In vitro and in vivo inhibitory actions of morin on rat brain phosphatidylinositolphosphate kinase activity.
Phosphatidylinositol-4,5-bisphosphate occupies a central role in signal transduction and in cellular transformation. Phosphatidylinositol-4,5-bisphosphate is produced by the enzymatic phosphorylation of phosphatidylinositol-4-phosphate by phosphatidylinositolphosphate kinase (EC 2.7.1.68). Inhibition of this enzyme might conceivably lowers the cellular pool of phosphatidylinositol-4,5-bisphosphate, thus constituting a feasible control point in regulating signal transduction and cellular transformation. Morin, a plant flavonoid, was demonstrated to exhibit in vitro inhibitory action on phosphatidylinositolphosphate kinase extracted from rat brain. This inhibition of enzymatic activity was found to be dose-dependent, with an IC50 value of approximately 10 microM morin. Lineweaver-Burk transformation of the inhibition data indicates that inhibition was competitive with respect to ATP. The Ki was calculated to be 5.15 x 10(-6) M. Inhibition was uncompetitive with respect to phosphatidylinositol-4-phosphate. The Ki was determined to be 0.94 x 10(-5) M. Administration of morin to rats led to a decrease in phosphatidylinositolphosphate kinase activity in brain extracts. This in vivo action of morin was found to be dose-dependent and time-dependent. These effects of morin on rat brain phosphatidylinositolphosphate kinase activity are discussed in relation to the other reported biological actions of this flavonoid.
Cheng
C H
CH
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, N.T.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D047309:Flavones
D000255:Adenosine Triphosphate; D004791:Enzyme Inhibitors; D005419:Flavonoids; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D017853:Phosphotransferases (Alcohol Group Acceptor); C037178:phosphatidylinositol 4-phosphate; C008548:morin; D047309:Flavones; C020077:1-phosphatidylinositol-4-phosphate 5-kinase