Biochemical and molecular properties of lithium-sensitive myo-inositol monophosphatase
| Autor: | C. S. Shyamala Devi, L. Parthasarathy, Robert Vadnal, Ranganathan Parthasarathy |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
chemistry.chemical_classification
biology Stereochemistry Protein subunit Molecular Sequence Data Phosphatase Active site General Medicine Lithium Phosphoric Monoester Hydrolases General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Enzyme Biochemistry chemistry Enzyme inhibitor Second messenger system biology.protein Animals Humans Inositol Amino Acid Sequence General Pharmacology Toxicology and Pharmaceutics Uncompetitive inhibitor |
| Zdroj: | Life Sciences. 54:1127-1142 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/0024-3205(94)00835-3 |
| Popis: | Myo-inositol monophophatase 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. |
| Databáze: | OpenAIRE |
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