CHARACTERIZATION OF INOSITOL MONOPHOSPHATASE IN HUMAN CEREBROSPINAL-FLUID

Inositol monophosphatase (IMPase) has been identified and characterized in human lumbar cerebrospinal fluid (CSF). The CSF enzyme has a K(m) for inositol 1-phosphate (Ins(1)P; 0.12 mM), a magnesium dependence (optimum concentration 10 mM) and a sensitivity to inhibition by either the bisphosphonate inhibitor 1-(4-hydroxyphenyloxy)ethane-1,1-bisphosphonic acid (L-690,330) or LiCl (IC50's: 1.3 muM and 1.6 mM, respectively) similar to native human brain and human recombinant enzymes. In CSF, antiserum raised against purified bovine brain IMPase recognised a protein of 30 kDa, identical to that seen in human brain homogenate. It remains to be determined whether CSF IMPase activity may be a useful in vivo marker of CNS phosphatidyl inositol cycle activity in disorders where this signalling pathway may be altered (e.g. manic depression).