Lipid asymmetry is functionally important, especially in converting extracellular signals into intracellular ones (discussed in Chapter 15). Many cytosolic proteins bind to specific lipid head groups found in the cytosolic monolayer of the lipid bilayer. The enzyme protein kinase C (PKC), for example, which is activated in response to various extracellular signals, binds to the cytosolic face of the plasma membrane, where phosphatidylserine is concentrated, and requires this negatively charged phospholipid for its activity.
In other cases, specific lipid head groups must first be modified to create pro-tein-binding sites at a particular time and place. One example is phosphatidylinositol (PI), one of the minor phospholipids that are concentrated in the cytosolic monolayer of cell membranes (see Figure 13–10A–C). Various lipid kinases can add phosphate groups at distinct positions on the inositol ring, creating binding sites that recruit specific proteins from the cytosol to the membrane. An important example of such a lipid kinase is phosphoinositide 3-kinase (PI 3-kinase), which is activated in response to extracellular signals and helps to recruit specific intracellular signaling proteins to the cytosolic face of the plasma membrane (see Figure 15–53). Similar lipid kinases phosphorylate inositol phospholipids in intracellular membranes and thereby help to recruit proteins that guide membrane transport.
Phospholipids in the plasma membrane are used in yet another way to convert extracellular signals into intracellular ones. The plasma membrane contains various phospholipases that are activated by extracellular signals to cleave specific phospholipid molecules, generating fragments of these molecules that act as short-lived intracellular mediators. Phospholipase C, for example, cleaves an inositol phospholipid in the cytosolic monolayer of the plasma membrane to generate two fragments, one of which remains in the membrane and helps activate protein kinase C, while the other is released into the cytosol and stimulates the release of Ca2+ from the endoplasmic reticulum (see Figure 15–28).
Animals exploit the phospholipid asymmetry of their plasma membranes to distinguish between live and dead cells. When animal cells undergo apoptosis (a form of programmed cell death, discussed in Chapter 18), phosphatidylserine, which is normally confined to the cytosolic (or inner) monolayer of the plasma membrane lipid bilayer, rapidly translocates to the extracellular (or outer) mono-layer. The phosphatidylserine exposed on the cell surface signals neighboring cells, such as macrophages, to phagocytose the dead cell and digest it. The trans-location of the phosphatidylserine in apoptotic cells is thought to occur by two mechanisms: 1.
The phospholipid translocator that normally transports this lipid from the outer monolayer to the inner monolayer is inactivated.
2.
A “scramblase” that transfers phospholipids nonspecifically in both directions between the two monolayers is activated.
Figure 10–15 The asymmetrical distribution of phospholipids and glycolipids in the lipid bilayer of human red blood cells. the colors used for the phospholipid head groups are those introduced in Figure 10–3. In addition, glycolipids are drawn with hexagonal polar head groups (blue). cholesterol (not shown) is distributed roughly equally in both monolayers.
glycolipids Are Found on the Surface of All eukaryotic  plasma Membranes