Fig. 1. Simplified version of the phosphatidylinositol cycle. Inositol is obtained from nutritional sources or de novo synthesis (not shown) or it is recovered from inositol trisphosphate [Ins(1,4,5)P₃] by a salvage pathway that involves sequential dephosphorylation of inositol phosphates by the enzymes inositol polyphosphate phosphatase (IPPase; indicated as step 1) and inositol monophosphate phosphatase (IMPase; step 2), both of which are inhibited by lithium. Phosphatidylinositol (PtdIns) is synthesized from inositol and CDP-diacyglycerol (CDP-DAG). Phosphatidylinositol is monophosphorylated to form PtdIns(4)P by type III PtdIns 4-kinase (step 3), which is inhibited by wortmannin (WT) and LY294002 (LY). PtdIns(4)P is phosphorylated by PtdIns(4)P 5-kinase to form phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P₂]. This in turn, is hydrolyzed by phospholipase C (PLC; step 4) to form Ins(1,4,5)P₃ and DAG in a reaction inhibited by U73122. DAG is then converted to phosphatidic acid (PA) and then CDP-DAG to complete the cycle. Note that WT and LY also inhibit PtdIns 3-kinase (not shown) and that a second type of PtdIns 4-kinase, the type II enzyme, is not inhibited by WT or LY.