title: Biochemical and molecular properties of lithium-sensitive myo-inositol monophosphatase.
abstract: Myo-inositol monophosphatase is a pivotal enzyme of the inositol second messenger system which is specifically inhibited by therapeutic levels of lithium salts, implicating inhibition of this enzyme as a potential site of its action in bipolar disease. This enzyme has a native molecular weight of 59,000, and has traditionally been found in the cytosolic fraction, although a membrane-bound form has also been identified. Possessing two identical subunits, this enzyme hydrolyzes those monophosphates which are equatorially located within the inositol ring, and several nucleoside monophosphates phosphorylated at the 2-position. Each subunit of the native enzyme contains an active site with unusually large caverns as revealed by crystallographic studies, which may explain the accommodation of these structurally unrelated substrates. We have suggested that the uncompetitive inhibition of this phosphatase by lithium ions may prevent the formation of an enzyme-bound non-isomeric (meso) intermediate, Mg(2+)-inositol 1,3 or 4,6 cyclic monophosphate when this enzyme hydrolyzes its respective isomeric substrates.
authors.affiliation: Department of Biochemistry, University of Madras, India.
authors.forename: L
authors.initials: L
authors.lastname: Parthasarathy
authors.forename: R E
authors.initials: RE
authors.lastname: Vadnal
authors.forename: R
authors.initials: R
authors.lastname: Parthasarathy
authors.forename: C S
authors.initials: CS
authors.lastname: Devi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008094:Lithium / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
chemical_list: D008094:Lithium; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase