Lipid membranes localization

Kauss, H., Swanson, A.L., Arnold, R., and Odzuck, W. (1969) Biosynthesis of Pectic Substances. Localization of enzymes and products in a lipid-membrane complex. Biochim.Biophys.Acta, 192 55-61. 

Antonenko, Y. N. Bulychev, A. A., Measurements of local pH changes near bilayer lipid membrane by means of a pH microelectrode and a protonophore-dependent membrane potential. Comparison of the methods, Biochim. Biophys. Acta 1070, 279-282 (1991). 

Schreier, S. Frezzatti, W. A., Jr. Araujo, R S. Chaimovich, H. Cuccovia, I. M., Effect of lipid membranes on the apparent pK of the local anesthetic tetracaine Spin label and titration studies, Biochim. Biophys. Acta 769, 231-237 (1984). 

Owing to their chemical structure, carotenes as polyterpenoids are hydrophobic in nature (Britton et al., 2004). Therefore, as it might be expected, the carotenes are bound within the hydrophobic core of the lipid membranes. Polar carotenoids, with the molecules terminated on one or two sides with the oxygen-bearing substitutes, also bind to the lipid bilayer in such a way that the chromophore, constituted by the polyene backbone is embedded in the hydrophobic core of the membrane. There are several lines of evidence for such a localization of carotenoids with respect to the lipid bilayers. 

It is possible, however, that the electrochromic response of some styrylpyridi-nium probes, for example, RH421 (see Fig. 2), is enhanced by a reorientation of the dye molecule as a whole within the membrane. There is a steep gradient in polarity on going from the aqueous environment across the lipid headgroup region and into the hydrocarbon interior of a lipid membrane. Therefore, any small reorientation of a probe within the membrane is likely to lead to a change in its local polarity and hence a solvatochromic shift of its fluorescence excitation spectrum. Such a... 

Other systems like electroporation have no lipids that might help in membrane sealing or fusion for direct transfer of the nucleic acid across membranes they have to generate transient pores, a process where efficiency is usually directly correlated with membrane destruction and cytotoxicity. Alternatively, like for the majority of polymer-based polyplexes, cellular uptake proceeds by clathrin- or caveolin-dependent and related endocytic pathways [152-156]. The polyplexes end up inside endosomes, and the membrane disruption happens in intracellular vesicles. It is noteworthy that several observed uptake processes may not be functional in delivery of bioactive material. Subsequent intracellular obstacles may render a specific pathway into a dead end [151, 154, 156]. With time, endosomal vesicles become slightly acidic (pH 5-6) and finally fuse with and mature into lysosomes. Therefore, polyplexes have to escape into the cytosol to avoid the nucleic acid-degrading lysosomal environment, and to deliver the therapeutic nucleic acid to the active site. Either the carrier polymer or a conjugated endosomolytic domain has to mediate this process [157], which involves local lipid membrane perturbation. Such a lipid membrane interaction could be a toxic event if occurring at the cell surface or mitochondrial membrane. Thus, polymers that show an endosome-specific membrane activity are favorable. 

Local anesthetic activity is also shown by uncharged substances, suggesting a binding site in apolar regions of the channel protein or the surrounding lipid membrane. 

Depending on the pllipid membrane-permeable form of the local anesthetic (p. 26), which must take on its cationic amphiphilic form in order to exert its action (p.204). 

As discussed for N-myristoylation and S-prenylation, even S-acylation of proteins with a fatty acid which in the vast majority of cases is the C16 0 palmitic acid, plays a fundamental role in the cellular signal-transduction process (Table l). 2-5 14 While N-myristoylation and S-prenylation are permanent protein modifications due to the amide- and sulfide-type linkage, the thioester bond between palmitic acid and the peptide chain is rather labile and palmi-toylation is referred to as a dynamic modification. 64 This reversibility plays a crucial role in the modulation of protein functions since the presence or absence of a palmitoyl chain can determine the membrane localization of the protein and can also be used to regulate the interactions of these proteins with other proteins. Furthermore, a unique consensus sequence for protein palmitoylation has not been found, in contrast to the strict consensus sequences required for N-myristoylation and S-prenylation. Palmitoylation can occur at N- or C-terminal parts of the polypeptide chain depending on the protein family and often coexists with other types of lipidation (see Section 6.4.1.4). Given the diversity of protein sequences... 

The local anesthetics are converted in the liver (amide type) or in plasma (ester type) to more water-soluble metabolites, which are excreted in the urine. Since local anesthetics in the uncharged form diffuse readily through lipid membranes, little or no urinary excretion of the neutral form occurs. Acidification of urine promotes ionization of the tertiary amine base to the more water-soluble charged form, leading to more rapid elimination. 

Bebawy et al. [186] demonstrated that CPZ (9) and vinblastine inhibited each other s transport in a human lymphoblastic leukemia cell line (CCRF-CEM/VLBioo). CPZ (9) reversed resistance to vinblastine but not to fluores-cently labeled colchicine and it increased resistance to colchicine. Colchicine was supposed to be transported from the inner leaflet of the membrane and vinblastine from the outer leaflet. CPZ (9) was assumed to be located in the inner membrane leaflet where it interacts with anionic groups of phospholipids and it may inhibit vinblastine transport via allosteric interactions. The authors concluded that transport of P-gp substrates and its modulation by CPZ (9) (or verapamil (79)) are dependent on substrate localization inside the membrane. Contrary to CPZ (9) location in the inner leaflet of the membrane, other modulators and substrates of P-gp were proved to be rather localized within the interface region of the membrane. The location of seven P-gp substrates and two modulators within neutral phospholipid bilayers was examined by NMR spectroscopy by Siarheyeva et al. [129]. The substrates and the modulators of P-gp were found in the highest concentrations within the membrane interface region. The role of drug-lipid membrane interactions in MDR and its reversal was reviewed in detail elsewhere [53,187]. 

Cadas, H., Schinelli, S., and Piomelli, D. (1996b). Membrane localization ofTV-acylphosphatidyletha-nolamine in central neurons Studies with exogenous phospholipases. J. Lipid Mediat. Cell Signal 14, 63-70. 

Stretch-activated proteins in animal cell membranes that are candidates for osmosensing activity include mechanosensitive ion channels and the membrane-localized enzyme phospholipase A2 (PLA2). The former proteins remain to be conclusively linked to osmosensing. Activity of PLA2 is sensitive to packing of the lipid bilayer of the cell and is responsive to osmotic changes, two attributes that mark it as a prime candidate for a stretch-activated sensor (Lehtonen and Kinnunen, 1995). 

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