Phosphatidylethanolamine functions

Fig. 12.5. Schematic summary of the eight T. canis proteins containing predicted SXC (NC6) domains. The consensus is shown in the N-terminal domain of PEB-1 (phosphatidylethanolamine-binding protein-1) as xCxDxxxDC(6x)C(11x) RCxxTCxxC. This consensus is faithfully repeated in MUC-1 (mucin-1), MUC-2, MUC-4 and MUC-5, and in all but the C-terminal domain of MUC-3. This domain (and the C-terminal SXC domain of PEB-1) show consensus spacing but some variation in consensus residues. Two additional proteins with quadrupled SXC domains differ in spacing between cysteines-2, -3 and -4, and show more variation in consensus residues. These are VAH-1 (venom allergen homologue) and HUF-001 (homologue of unknown function-001).

Figure 2 Structure of functionalized anchors and heterobifunctional reagents. DPPE is given as an example. Abbreviations DPPE, l,2-dipalmitoyl-sn-glycero-3-phos-phoethanolamine DPPE-AcBr, bromoacetyl dipalmitoyl phosphatidylethanolamine.

Although the role of lipid composition in membrane function is not entirely understood, changes in composition can produce dramatic effects. Researchers have isolated fruit flies with mutations in the gene that encodes ethanolamine kinase (analogous to choline kinase Fig. 21-28). Lack of this enzyme eliminates one pathway for phosphatidylethanolamine synthesis, thereby reducing the amount of this lipid in cellular membranes. Flies with this mutation—those with the genotype easily shocked—exhibit transient paralysis following electrical stimulation or mechanical shock that would not affect wild-type flies. 

The EFA are found predominantly within the epidermal phospholipids (e.g., phosphatidylinositol, phosphatidylcholine, phosphatidylethanolamine), with the pattern of incorporation varying between fatty acids. They are also present in small amounts in cholesterol, and importantly, are found linked with ceramides in the granular layer and stratum corneum, where they play a critical role in barrier function. The most abundant EFA in the skin are LA and A A, comprising approximately 12 and 3.5%, respectively of human epidermal fatty acids.12 ALA is known to accumulate in the skin of animals, but is found in much lower levels than LA.13... 

The exact function of the annexin fold family is at present unclear. All of these proteins appear to show calcium-dependent binding to phosphatidylethanolamine or phosphatidylinositol liposomes. In addition, they can promote fusion of liposomes, and because of this property, it has been suggested that these proteins might mediate calcium dependent exocytosis. P36 and p35 have also been shown to bind to F-actin and spectrin [65,66]. Recently, Khanna et al. [70] have reported a procedure for the simultaneous purification of p35, p36 oligomer and p36 monomer from bovine lung, and identified all three proteins as substrates of protein kinase C. Furthermore, the work of Huang et al. [86] and Khanna et al. [69] has suggested that all three proteins are inhibitors of phospholipase A2. Further experiments will be required to clarify the function of these proteins. 

Other functional liposomes are mainly stimuli-responsive liposomes. The pH-sensitive liposomes contain pH-sensitive lipids such as l,2-dioleoyl-vn-3-phosphatidylethanolamine (DOPE) showing an inverted hexagonal configuration in a low-pH environment and release entrapped drugs in the low-pH environment of tumor tissues due to liposomal membrane destabilization [89], Temperature-sensitive liposomes are prepared from special lipids such as DPPC whose phase transition temperature (Tc = 41°C) is proper to perform clinical anticancer therapy. When up to Tc, the fluidity of liposomal membranes increases sharply, followed by... 

Polar lipids. Polar lipids, mainly phospholipids, are present in fats and oils, and these originate primary as components of cell membranes and serve biological functions in the cells. Among phosphohpids present are phosphotidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). In general, saturated fatty acids are present at the sn-1 and unsaturated fatty acids at the sn-2 positions of phosphohpid molecules. 

Lecithin, an edible by-product of oil processing possessing a variety of useful functionalities, is primarily a mixture of phospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and phospha-tidic acid and contains minor quantities of other water-soluble or hydratable components such as glycolipids and oligosaccharides (78). The degumming of oil with... 

Figure 4.12. (Top ) The binary phase diagram of didodecyl phosphatidylethanolamine -water mixtures. (Adapted from [15].) Single-phase regions are white, two-pha% regions shaded. The thermotropic behaviour at about 20% w/w water is illustrated by die line ABC. (Bottom ) The trajectory of the line ABC in the local/global domain (see previous figure), showing the variation of molecular shape as a function of temperature for this l d. The phase diagram can be reconciled with the local/global behaviour if the "lamellar" (L) phase is in fact a mesh structure, i.e. porous lamellae.

The implications of the existence of an enormous diversity of lipid species and fatty acid patterns in different membranes within one organism as well as the variations between different organisms have posed a allenge for a long time. Any model of lipid bilayer function has to take account of these variations. If we consider erythrocyte membrane phospholipids for example, the rat has about 50% phosphatidylcholine (PC) and only about 10% sphingomyelin (SM), whereas the sheep erythrocyte membrane contains more than 50% SM and no PC. By contrast the total membrane content of phosphatidylethanolamine (PE) + PC + PM in mammalian species is fairly constant, equal to about 15-20%, and the rest are charged lipids... 

Fig. 7. The increase in surface pressure of phospholipid monolayers as a function of signal-peptide concentration for the various E. coli LamB synthetic signal sequences (from Briggs, 1986). A monolayer of egg phosphatidylethanolamine and egg phosphatidylgly-cerol (65 35) was spread from a benzene solution onto 5 mM Tris buffer, pH 7.3, yielding a hnal surface pressure of 20 dyn/cm after evaporation of the benzene. The peptide was added by injecting a concentrated solution below the lipid-water interface. The surface pressure was measured by the du Noiiy ring method with a Fisher Autotensiomat equipped with a platinum-iridium ring. The plateau values are plotted as a function of the peptide concentration for the wild-type (O), Pro— Leu pseudorevertant (A), and deletion-mutant ( ) peptides.

Hunter GW, Negash S, Squier TC. Phosphatidylethanolamine modulates Ca-ATPase function and dynamics. Biochemistry 1999 38 1356-1364. 

Docosahexaenoic acid (DHA, 22 6n-3) is the most abundant polyunsaturated fatty acid (PUFA) acylated to the aminophospholipids phosphatidylethanolamine (PE) and phosphatidylserine (PS) in membranes of neurons within the central nervous system (CNS) (Naughton, 1981 Salem et al., 1986). It can occur in concentrations exceeding 30-mol% of the fatty acids (Salem, 1989). The high enrichment ofDHA in synaptosomes is especially striking and suggests that DHA has unique properties that are required for optimal neuronal function. This concentration in the CNS is even more remarkable when one considers that sources of n-3 fatty acids are disproportionately limited in the terrestrial food chain compared to the much more abundant n-6 fatty acids. 

In our previous reports, we have shown that infant rhesus monkeys born from mothers fed an n-3 fatty acid-deficient diet and then also fed a deficient diet after birth developed low levels of n-3 fatty acids in the brain and retina and impairment in visual function (Neuringer et al., 1984, Connor et al., 1984, Neuringer et al., 1986). The specific biochemical markers of the n-3-deficient state were a marked decline in the DHA of the cerebral cortex and a compensatory increase in n-6 fatty acids, especially docosapenta-enoic acid (22 5n-6). Thus, the sum total of the n-3 and n-6 fatty acids remained similar, about 50% of the fatty acids in phosphatidylethanolamine and phosphatidylserine, indicating the existence of mechanisms in the brain to conserve polyunsaturation of membrane phospholipids as much as possible despite the n-3-deficient state. 

Because altered sodium channels have been implicated in kdr and kdr-like resistance phenomena in insects, basic research on the biochemistry and molecular biology of this molecule, which plays a central role in normal processes of nervous excitation in animals, is of immediate relevance. The results of recent investigations of the voltage-sensitive sodium channels of vertebrate nerves and muscles have provided unprecedented insight into the structure of this large and complex membrane macromolecule. Sodium channel components from electric eel electroplax, mammalian brain, and mammalian skeletal muscle have been solubilized and purified (for a recent review, see Ref. 19). A large a subunit (ca. 2 60 kDa) is a common feature of all purified channels in addition, there is evidence for two smaller subunits ( Jl and J2 37-39 kDa) associated with the mammalian brain sodium channel and for one or two smaller subunits of similar size associated with muscle sodium channels. Reconstitution experiments with rat brain channel components show that incorporation of the a and pi subunits into phospholipid membranes in the presence of brain lipids or brain phosphatidylethanolamine is sufficient to produce all of the functional properties of sodium channels in native membranes (AA). Similar results have been obtained with purified rabbit muscle (45) and eel electroplax (AS.) sodium channels. 

Fig. 4. In-sample temperature change with elapsed time after the commencement of heating hydrated phosphatidylethanolamine (a, b) and water (c) samples contained in 1 mm diameter capillaries using a temperature-regulated coaxial air stream. The thermal lag in (a) and (b) is due to the diversion of heat away from raising sample temperature and into chain melting which accounts for most of the enthalpy of the transition at 66 °C. T-jumps were from 30 °C to 92 °C (a, c) and 125 °C (b). The inset shows the calculated temperature profile across the capillary diameter in (a) as a function of time in seconds following the T-jump. Adapted from Ref. [31]...

The two layers of the phospholipid bilayer membrane are not identical in composition. For instance, in human red blood cells, approximately 80% of the phospholipids in the outer layer of the membrane are phosphatidylcholine and sphingomyelin whereas phosphatidylethanolamine and phosphatidylserine make up approximately 80% of the inner layer. In addition, carbohydrate groups are found attached only to those phospholipids found on the outer layer of a membrane. Here they participate in receptor and recognition functions. 

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