Anions, lipid-soluble

The exit of drugs from the CNS can involve (1) diffusion across the blood-brain barrier in the reverse direction at rates determined by the lipid solubility and degree of ionization of the drug, (2) drainage from the cerebrospinal fluid (CSP) into the dural blood sinuses by flowing through the wide channels of the arachnoid villi, and (2) active transport of certain organic anions and cations from the CSF to blood across the choroid plexuses... 

A great number of ligands, such as the anions of ethylenediamine-NNN N -tetra-acetic acid (EDTA), described in detail by Schwarzen-bach and his school (29, 30), show a pronounced selectivity for alkaline earth and other metal cations (30). Because of the limited lipid solubility of these ligands and their complexes, such compounds are, however, not suited as ion carriers in lipophilic membranes (Fig. 2). The ability... 

Anions of lipid-soluble phenols such as 2,4-dini-trophenol can serve as effective carriers of protons (Chapter 18). However, proteins usually serve as the natural carriers, both of protons and of other ions. A protein is sometimes pictured as rotating to present the solute-binding surface first to one side, then to the other side of a membrane. However, gated pores or channels are probable for most biological transport. 

Since the discovery in 1964 that the antibiotic valinomydn exhibited alkali cation specificity in rat liver mitochondria, a new area of research has developed, based not only on biological systems but also on model systems such as crown ethers.484 The ability of neutral compounds to form lipid-soluble alkali and alkaline earth complexes was observed in 1951. The structure of the corresponding ligand, the anion of the antibiotic nigericin (78), was characterized as its silver salt in 1968.488 486 Silver was used as a heavy atom crystaUographically, since the Ag+ cation had a radius between that of Na+ and K+, which were the two alkali cations with which nigericin was most active. 

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). 

Action on the plasma membrane is the first and most fundamental of the bewildering array of deleterious effects of the cinnamic and benzoic acids. They reduce the transmembrane electrochemical potential with the immediacy and extent of that action depending on the concentration and lipid solubility of the compound.35,37,45,60 Rate of uptake also is concentration and pH-dependent, with transfer into and across the membrane greatest with lower pH conditions and higher external concentrations.60 Phenolic acid-induced depolarization of membranes causes a nonspecific efflux of both anions and cations accompanying the increased cell membrane permeability, and these membrane effects correlate with an inhibition of ion uptake. The phenolic acids suppress absorption of phosphate, potassium, nitrate, and magnesium ions, and overall changes in tissue... 

This technique involves the extraction of the anion of an organic acid as its ion pair with a lipid soluble quaternary ammonium cation (in our case, this... 

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. 

In the bacterial PI-PLC structures, the top of the barrel rim has several hydrophobic residues that are fully exposed to solvent and poorly defined in the crystal structures (implying significant mobility). The active site of PI-PLC is accessible and well-hydrated, and these mobile elements at the top of the barrel offer a different motif for interactions of the protein with phospholipid interfaces. The PI-PLC from B. thuringiensis (nearly identical in sequence to the enzyme from B. cereus whose crystal structure was determined) exhibits the property of interfacial activation, where enhanced activity is observed when the substrate PI is present in an interface compared to monomeric substrate (Lewis et al., 1993). However, other non-substrate lipids such as phosphatidylcholine (PC), phosphatidic acid (PA), and other anionic lipids have an effect on the activity of PI-PLC toward both substrates PI and water-soluble cIP (Zhou et al., 1997). In particular, the presence of PC enhances the catalytic activity of... 

The antifungal activity of a series of salts of 9-aminoacridine and its derivatives was shown to correlate with the length of the carbon chain of the anion. The effect is thought to be related to increased lipid solubility and ion pair formation. ... 

Both hydrogen atoms at the 5 position of barbituric acid must be replaced. This may be b ause if one hydrogen is available at position S, tautomerization to a highly acidic trihydroxypyrimidine (pK 4) can occur. Consequently, the compound is largely in the anionic form at physiological pHs. with little nonionic lipid-soluble compound available to cross the blood-brain barrier. 

Bilirubin is a lipid-soluble metabolite of hemoglobin that is transported through the bloodstream as an albumin complex to the liver where it is esterified for excretion in urine. It plays an important role in the pathology of many diseases. Its Raman spectrum has been difficult to observe because of its sensihvity to photoisomerization and decomposition. However, under condihons of SERS on Ag electrodes this is suppressed allowing potenhal-dependent spectra to be observed in its free form as well as complexed with cyclodextrins and albumin [327]. The band intensities are higher at more posihve potenhals implicahng adsorption of anionic species on the electrode. 

Uncoupling of oxidative phosphorylation by 2,4-dinitrophenol (2,4-DNP). The anionic form of 2,4-DNP is protonated in the intermembrane space, is lipid soluble, and crosses the inner membrane readily. In the matrix, the protonated form dissociates, abolishing the proton gradient established by substrate oxidation. The ionized form of 2,4-DNP is poorly soluble in the membrane lipids and therefore is not easily transported across the membrane (dashed arrow). It is lipophilic and capable of transporting protons from one side of the membrane to the other (a protonophore), thus abolishing the proton gradient. 

Ammonia and simple aliphatic amines were among the first uncouplers reported for photophosphorylation by Krogmann, Jagendorf and Avron and by Good respectively. Ammonia and simple aliphatic amines in their lipid-soluble, unprotonated forms can freely permeate the thylakoid membrane. Once inside, they can take up protons and be converted to the corresponding ammonium ions [Fig. 10 (B)]. To maintain electrical neutrality, the accumulation of ammonium ions results in the influx of anions. The accumulation of ammonium salts inside consequently results in an osmotic influx of water and swelling of the thylakoids. 

Use. A solution of this oil-soluble quaternary ammonium salt in chloroform or ethyl acetate quantitatively extracts polar, anionic lipids such as steroid conjugates from aqueous solution by a process of anion exchange. 

In view of the partially nonpolar properties of the phenylpyruvate and caprylate anions and of the lipid solubility of their protonation products which are in equilibrium with the anions, it is likely that these organic salts not only release extrinsic hydrophilic proteins which are attached to the membranes, but also affect hydrophobic bonding within the membrane structure. Such effects cannot be seen in protein release experiments because apolar proteins remain insoluble. 

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