Lipid asymmetry

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. 

The mechanisms involved in the establishment of lipid asymmetry are not well understood. The enzymes involved in the synthesis of phospholipids are located on the cytoplasmic side of microsomal membrane vesicles. Translocases (flippases) exist that transfer certain phospholipids (eg, phosphatidylcholine) from the inner to the outer leaflet. Specific proteins that preferentially bind individual phospholipids also appear to be... 

Tsui, F.C., Sundberg, S.A. and Hubbell, W.L., 1990, Distribution of charge on photoreceptor disc membranes and implications for charged lipid asymmetry. Biophys. J. 57 85-97. 

In many eukaryotic plasma membranes, PS resides in the inner leaflet (Schroit and Zwaal, 1991 Zachowski, 1993). This transbilayer distribution of membrane hpids is not a static situation but a result of balance between the inward and outward translocation of phospholipids across the membranes. Recent studies showed that the transbilayer lipid asymmetry is regulated by several lipid transporter proteins, such as aminophospholipid translocase (Daleke and Lyles, 2000), ATP-binding cassette transporter family (van Helvoort et al, 1996 Klein et al, 1999), and phospholipid scramblase (Zhou et al, 1997 Zhao et al, 1998). An increment of intracellular due to cell activation, cell injury, and apoptosis affects the activities of these transporters, resulting in exposure of PS (Koopman et al, 1994 Verhoven et al, 1995) and PE (Emoto et al, 1997) on the cell surface. 

LIPID PHASE TRANSITION KINETICS Membrane lipid asymmetry,... 

The biological function of lipid asymmetry and of proteins involved in the transmembrane traffic of lipids is multiple. Rapid reorientation of phospholipids in ery-... 

In the case of red blood cells, it is assumed that the progressive loss of lipid asymmetry, possibly associated with the entry of calcium, is a signal that the cell is aging. This signal, in turn, is recognized by macrophages and leads to cell destruction. Dmgs which, for example, compete for calcium bound to phosphatidylserine could interfere with these processes and many other Ca2+-dependent processes such as protein kinase C activation. The influence of asymmetry in membranes of different phospholipid composition on the fusion of liposomes has been studied and reported [22]. 

Zachowski, A., Henry, J.P. and Devaux, P.F., 1989, Control of transmembrane lipid asymmetry in chromaffin granules by an ATP-dependent protein. Nature, 340 75-76... 

Crane JM, Kiessling V, Tamm LK. Measuring lipid asymmetry in planar supported bilayers by fluorescence interference contrast microscopy. Langmuir 2005 21 1377-1388. 

P.F. Devaux. 1992. Protein involvement in transmembrane lipid asymmetry Annu. Rev. Biophys. Biomol. Struct 21 417-439. (PubMed)... 

NMR is a valuable technique in the analysis of lipid phases. More specifically, proton, deuterium, carbon-13, fluorine-19, and phosphorus-31 NMR have been utilized for analysis of the dynamic and motional properties of lipids, lipid diffusion, ordering properties, head-group hydration, lipid asymmetry, quantitation of lipid composition, and head-group conformation and dynamics. Cullis et al. and Gruner et al. have shown the importance of P-31 NMR as a tool in the determination of phase properties and lipid asymmetry and the identification of bilayer, hexagonal, and isotropic phases. 

Asymmetry in the lipid distribution over the bilayer could also be controlled in a similar way by the lateral packing pressure, which is likely to differ between constituent monolayers, due to the distinct chemical environments inside and outside the membrane. The enzymes involved may also be distributed asymmetrically. A configuration with constant, but nonzero, mean curvature, shown in Fig. 5.7, reflects such a situation. A membrane-spatming protein can then be viewed as a sensor of the lateral packing pressure in both monolayers. This speculation has some experimental justification. In a recent study of chromaffin granules, trans-membrane lipid asymmetry was shown to be induced by an ATP-dependent "flippase" [35]. 

Devaux PF. 8tatic and dynamic lipid asymmetry in cell membranes. Biochemistry 1991 30 1163-1173. Dratz EA, Deese AJ. The role of docosahexaenoic acid (22 6w3) in biological membranes examples from... 

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... 

Acyl lipid asymmetry during oat thylakoid development... 

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