Cations, lipid-soluble

Bilayer phase transitions are sensitive to the presence of solutes that interact with lipids, including multivalent cations, lipid-soluble agents, peptides, and proteins. 

Among anticoccidials, polyether antibiotics have been the most widely used in the broiler industry over the last two decades because they provide excellent disease control and are refractory to resistance development (3). Polyether antibiotics are branch chained, polyoxygenated carboxylic acids that act as mobile carriers of cations (4) by rendering cations lipid-soluble, thereby enabling them to pass across membranes. This process disrupts cationic cross-membrane gradients and is responsible for their anticoccidial activity T3J. 

There appear to be two major ways by which ionophores aid ions to cross membrane barriers. Ionophores such as valinomycin and nonactin enclose the cation such that the outside of the complex is quite hydro-phobic (and thus lipid-soluble). The transport behaviour thus involves binding of the cation at the membrane surface by the antibiotic, followed by diffusion of the complexed cation across the membrane to the opposite surface where it is released. Such carrier type ionophores can be very efficient, with one molecule facilitating the passage of thousands of ions per second. A prerequisite for efficient transport by this type of ionophore is that both the kinetics of complex formation and dissociation be fast. 

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... 

Molecular mechanism of ion transport across membrane Cells are enclosed by a membrane of about 70 A thickness and composed of double layers of protein separated by lipids. Cation cannot pass through the lipid layer without encapsulation and thus the enclosed cation presents an organic, lipid soluble surface to the membrane. 

The improved DPMD" decolorization assay is suitable for water-soluble as well as lipid-soluble antioxidants [33]. A stock solution of DMPD cation radical is diluted to A5i7 5n > =0.7-70.8 and after equilibration at 25°C stabilized with ethanol or an acetate buffer (pH 5.6). The experiment is conducted at 30°C and the absorbance of the reaction mixture is read out after 6 minutes. The measurement values obtained by the method with the cation radical DMPD are comparable with those obtained in the ABTS assay. As the cost of the DPMD is several times lower, it could be successfully used as an alternative for the ABTS assay [33]. 

Glasses exist that fnnction as selective electrodes for many different monovalent and some divalent cations. Alternatively, a hydrophobic membrane can be made semiper-meable if a hydrophobic molecnle called an ionophore that selectively binds an ion is dissolved in it. The selectivity of the membrane is determined by the structnre of the ionophore. Some ionophores are natnral products, such as gramicidin, which is highly specific for K+, whereas others such as crown ethers and cryptands are synthetic. Ions such as, 1, Br, and N03 can be detected using quaternary ammonium cationic surfactants as a lipid-soluble counterion. ISEs are generally sensitive in the 10 to 10 M range, but are not perfectly selective. The most typical membrane material used in ISEs is polyvinyl chloride plasticized with dialkylsebacate or other hydrophobic chemicals. 

C-P-Q is converted to the charge separated diradical state C h-P -Q-. Then an electron is transferred from Q to the lipid-soluble 2,5-diphenylbenzoquinone Qs 133b yielding Qs. In the third step uncharged semiquinone QsH is formed when the latter accepts a proton from the external aqueous solution. The basic function of a proton shuttle is carried out when the semiquinone radical diffuses through the membrane in the fourth step. It is then oxidized to Qs + by the carotenoid radical cation... 

Some local anaesthetics, such as benzocaine, are totally insoluble in water and cannot ionise. Consequently, there is no cation and therefore no Na+ channel block from within the cell. It is suggested that agents, such as benzocaine, which are very lipid-soluble, exert their effect in the phospholipid bilayer of the axon. This is the basis of the membrane expansion theory of local anaesthetic action. It is also possible that they diffuse laterally form the bilayer into the Na+ channel without ever accessing the axoplasm and in effect produce another variety of Na+ channel block. Repetitive depolarisation of a nerve recruits more Na+ channels and maintains them in the open state for a longer period than normal. 

We have actually measured the electrical potential differences in intact purple membrane bacteria, using the distribution of a lipid-soluble cation as an indicator, and found values of up to 100 mV[E. Bakker,H. Rottenberg, and S. R. Caplan, Biochim. Biophys. Acta, 440, 557 (1976)]. These values obviously correspond to enormous potential gradients across the membrane. 

The onset of local anesthesia can be accelerated by the addition of sodium bicarbonate (1-2 mL) to the local anesthetic solution. This maximizes the amount of drug in the more lipid-soluble (unionized) form. Repeated injections of local anesthetics can result in loss of effectiveness (ie, tachyphylaxis) due to extracellular acidosis. Local anesthetics are commonly marketed as hydrochloride salts (pH 4.0-6.0) to maximize aqueous solubility. After injection, the salts are buffered in the tissue to physiologic pH, thereby providing sufficient free base concentration for diffusion through the axonal membrane. However, repeated injections of the local anesthetic can deplete the buffering capacity of the local tissues. The ensuing acidosis increases the extracellular cationic form, which diffuses poorly and results in tachyphylaxis. Tachyphylaxis to local anesthetics is common in areas with a limited buffer capacity (eg, the cerebrospinal fluid). 

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. 

A further group of biologically available chemical species comprises organic compounds of the trace elements, which may be divided into two groups organic complexes of cations, and metal and non-metal alkyls (Table 3). These species are mainly neutral molecules, in contrast to the ionic species identified in Table 2, and are thought to be taken up as a consequence of their lipid-solubility (Florence et al., 1983). 

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... 

Cationic vesicles have been used to accomplish charge separation (Mon-serrat and Gratzel, 1981). The photosensitiser was a water-soluble porphyrin and electron acceptor was a modified, water-soluble viologen. The porphyrin photo-reduced the viologen which in its reduced form is lipid soluble but water insoluble. Consequently, the reduced species enters the vesicle. So effective is the charge separation that multimer formation of the reduced species in the vesicle can be observed. Another method which has been employed is to immobilise donors and acceptors on the surface of latex particles (Frank et al., 1979). 

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