Noncompetitive inhibition of inositol monophosphatase by K-76 monocarboxylic acid.

K-76COONa, a fungal product that was previously isolated for its inhibition of complement activation, was found to inhibit myo-inositol monophosphatase activity. K-76COONa was slightly more potent than lithium, with a Ki of approximately 0.5 mM. Kinetic analyses with D-myo-inositol 1-phosphate as the substrate showed that myo-inositol monophosphatase inhibition by K-76COONa was noncompetitive relative to substrate but competitive with activation by magnesium. Higher concentrations of K-76COONa were necessary to inhibit myo-[3H]inositol 1,4-bisphosphate hydrolysis by inositol 1,4-bisphosphate/inositol 1,3,4-trisphosphate 1-phosphatase (IC50 = approximately 7.5 mM). K-76COONa may be useful for further investigation of the mechanism of myo-inositol monophosphatase and for determination of whether inhibition of this enzyme plays a role in the therapeutic effectiveness of lithium in treatment of affective disorders.