Cell membranes bilayer asymmetry

Membrane proteins have a unique orientation because they are synthesized and inserted into the membrane in an asymmetric manner. This absolute asymmetry is preserved because membrane proteins do not rotate from one side of the membrane to the other and because membranes are always synthesized by the growth of preexisting membranes. Lipids, too, are asymmetrically distributed as a consequence of their mode of biosynthesis, but this asymmetry is usually not absolute, except for glycolipids. In the red-blood-cell membrane, sphingomyelin and phosphatidyl choline are preferentially located in the outer leaflet of the bilayer, whereas phosphatidyl ethanolamine and phosphatidyl serine are located mainly in the inner leaflet. Large amounts of cholesterol are present in both leaflets. 

Asymmetry. Biological membranes are asymmetric that is, the lipid composition of each half of a bilayer is different. For example, the human red blood cell membrane possesses substantially more phosphatidylcholine and sphingomyelin on its outside surface. Most of the membrane s phosphatidylserine and phos-phatidylethanolamine are on the inner side. Membrane asymmetry is not unexpected, because each side of a membrane is exposed to a different environment. Asymmetry originates during membrane synthesis, because phospholipid biosynthesis occurs on only one side of a membrane (Special Interest Box 12.3). The protein components of membranes (discussed below) also exhibit considerable asymmetry with distinctly different functional domains within membrane and on the cytoplasmic and extracellular faces of membrane. 

In addition to the large numbers of chemically distinct lipid species that occur within a prokaryotic or a eukaryotic cell, there is another level of complexity — the asymmetric distribution of the lipids across the plane of the bilayer. Two striking examples of membrane lipid asymmetry were originally described in the red blood cell membrane (A. Verkleij, 1973), and the cytoplasmic membrane of Bacillus megaterium (J. Rothman, 1977). The data in Fig. 1... 

The inner and outer components of the membrane bilayer have been shown to possess differing compositions and this is reflected in the different biological properties of the inside and outside of the cell membranes as reviewed by Bretscher [242]. X-Ray analysis of eukaryotic myelin membranes has demonstrated an asymmetric distribution of sterols, with almost double the sterol content in the outer bilayer leaflet as compared to the inner layer [243], This asymmetry is reflected in Figure 3.4. 

Plasma membrane lipids are asymmetrically distributed between the two monolayers of the bilayer, although the asymmetry, unlike that of membrane proteins, is not absolute. In the plasma membrane of the erythrocyte, for example, choline-containing lipids (phosphatidylcholine and sphingomyelin) are typically found in the outer (extracellular or exoplasmic) leaflet (Fig. 11-5), whereas phosphatidylserine, phosphatidyl-ethanolamine, and the phosphatidylinositols are much more common in the inner (cytoplasmic) leaflet. Changes in the distribution of lipids between plasma membrane leaflets have biological consequences. For example, only when the phosphatidylserine in the plasma membrane moves into the outer leaflet is a platelet able to play its role in formation of a blood clot. For many other cells types, phosphatidylserine exposure on the outer surface marks a cell for destruction by programmed cell death. 

A characteristic of all membranes is an asymmetry in lipid composition across the bilayer. Although most phospholipids are present in both membrane leaflets, they are commonly more abundant in one or the other leaflet. For instance, in plasma membranes from human erythrocytes and certain canine kidney cells grown in culture, almost all the sphingomyelin and phosphatidylcholine, both of which form less fluid bilayers, are found in the exoplasmic leaflet. In contrast, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol, which form more fluid bilayers, are preferentially located in the cytosolic leaflet. This segregation of lipids across the bilayer may influence membrane curvature (see Figure 5-8c). Unlike phospholipids, cholesterol is relatively evenly distributed in both leaflets of cellular membranes. 

AG. The mycolic acids are packed in a monolayer, parallel to each other, and oriented perpendicularly to the plasma membrane. It was further hypothesized that noncovalently linked lipids would intercalate into the outer portion of the mycolic acids layer due to the asymmetry of the two arms of the mycolate. Subsequently, a second model was proposed that was similar, except that the noncovalently linked lipids were proposed to form a monolayer that did not intercalate with the mycolic acids, providing a model that more nearly approximated a cell envelope with two bilayers. Subsequently, experiments showed that the mycolic acids were, in fact, aligned perpendicularly to the cell surface and formed tight crystalline arrays, providing support for the basis of both... 

Bidirectional transporters. The bidirectional transporters at the plasma membrane randomize the lipid distribution across the plane of the bilayer, and are commonly referred to as scramblases [17]. The action of scramblase is summarized in Fig. 5, and is similar to that of the previously described transbilayer transporter present in the ER. Scramblase protein was first functionally identified in erythrocytes but is also present in nucleated cells. The scramblase shows no lipid specificity and essentially collapses the asymmetry of lipids at the cell surface. Phospholipids, SM, and glycosphingolipids all serve as substrates. The randomizing function of the plasma membrane protein is activated by Ca " and does not require ATP. 

The currently accepted structure of B. is the fluid mosaic model. Lipid molecules and membrane proteins are free to diffuse laterally and to spin within the bilayer in which they are located. However, a flip-flop motion from the inner to the outer surface, or vice versa, is energetically unfavorable, because it would require movement of hydrophilic substituents through the hydrophobic phase. Hence this type of motion is almost never displayed by proteins, and it occurs much less readily than translational motion in the case of lipids. Since there is little movement of material between the inner and outer layers of the bilayer, the two faces of the B. can have different compositions. For membrane proteins, this asymmetry is absolute, and, at least in the plasma membrane, different proportions of lipid classes exist in the two monolayers. Attached carbohydrate residues appear to be located only on the noncytosolic surface. Carbohydrate groups extending from the B. participate in cell recognition, cell adhesion, possibly in intercellular communication, and they also contribute to the distinct immunological character of the cell. 

The membranes of cells are generally asymmetric, in that the lipids and proteins that inhabit the membrane are not evenly distributed across both the leaflets of the bilayer. To maintain this necessary membrane asymmetry, transverse diffusion of phospholipids (flip-flop. Figure 6a) in cellular membranes is accelerated by translocase enzymes like the flippases. These enzymes overcome the energy barrier for the passage of polar headgroups through the apolar center of the membrane and maintain asymmetry by the consumption of adenosine triphosphate (ATP). ... 

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