Phosphatidylserine lipids

Bell M, Dick J, Buda C. Molecular sedation of fish sperm phospohlipids large amounts of dipolyunsaturated phosphatidylserine. Lipids 1997 32 1085-1091. 

The purple membrane fragments that contained dark-adapted bacteriorhodopsin were used to form reconstituted vesicles with a mixture of phospholipids that contained 80% egg phosphatidyl choline and 20% bovine phosphatidylserine (Lipid Products, Nuttfield, England). The lipids in chloroform and methanol solutions were mixed to the desired composition, dried in a stream of nitrogen, placed in a 0.1-torr... 

Lipids in model systems are often found in asymmetric clusters (see Figure 9.8). Such behavior is referred to as a phase separation, which arises either spontaneously or as the result of some extraneous influence. Phase separations can be induced in model membranes by divalent cations, which interact with negatively charged moieties on the surface of the bilayer. For example, Ca induces phase separations in membranes formed from phosphatidylserine (PS)... 

Discuss the effects on the lipid phase transition of pure dimyris-toyl phosphatidylcholine vesicles of added (a) divalent cations, (b) cholesterol, (c) distearoyl phosphatidylserine, (d) dioleoyl phosphatidylcholine, and (e) integral membrane proteins. 

The major lipid classes are phospholipids and cholesterol the major phospholipids are phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) along with sphingomyelin (Sph). 

We have proposed that vesicle aggregation is probably related to the disposition of pardaxin bound in the phosphatidylserine vesicle lipid bilayer (26). This conclusion is supported by the observation that phosphatidycholine vesicles are not induced to aggregate and that the pardaxin-induced phosphatidylserine vesicle aggregation is affected by charge polarization of the vesicle (26). This suggestion seems to be consistent also with the voltage dependence of fast "pore" activity of pardaxin, the channels which are open only at positive membrane potentials. 

FIGURE 12.4 (A) Diagrammatic representation of the separation of major simple lipid classes on silica gel TLC — solvent system hexane diethylether formic acid (80 20 2) (CE = cholesteryl esters, WE = wax esters, HC = hydrocarbon, EEA = free fatty acids, TG = triacylglycerol, CHO = cholesterol, DG = diacylglycerol, PL = phospholipids and other complex lipids). (B) Diagrammatic representation of the separation of major phospholipids on silica gel TLC — solvent sytem chloroform methanol water (70 30 3) (PA = phosphatidic acid, PE = phosphatidylethanolamine, PS = phosphatidylserine, PC = phosphatidylcholine, SPM = sphingomyelin, LPC = Lysophosphatidylcholine). 

Materials. Egg phosphatidylcholine (PC), bovine brain phosphatidylserine (PS) were obtained from Avanti Polar Lipids Inc. (Birmingham, AL) and cholesterol was from Sigma (St. Louis, MO). Ganglioside GMj, bovine, was obtained from Calbiochem (San Diego, CA). Diethylenetriamine pentaacetic acid distearylamide complex (DPTA-SA) was synthesized according to ref. 17 and nlIn-DTPA-SA was prepared as described (7). This lipophilic radiolabel is not transferred to the serum components from liposomes (unpublished data), nor is it rapidly metabolized in vivo (7). The synthesis of N-(glutaryl)phosphatidylethanolamine(NGPE) has been described (18). Dipalmitoyl deoxyfluorouridine(dpFUdR) was synthesized as described (24). 

ELISA) in which the antibodies bind to a target lipid, which is usually cardiolipin. Platelet antibodies directed to phosphatidylserine and phosphatidylinositol are referred to as anticardiolipin antibodies and their presence is characterized as anti-cardiolipin antibody-thrombosis syndrome (96). 

It has been found that the catalytic activity of PKC is enhanced by a lipid component of the cell membrane, namely phosphatidylserine. This activity is further stimulated by sn-1,2-diacylglycerol. Oleic acid also activates the enzyme in the presence of 1,2-diacylglycerol, and thus it is presumed to mimic phosphatidylserine. In order to identify that modulating binding site for oleic acid on PKC, a photoaffinity analogue was devised. A carbene generating photophore, diazirine was placed in the apolar terminus of the unsaturated fatty acid ligand (30, Fig. 12). The synthesis and the photochemical activation properties were reported by Ruhmann and Wentrup [113]. 

Figure 1. Control of mitochondrial biogenesis by the nuclear genome. Most mitochondrial proteins, including cytochrome c, are nuclear gene products which are subsequently imported into mitochondria. Similarly, most enzymes involved in synthesis of mitochondrial phosphoplipids are encoded in the nuclear genome. Being located in the endoplasmatic reticulum, they synthesize phosphatidylcholine (PtdCho), phosphatidylserine (PtdSer), phosphatidylglycerol (PG) and phosphatidylinositol (Ptdins). The phospholipids are transferred to the outer membrane. The imported lipids then move into the inner membrane at contact sites. Mitochondria then diversify phospholipids. They decarboxylate phosphatidylserine to phosphatidylethanolamine (PtdEtN), but the main reaction is the conversion of imported phosphatidylglycerol to cardiolipin (CL). Cardiolipins localize mainly in the outer leaflet of the inner membrane.

It can be seen from Figure 1 that the choline-containing phospholipids, phosphatidylcholine and sphingomyelin are localized predominantly in the outer monolayer of the plasma membrane. The aminophospholipids, conprising phosphatidylethanolamine and phosphatidylserine, by contrast, are enriched in the cytoplasmic leaflet of the membrane (Bretcher, 1972b Rothman and Lenard, 1977 Op den Kamp, 1979). The transmembrane distribution of the minor membrane lipid components has been determined by reaction with lipid-specific antibodies (Gascard et al, 1991) and lipid hydrolases (Biitikofer et al, 1990). Such studies have shown that phosphatidic acid, phosphatidylinositol and phosphatidylinositol-4,5-fc -phosphate all resemble phosphatidylethanolamine in that about 80% of the phospholipids are localized in the cytoplasmic leaflet of the membrane. 

Methods used to demonstrate the existence of membrane phospholipid asymmetry, such as chemical labelling and susceptibility to hydrolysis or modification by phospholipases and other enzymes, are rmsuitable for dynamic studies because the rates of chemical and biochemical reactions are of a different order compared to the transmembrane translocahon of the phospholipids. Indirect methods have therefore been developed to measure the translocation rate which are consequent on the loss of membrane phospholipid asymmetry. Thus time scales appropriate to rates of lipid scrambling under resting conditions or when the forces preserving the asymmetric phospholipid distribution are disturbed can be monitored. Generally the methods rely on detecting the appearance of phosphatidylserine on the surface of cells. Methods of demonstrating Upid translocation in mammalian cells has been the subject of a recent review (Bevers etal., 1999). 

Annexin V is a human placental anticoagulant protein of molecular weight 35kDa that binds to membranes and lipid bilayers containing phosphatidylserine in the presence of free calcium. Annexin V binding to cell surfaces said to result from transmembrane movement of... 

Once synthesized several factors influence the particular leaflet of the membrane lipid bilayer where the lipids reside. One is static interactions with intrinsic and extrinsic membrane proteins which, by virtue of their mechanism of biosynthesis, are also asymmetric with respect to the membrane. The interaction of the cytoplasmic protein, spectrin with the erythrocye membrane has been the subject of a number of studies. Coupling of spectrin to the transmembrane proteins, band 3 and glycophorin 3 via ankyrin and protein 4.1, respectively, has been well documented (van Doit et al, 1998). Interaction of spectrin with membrane lipids is still somewhat conjectural but recent studies have characterized such interactions more precisely. O Toole et al. (2000) have used a fluorescine derivative of phosphatidylethanolamine to investigate the binding affinity of specttin to lipid bilayers comprised of phosphatidylcholine or a binary mixture of phosphatidylcholine and phosphatidylserine. They concluded on the basis... 

Fabisiak, J.P., Tyuiin, V.A., Tyurina, Y.Y., Sedlov, A., Lazo, J.S., and Kagan, V.E., 2000, Nitric oxide dissociates lipid oxidation from apoptosis and phosphatidylserine externalization during oxidative stress. Biochemistry 39 127-138. 

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