Metabolism of lysopolyphosphoinositides by rat brain and liver microsomes.
Lysophosphatidylinositol 4,5-bisphosphate has been reported to form ion-conducting channels in artificial membranes. If formed in vivo, mechanisms for its removal from cellular membranes would be required. Thus, possible pathways were explored in rat brain and liver microsomes. Since neither lysophosphatidylinositol 4-phosphate nor lysophosphatidylinositol 4,5-bisphosphate were acylated in experiments with [3H]arachidonic acid or [14C]oleoyl CoA, polyphosphoinositides do not participate directly in a deacylation-reacylation cycle as proposed for the postsynthesis enrichment of phosphatidylinositol with arachidonic acid. Similar enrichment in polyphosphoinositides can occur only via the rapid phosphorylation-dephosphorylation cycle linking all three phosphoinositides. Lysophosphatidyl[2-3H]inositol 4,5-bisphosphate and lysophosphatidyl[2-3H]inositol 4-phosphate were rapidly dephosphorylated to 1-acyl-sn-glycero(3)phospho(1)-D-myo-inositol by microsomes from both tissues. Appearance of only trace quantities of radioactive lysophosphatidylinositol monophosphate during the catabolism of lysophosphatidyl[2-3H]inositol 4,5-bisphosphate indicated that the second dephosphorylation step, which was cation independent, was at least as fast as the first step which required Mg2+. In the presence of ATP, CoA, and arachidonic acid, the lysophosphatidylinositol was converted to phosphatidylinositol. This acylation reaction was rate limiting in brain microsomes. Dephosphorylation of lysophosphatidylinositol 4,5-bisphosphate was rate limiting in liver microsomes. Neither the lysopolyphosphoinositides nor the lysophosphatidylinositol produced from them in the reactions were degraded by acyl hydrolases or phosphodiesterases in microsomes from either tissue. Therefore, any lysopolyphosphoinositide formed in vivo would probably be removed by dephosphorylation and recycled to phosphatidylinositol.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D007700:Kinetics; D008861:Microsomes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D051381:Rats; D014316:Tritium
D001095:Arachidonic Acids; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D014316:Tritium; D016718:Arachidonic Acid; D010744:Phosphoric Monoester Hydrolases