Cell membrane Valinomycin

This review addresses the issues of the chemical and physical processes whereby inorganic anions and cations are selectively retained by or passed through cell membranes. The channel and carrier mechanisms of membranes permeation are treated by means of model systems. The models are the planar lipid bilayer for the cell membrane, Gramicidin for the channel mechanism, and Valinomycin for the carrier mechanism. 

The transport of K+ ions through cell membranes by antibiotics (valinomycin) has been a very important example. Addition of K+ ions to the subphase of a valinomycin monolayer showed that the surface potential became positive. This clearly indicates the ion-specific binding of K+ to valinomycin (Birdi, 1989). 

Alkali metal transport in biochemistry is a vital process in maintenance of cell membrane potentials of use, for example, in nerve signal transduction and is at the core of some of the early work on artificial ionophores that mimic natural ion carriers such as valinomycin. Ionophore mediated ion transport is much slower than transport through cation and anion ion channel proteins, however. 

This Na+/K+ selectivity is of paramount importance since many physiological functions depend upon its maintenance. The selective transport of K+ across cell membranes is achieved by the natmal antibiotic valinomycin (10), which contains a crownlike cycle of ether oxygens, but also a number of amide linkages. The cycle would seem too large to bind K+... 

How ionophotes like the antibiotic valinomycin transport ions across a cell membrane (Section 3.7B)... 

The antibiotics valinomycin and gramicidin A operate by acting, within the cell membrane as ion carriers and ion channels respectively (see Chapter 10). 

The peptides valinomycin (Fig. 10.64) and gramicidin A (Fig. 10.67) both act as ion conducting antibiotics and allow the uncontrolled movement of ions across the cell membrane. Unfortunately, both these agents show no selective toxicity for bacterial over mammalian cells and are therefore useless as therapeutic agents. Their mechanism of action is interesting nevertheless. 

Valinomycin acts as an ion carrier and in some ways could be looked upon as an inverted detergent. Since it is cyclic, it forms a doughnut-type structure where the polar carbonyl oxygens of the ester and amide groups face inside, while the hydro-phobic side-chains of the valine and hydroxyisovalerate units point outwards. This is clearly favoured since the hydrophobic side-chains can interact via van der Waals forces with the fatty Upid interior of the cell membrane, while the polar hydrophilic... 

A group of antibiotics (e.g., valinomycin, nigericin, and gramicidin A) transport cations across the cell membrane. Such agents, known as ionophores, are widely used to probe membrane structure and function. Ionophores uncouple oxidative phosphorylation. Valinomycin, a cyclic peptide (Figure 14-17), forms a lipid-soluble complex with K+ that readily passes through the inner membrane, whereas K+ by itself does not. In the valinomycin-K complex, hydrophobic groups, present on the outside, facilitate transport of the complex in the lipid environment ... 

The purpose of the reference barrel is to allow for the simultaneous measurement of the cell membrane potential while measuring the intracellular ion activities with the ISE portion of the device. Tims, in practice, a second single-barrel reference micropipet electrode is placed in the bathing solution outside the cell so that the potential between the two KCl-filled electrodes can always be monitored to obtain the instantaneous cell membrane potential (E ). The potential of the liquid membrane ISE barrel can also be monitored versus the external reference electrode. In this manner, potential changes due to variations in the cell membrane potential can be taken into account when calculating the intracellular ion activities. Alternatively, only the potential difference between both barrels of the electrode could be monitored. This potential should only be dependent on the intracellular activity of the analyte ion (not affected by the cell membrane potential). For certain ion measurements, e.g., K using a valinomycin based liquid micropipet electrode, leakage of K+ from the reference barrel could present a problem. In such cases, the reference barrel and the outer reference pipet should be filled with a solution other than 3 M KCl. 

In biochemistry and medicine, the membrane active ligands have been valuable tools for studying ion transport and related cell membrane phenomena. Valinomycin has been most widely used and has been applied to a variety of biological systems. For... 

There are several antibiotics called ionophores. Some notable examples are monensin, nonactin, gramicidin, and valinomycin. The structures of monensin and nonactin are shown below, lonophore antibiotics like monensin and nonactin coordinate with metal cations in a manner similar to crown ethers. Their mode of action has to do with disrupting the natural gradient of ions on each side of the cell membrane. 

Figure 15-6b shows how the electrode works. The key in this example is the ligand, L (called an ionopkore), which is soluble inside the membrane and selectively binds analyte ion. In a potassium ion-selective electrode, for example, L could be valinomycin, a natural antibiotic secreted by certain microorganisms to carry ion across cell membranes. The ligand L is chosen to have a high affinity for analyte cation and low affinity for other ions. 

Figure 2.22 The biological receptors valinomycin (2.106) and monesin (2.107) which are able to transport cations across cell membranes.

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