Asymmetric phospholipids bilayer

Our present ideas about the nature of biological membranes, which are so fundamental to all biochemical processes, are based on the Singer-Nicholson mosaic model. This model of the membrane is based on a phospholipid bilayer that is, however, asymmetrical. In the outside monolayer, phosphatidylcholine (lecithin) predominates, whereas the inner monolayer on the cytoplasmic side is rich in a mixture of phos-phatidylethanolamine, phosphatidylserine, and phosphatidylinositol. Cholesterol molecules are also inserted into the bilayer, with their 3-hydroxyl group pointed toward the aqueous side. The hydrophobic fatty acid tails and the steran skeleton of cholesterol... 

Tab. 4.32 Molecular parameters describing the (glyco)lipids constituting the bilayer leaflet at the side of PMB addition of various asymmetric planar bilayers (the second leaflet was always made from the phospholipid mixture) and the average diameters of the induced membrane lesions. (Reprinted from Tab. 1 of ref. 117 with permission from Bertelsmann-Springer.)...

The outer membrane (OM) is an asymmetric lipid bilayer, with an inner leaflet composed of phospholipids and an outer leaflet composed of lipopolysaccharide (O Fig. 1) [6]. The phospholipid composition of the inner leaflet of the OM of E. coli is similar to that of the inner membrane predominantly phosphatidylethanolamine, with smaller amounts of phosphatidyl-... 

Proteins that can flip phospholipids from one side of a bilayer to the other have also been identified in several tissues (Figure 9.11). Called flippases, these proteins reduce the half-time for phospholipid movement across a membrane from 10 days or more to a few minutes or less. Some of these systems may operate passively, with no required input of energy, but passive transport alone cannot establish or maintain asymmetric transverse lipid distributions. However, rapid phospholipid movement from one monolayer to the other occurs in an ATP-dependent manner in erythrocytes. Energy-dependent lipid flippase activity may be responsible for the creation and maintenance of transverse lipid asymmetries. 

Because membranes components participate in nearly every cell activity their structures are also dynamic and far from the equilibrium states that are most readily understood in biophysical terms. Newly synthesized bilayer lipids are initially associated with endoplasmic reticulum (Ch.3) whereas phospholipids initially insert into the cytoplasmic leaflet while cholesterol and sphingolipids insert into the luminal endoplasmic reticulum (ER) leaflet. Glycosylation of ceramides occurs as they transit the Golgi compartments, forming cerebrosides and gangliosides in the luminal leaflet. Thus, unlike model systems, the leaflets of ER membranes are asymmetric by virtue of their mode of biosynthesis. 

In general the sphingolipids are located on the exterior face of a membrane while the phospholipids make up the inner face. This is understandable when we recall that sphingolipids include the gangliosides and cerebrosides whose polar ends contain carbohydrates or complex carbohydrate derivatives. The large number of chiral centers in carbohydrate molecules offer a complex pattern on the surface of the membrane which can impart a large degree of specificity for a particular cell type. The composition and limited fluidity of the bilayer make the entire membrane asymmetric, that is, different on the inner and outer layers or leaflets. 

As an example of an asymmetric membrane integrated protein, the ATP synthetase complex (ATPase from Rhodospirillum Rubrum) was incorporated in liposomes of the polymerizable sulfolipid (22)24). The protein consists of a hydrophobic membrane integrated part (F0) and a water soluble moiety (Ft) carrying the catalytic site of the enzyme. The isolated ATP synthetase complex is almost completely inactive. Activity is substantially increased in the presence of a variety of amphiphiles, such as natural phospholipids and detergents. The presence of a bilayer structure is not a necessary condition for enhanced activity. Using soybean lecithin or diacetylenic sulfolipid (22) the maximal enzymatic activity is obtained at 500 lipid molecules/enzyme molecule. With soybean lecithin, the ATPase activity is increased 8-fold compared to a 5-fold increase in the presence of (22). There is a remarkable difference in ATPase activity depending on the liposome preparation technique (Fig. 41). If ATPase is incorporated in-... 

Lipids also show asymmetrical distributions between the inner and outer leaflets of the bilayer. In the erythrocyte plasma membrane, most of the phosphatidylethanolamine and phosphatidylserine are in the inner leaflet, whereas the phosphatidylcholine and sphingomyelin are located mainly in the outer leaflet. A similar asymmetry is seen even in artificial liposomes prepared from mixtures of phospholipids. In liposomes containing a mixture of phosphatidylethanolamine and phosphatidylcholine, phosphatidylethanolamine localizes preferentially in the inner leaflet, and phosphatidylcholine in the outer. For the most part, the asymmetrical distributions of lipids probably reflect packing forces determined by the different curvatures of the inner and outer surfaces of the bilayer. By contrast, the disposition of membrane proteins reflects the mechanism of protein synthesis and insertion into the membrane. We return to this topic in chapter 29. 

Artificial asymmetric membranes composed of outer membranes of various species of Gram-negative bacteria and an inner leaflet of various phospholipids have been prepared using the Montal-Mueller technique [65]. Such planar bilayers have been used, for example, to study the molecular mechanism of polymyxin B-mem-brane interactions. A direct correlation between surface charge density and self-promoted transport has been found [66]. 

Figure 9.24 also distinguishes between the phospholipids on the plasma and cytosol surfaces of the bilayer. Most membranes are asymmetric in this respect phosphoglycerides on the cytosol side are largely anionic—phosphatidylserine,... 

Question Vesicles made from a mixture of phospholipids have an asymmetric distribution of the lipids between the two leaves of the bilayer. Why is this so ... 

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