Biological Membranes - A. N. Ogurtsov 2012

Structure and Functions of Biomembranes
Structure of Lipid Membranes
Distribution of lipids between the cytosolic and exoplasmic faces of the membrane

Asymmetry in lipid distribution within the membrane is a characteristic feature of all membrane types. Although most Lipids are present in both monolayers of the bilayer, their concentration in one monolayer is typically much higher than in the other. For instance, in human erythrocyte Plasma Membranes, virtually all sphingomyelins and phosphatidylcholines (both of which form relatively less fluid bilayers) are found exclusively within the monolayer on the exoplasmic face of the membrane.

Conversely, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol (which form more fluid bilayers) are predominantly localized in the cytosolic monolayer of the membrane. This asymmetric lipid distribution between the bilayer monolayers can influence membrane curvature (Figure 27).

Unlike Phospholipids, Cholesterol is distributed almost equally between both monolayers of the membrane bilayer.

The relative Abundance of specific phospholipids can be determined by analyzing the products of their Hydrolysis by phospholipase Enzymes, which cleave specific bonds within the hydrophilic polar heads of phospholipids (Figure 28). Each type of phospholipase cleaves a distinct bond (indicated by arrows in Figure 28). When phospholipases are added to the extracellular space, they cannot hydrolyze phospholipids on the cytosolic face of Cell/30.html">The Plasma Membrane because they are unable to cross the membrane and access the Cytosol. Phospholipase C (PLC) (Figure 28) is cytosolic and hydrolyzes phospholipids on the cytosolic side of the plasma membrane, leaving diacylglycerol embedded in the membrane (Figure 15(6)).

Currently, the mechanisms underlying the asymmetrical distribution of phospholipids within membranes remain unclear. In pure lipid bilayers, phospholipids do not spontaneously undergo transbilayer movement (flip-flop) from one monolayer to the other, as this process requires forcing a polar HEAD group through the Hydrophobic core of the membrane, which is energetically extremely unfavorable.

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Figure 28 - Hydrolysis of phospholipids by phospholipases A, C, and D. Numbers indicate the carbon atoms of the glycerol backbone

The asymmetry in phospholipid distribution is likely determined by the vectorial synthesis of lipids within the Endoplasmic reticulum and the Golgi apparatus.

Sphingomyelin is synthesized on the luminal (exoplasmic) surface of the Golgi membrane, whereas phosphoglycerides, by contrast, are synthesized on the cytosolic face of The endoplasmic reticulum membrane, which is topologically equivalent to the cytosolic side of the plasma membrane.

However, this hypothesis does not fully account for the preferential localization of phosphatidylcholine on the exoplasmic leaflet of the membrane.

The translocation of this and other lipid types from one membrane monolayer to the other is catalyzed by specialized ATP-dependent transport Proteins known as flippases.

The selective localization of lipids to one side of the membrane is physiologically essential for numerous membrane-mediated processes. For example, the polar head groups of all phosphorylated forms of phosphatidylinositol (PI) are oriented toward The Cell cytosol. Some of these head groups are cleaved by cytosolic phospholipase C, which is activated in response to the action of various Hormones on the cell.

The action of phospholipase C results in the release of Water-soluble phosphoinositol (IP) into the cytosol, while lipophilic diacylglycerol (DAG) remains retained within the membrane (Figure 15(6)). These molecules play crucial roles in Intracellular Signaling pathways.

Phosphatidylserine is also predominantly located in the cytosolic monolayer of the plasma membrane. During the Cytology/cytology/16.html">Early stages of platelet stimulation by Blood serum, phosphatidylserine is transiently translocated to the exoplasmic face of the membrane (presumably via flippase activity), where it activates enzymes essential for Blood Coagulation.