Figure 2. Synthesis and degradation of PI(4,5)P₂ – phospholipase C cycle.

PLC hydrolyses PI(4,5)P₂ resulting in the formation of the second messengers, IP₃ and DAG. DAG is phosphorylated to PA at the plasma membrane by DAG kinase (DAGK). PA is transferred to the ER via lipid transfer proteins. In the ER, PA is converted into CDP-DAG catalysed by CDS enzymes (CDS1 and CDS2). In the final step, inositol and CDP-DAG are synthesised into PI catalysed by the enzyme, PI synthase (PIS). The newly synthesised PI is transferred to the plasma membrane for phosphorylation to PI(4,5)P₂ by the resident enzymes, PI4KIIIα and PIP5K. Abbreviations: CDP-DAG, cytidine diphosphate diacylglycerol; CDS, CDP-DAG synthase; IP₃, inositol(1,4,5)triphosphate; PA, phosphatidic acid; PI, phosphatidylinositol; PIS, PI synthase; PITP, phosphatidylinositol transfer protein; PI4P, PI 4-phosphate; PI(4,5)P₂, phosphatidylinositol (4,5) bisphosphate.