Monensin sodium transport

Sodium permeabilities were found to be 62, 82, 126 and 158 ni /sec for 15, 22.5, 30 and 37.5 yM monensin respectively and lithium permeabilities were 12 uid 33 ni /sec for 400 and 800 yM monensin respectively. Thus, the permeabilities extrapolated to 1 yM of monensin for Ihe same don and lipid concentration are for Na 4.0 0.4 m /sec, for Li 0.035 4 0.005 nn sec. These results show that within the concentration range studied the sodium transport rate increases fairly linearly with the ionophore concentration, indicating that the dominant transporting species is a 1 1 complex of the sodium ionophore. The much higher value obtained for sodium either indicates that the complex association-dissociation processes determine the overall rate of transport or reflects the difference in the binding constants for these two ions. 

The answer h3[IVA 2], Monensin, an ionophore, causes acute cardiac effects by interring with calcium and sodium transport Elevated intracellular calcium levels impair mitochondrial respiration, resulting in significant myocardial necrosis. The damaged myocardium is repaired by fibrosis ich lea to cardiac muscle insufficiency, exercise intolerance, and sometimes sudden death in survivors of acute rtxuiensin toxicosis. 

Individual polyethers exhibit varying specificities for cations. Some polyethers have found appHcation as components in ion-selective electrodes for use in clinical medicine or in laboratory studies involving transport studies or measurement of transmembrane electrical potential (4). The methyl ester of monensin [28636-21 -7] i2ls been incorporated into a membrane sHde assembly used for the assay of semm sodium (see Biosensors) (5). Studies directed toward the design of a lithium selective electrode resulted in the synthesis of a derivative of monensin lactone that is highly specific for lithium (6). 

Cholanic acid also possesses the ability of transporting cations across a lipophilic membrane but the selectivity is not observed because it contains no recognition sites for specific cations. In the basic region, monensin forms a lipophilic complex with Na+, which is the counter ion of the carboxylate, by taking a pseudo-cyclic structure based on the effective coordination of the polyether moiety. The lipophilic complex taken up in the liquid membrane is transferred to the active region by diffusion. In the acidic region, the sodium cation is released by the neutralization reaction. The cycle is completed by the reverse transport of the free carboxylic ionophore. 

Organic molecules forming complexes with sodium ions in water, such as monensin, speed up ion transport by factors of about 10, molecules that form tunnels by factors of 10 ° and more. Scheme 2.7.1 depicts two typical structures of ion transport agents, namely monensin and filipin. Gramicidine, on the other hand, is thought to form a pore in membranes. The only clear-cut distinction between an ion pore and an ion transporter is that a pore can be closed and reopened by stopper molecules, whereas ion transport will always occur as long as complexation in membranes and decomplexation in water can occur. 

Monensin (14.12), isolated from Streptomyces cinnamonensis, is a fully hydrogenated pyranyl-furyl-furyl-dioxaspirodecyl derivative of butyric acid, mol. wt. 670 (Lutz, Winkler and Dunitz, 1971). The sodium salt is more soluble in hydrocarbons than in water. It is used to promote growth of cattle, acting by changing active transport in anaerobic rumen bacteria, which favours survival of strains which produce nutritive aliphatic acids. It is also used to treat coccidiosis in chicks. For another example, see gramicidin D (p. 605). 

The structure of the sodium salt of monensin is depicted in Figure 16.3b, where it can be seen that four ether oxygens and two hydroxyl groups surround a sodium ion. The alkyl groups are oriented toward the outside of the complex, and the polar oxygens and the metal ion are on the inside. The hydrocarbon-like surface of the complex permits it to carry its sodium ion through the hydrocarbon-like interior of a cell membrane. This disrupts the normal balance of sodium ions within the cell and interferes with important processes of cellular respiration. Small amounts of monensin are added to animal feed to kill parasites that live in the intestines of chickens, cows, etc. Compounds such as monensin and the crown ethers that affect metal ion transport are referred to as ionophores ( ion carriers ). 

Monensin (Figure 16.6) is a conformationally flexible acyclic polyether that can form complexes with sodium ions. The complex transports sodium ions into cells. The increase in the concentration of sodium ions within the cells structure increases the osmotic pressure. Witer follows the sodium and the consequent cell membrane rupture kills the cell. Farmers add monensin to poultry feed to kill intestinal parasites. 

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