Phospholipid asymmetrical distribution

While examples such as these provide evidence that strong interactions of negatively-charged membrane lipids with membrane proteins the role in maintaining asymmetric distributions of lipids aaoss biological membranes is unclear. In any event such effects are likely to be of minor importance relative to actively mediated phospholipid translocation processes. 

Asymmetric distribution of phospholipids across the retinal rod outer segment disk membrane has been shown to be associated with light reception by rhodopsin. It is known that the major phospholipids of this membrane, phosphatidylcholine and phosphatidylethanolamine, are symmetrically distributed across the membrane in the dark but not... 

The maintenance of an asymmetric distribution of phospholipids across the plasma membrane with choline phospholipids predominating on the external surface and amino phospholipids confined to the cytoplasmic leaflet of the membrane has now been well estabhshed. The participation of... 

Seigneuret, M., and Devaus, P. R, ATP-dependent asymmetric distribution of spin-labeled phospholipids in the erythrocyte membrane Relation to shape change. Proc. Natl. Acad. Sci. U.S.A. 81, 3751-3755 (1984). 

FIGURE 11-5 Asymmetric distribution of phospholipids between the inner and outer monolayers of the erythrocyte plasma membrane. 

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. 

The negatively charged phospholipid phosphatidylserine is asymmetrically distributed in mammalian cell membranes, primarily on the inner leaflet. Upon exposure to collagen or thrombin, the distribution of phospholipids changes with increasing phosphatidylserine in the external membrane leaf (I). The increased expression of phosphatidylserine on the outer leaflet of the membrane creates a procoagulant surface on which several steps of the coagulation cascade take place. 

Tab. 1.4 Asymmetrical distribution of phospholipids (mol%) in membranes of influenza viruses [13] and in red blood cells [12]...

Verkleij, A.J., Zwaal, R.F., Roelofsen, B., Comfurius, P., Kastelijn, D. and van Deenen, L.L.M., 1973, The asymmetric distribution of phospholipids in the human red cell membrane. A combined study using phospholipases and freeze-etch electron microscopy. 

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 ... 

Carbohydrate residues are covalently linked (exclusively on the external side of the bilayer) to proteins or lipids to form glycoproteins or glycolipids, respectively, both of which are asymmetrically distributed in the lipid bilayer (Figure 10-7). Fluidity of the membrane structure is determined by the degree of unsaturation of the hydrocarbon chains of the phospholipids and by the amount of cholesterol in the membrane. Hydrocarbon chains... 

Phospholipids are asymmetrically distributed in the lipid bilayer, with phosphatidylethanolamine predominating on the matrix side and phosphatidylcholine on the cytoplasmic side. Seventy-five percent of the cardiolipin is present on the matrix side of the membrane. The fatty acid composition of the phospholipids depends on the species, tissue, and diet. In all cases, sufficient unsaturated fatty acids are contained in the phospholipids to provide a highly fluid membrane at physiological temperatures. 

Lipid transfer proteins have proved to be a useful tool for studying artificial and natural membranes (for a recent review see Bloj and Zilver-smit, 1981a). With the ability of phospholipid transfer proteins to replace selectively the phospholipid molecules on the exposed surfaces of membranes, information about the asymmetric distribution of phospholipids across a bilayer and the rate of transbilayer movement of phospholipid... 

Knowledge of the size of the exchangeable pool of lipid in a substrate is necessary to determine the rate constants of the exchange process and establish the specificity of a transfer protein for different classes of phospholipids. The size of the exchangeable pool of each class of phospholipid must be determined individually because phospholipids are often asymmetrically distributed across biological and artificial membranes (Op den Kamp, 1979). 

The exchangeable lipid pool in a donor particle can be determined by measuring the labeled lipid remaining in the donor membrane after prolonged incubation of radiolabeled donor membranes with an excess of acceptor particles and transfer protein (Zilversmit and Hughes, 1976). This technique has also been used to determine the asymmetric distribution of phospholipid molecules and their rate of transbilayer movement... 

A novel catalyst consisting of colloidal palladium adsorbed onto the surface of a water-insoluble polymer, polyvinylpyrrolidone, has been shown to hydrogenate only the outer leaflet of rat platelets [59]. The effect of hydrogenation was to influence the asymmetric distribution of the phospholipids of the membrane. Catalytic hydrogenation of a phytopathogenic fungus [60] has also been reported. 

How the asymmetric distribution of phospholipids in membrane leaflets arises is still unclear. In pure bilayers, phospholipids do not spontaneously migrate, or flip-flop, from one leaflet to the other. Energetically, such flip-flopping is extremely unfavorable because it entails movement of the polar phospholipid head group through the hydrophobic interior of the membrane. To a first approximation, the asym-... 

Different cellular membranes vary in lipid composition (see Table 5-1). Phospholipids and sphingolipids are asymmetrically distributed in the two leaflets of the bilayer, whereas cholesterol is fairly evenly distributed in both leaflets. 

Even though phospholipids are initially incorporated into the cytosolic leaflet of the ER membrane, various phospholipids are asymmetrically distributed in the two leaflets of the ER membrane and of other cellular membranes (see Table 5-1). However, phospholipids spontaneously flip-flop from one leaflet to the other only very slowly, although they can rapidly diffuse laterally in the plane of the membrane. For the ER membrane to expand (growth of both leaflets) and have asymmetrically distributed phospholipids, its phospholipid components must be able to rapidly and selectively flip-flop from one membrane leaflet to the other. 

The usual asymmetric distribution of phospholipids In membrane leaflets Is broken down as cells (e.g., red blood cells) become senescent or undergo apoptosis. For Instance, phosphatidylserine and phosphatidylethanolamlne are preferentially located In the cytosolic leaflet of cellular membranes. Increased exposure of these anionic phospholipids on the exoplasmic face of the plasma membrane appears to serve as a signal for scavenger cells to remove and destroy old or d dng cells. Annexin V, a protein that specifically binds to anionic phospholipids, can be fluorescently labeled and used to detect apoptotic cells In cultured cells and In tissues. 

Phospholipids have polar head groups, so their transfer across the hydrophobic interior of the bilayer as well as their dissociation from water at the bilayer surface would require a positive change in free energy. Without the input of free energy to make the process a spontaneous one, the transfer of the polar head group is very unlikely, so the asymmetric distribution of the phospholipids is preserved. 

Our present view of the cell membrane structure is that it is analogous to a two-dimensional oriented solution of globular lipoproteins dispersed in a discontinuous fluid bilayer of lipid solvent [2]. Phospholipids constitute the bulk of the lipids. Both components of the membrane (proteins and lipid) are free to some degree to have lateral mobility in the plane of the membrane and in some cases are asymmetrically distributed across the two halves of the bilayer [2]. Some proteins are peripherally attached to either of the two faces while other polypeptide chains may span the whole thickness of the membrane [2]. These latter proteins probably correspond to... 

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