Lipid membranes anionic

FIGURE 6-15 Schematic representation of the ion permeability modulation for cation-responsive voltammetric sensors based on negatively charged lipid membranes. Complexation of the guest cation to the phospholipid receptors causes an increase of the permeability for the anionic marker ion. (Reproduced with permission from reference 49.)... 

Lipophilicity. The gross lipophilicity of the ligand and of its complexes plays a very important role whenever substances soluble in organic media of low polarity are needed. This is the case in studies of anion activation and of cation transport through lipid membranes, where salts have to be dissolved in organic phases. The lipophilic character may be controlled via the nature of the hydrocarbon residues forming the ligand framework or attached to it. 

Competition between mono- and di-valent cations has an important role in biological processes. Furthermore, the lipophilicity of a ligand and its complex plays an important role in deciding whether a species is soluble in organic media of low polarity. This has important consequences in areas such as phase-transfer catalysis, the use of crown ethers as anion activators, and in cation transport through lipid membranes. Many crown ethers have now been synthesized with incorporation of long alkyl side chains and enhanced lipophilicity and used successfully in the above areas. 

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]. 

Despite the presence of a large concentration of carbon dioxide in the blood (ca. 1 him), it has been reported that peroxynitrite can diffuse across the red-blood-cell membrane and react with oxyHb [24]. The anionic form (ONOO-) crosses the erythrocyte membrane by using the anion channel band 3 whereas peroxynitrous acid crosses the lipid membranes by rapid passive diffusion [24]. 

The results in Figure 3, obtained with membrane vesicles, show that imposition of a membrane potential difference (inside negative) greatly enhanced the peak uptake of a solute taken up by a Na+-dependent route. The potential difference could be increased by using lipid soluble anions or valinomycin in vesicles with Kf KJ (Colombini and Johnstone, 1974 Murer and Hopfer, 1974 Sigrist-Nelson et al., 1975 Lever, 1977 Hammerman and Sacktor, 1978 Hopfer, 1978 Wright et al 1983 Kimmich etal., 1991). 

The lung also possesses nonenzymatic antioxidants such as vitamin E, beta-carotene, vitamin C, and uric acid. Vitamin E is lipid-soluble and partitions into lipid membranes, where it is positioned optimally for maximal antioxidant effectiveness. Vitamin E converts superoxide anion, hydroxyl radical, and lipid peroxyl radicals to less reactive oxygen metabolites. Beta-carotene also accumulates in cell membranes and is a metabolic precursor to vitamin A. Furthermore, it can scavenge superoxide anion and react directly with peroxyl-free radicals, thereby serving as an additional lipid-soluble antioxidant. Vitamin C is widely available in both extracellular and intracellular spaces where it can participate in redox reactions. Vitamin C can directly scavenge superoxide and hydroxyl radical. Uric acid formed by the catabolism of purines also has antioxidant properties and primarily scavenges hydroxyl radical and peroxyl radicals from lipid peroxidation. 

J. R. Rydall and P. M. Macdonald, Investigation of anion binding to neutral lipid membranes using 2H NMR, Biochemistry 31 (1992), 1092-1099. 

The dependency of the rate at which supersaturation is maintained within the vesicles on anion diffusion rates is clearly revealed when anions of different permeabilities are substituted for OH and the corresponding intravesicular precipitation is followed by turbidity measurements (83). In the case of intravesicular AgCl formation, the increase in turbidity with time due to the addition of Cl was much slower than for Ag20 formation, indicating that diffusion of Cl across the lipid membrane was reduced compared with OH. The formation of intravesicular Ag2S, on the other hand, occurred instantaneously after the addition of (NH4)2S due to diffusion of free molecular H2S across the vesicle membrane. 

With bilayer lipid membranes it is not possible to achieve a fully asymmetric arrangement of head groups or chains. There is no apparent reason why all the molecules of two independent layers should only concentrate in one layer. Nevertheless, a little asymmetric distribution is found in vesicles made of lipid mixtures. Cerebroside sulfate, an anionic monoglycosyl ceramide was, for example, added exclusively to the outer surface of a performed DPPC vesicle (see Scheme 2.2) which was quantitized by the metachromatic effect of acridine orange. 

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