monophosphatase SuhB Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Phosphatidylinositide phosphatase SAC2 Human
Putative inositol monophosphatase 3 Fruit fly
Inositol monophosphatase Common ice plant