Phosphatidylinositols

Phosphatidylinositols are a family of glycerophospholipids that contain myo-inositol as the polar head group, attached to a diacylglycerol backbone via a phosphodiester linkage. They are essential components of eukaryotic membranes and participate in signaling and membrane trafficking. The inositol ring can be phosphorylated at various positions to form phosphatidylinositol phosphates (PIPs), such as PI(4)P, PI(4,5)P2, and PI(3,4,5)P3, with the phosphorylation pattern determining protein interactions and enzyme activity.

Biosynthesis begins with the formation of phosphatidylinositol from CDP-diacylglycerol and myo-inositol by PI synthase. Subsequent phosphorylation by specific kinases yields PIPs: PI 4-kinase produces PI(4)P, PI 4-phosphate 5-kinase generates PI(4,5)P2, and PI3-kinases can convert PI(4,5)P2 to PI(3,4,5)P3. PI(4,5)P2 can be cleaved by phospholipase C to generate IP3 and DAG, linking lipid signaling to calcium signaling and protein kinase cascades. Lipid turnover is tightly regulated by phosphatases and lipid phosphatases, including PTEN and SHIP family members.

Localization and function are largely at the cytosolic face of membranes, particularly the plasma membrane and organelles. PIPs serve as docking sites for proteins with lipid-binding domains such as PH, PX, or ENTH domains, directing membrane trafficking, cytoskeletal organization, and vesicle formation. The specific distribution of PIPs influences signaling outcomes and protein recruitment.

Clinical and physiological relevance stems from the central role of phosphoinositide signaling in growth, metabolism, and cellular organization. Dysregulation of PI and PIP metabolism is associated with cancer, metabolic disorders, and neurodegenerative diseases.