Biological membranes cation transport

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. 

Some 20 years ago it was observed that certain antibiotics could induce the movement of aqueous K+ ions into the mitochondria of cells, but not that of aqueous Na+ ions. These antibiotics, many of which are naturally occurring, are termed ionophores, i.e. neutral molecules which can mediate the transport of the essential groups IA and IIA cations across biological membranes.76 The essential features of an ionophore are a highly polar interior, a hydrophobic exterior and conformational flexibility. Many are cyclic peptides, the coordination properties of the cyclic molecules are considerably different to those of the linear peptides. These differences are outlined in Chapter 20.2. 

Biological membranes present a barrier to the free transport of cations, as the hydrophilic, hydrated cations cannot cross the central hydrophobic region of the membrane which is formed by the hydrocarbon tails of the lipids in the bilayer. Specific mechanisms thus have to be provided for the transport of cations, which therefore allow for the introduction of controls. Such translocation processes may involve the active transport of cations against the concentration gradient with expenditure of energy via the hydrolysis of ATP. These ion pumps involve enzyme activity. Alternatively, facilitated diffusion may occur in which the cation is assisted to cross the hydrophobic barrier. Such diffusion will follow the concentration gradient until concentrations either side of... 

In order to be able to distinguish between active and passive transport through biological membranes, P. Meares and H. H. Ussing (95) likewise made a study of the fluxes through a membrane under the influence of diffusion together with an electric current. They studied the influxes and the outfluxes of sodium- and chloride ions at a cation exchange resin membrane. They started from the Nemst-Planck flux equations of the type ... 

Ionophores (ion carriers) are lipophilic substances, capable of binding and carrying specific cations through the biological membranes. They differ from the uncouplers in that they promote the transport of cations other than H+ through the membrane. 

It has been generally assumed that iron is transported across biological membranes in the ferrous form and that ferric iron would have to be reduced before it can be used by the organism. Thus, based on nutritional studies it has long been recognized that Fe(II) is1 more effectively absorbed than Fe(III), and this has been attributed to differences in the thermodynamic and kinetic stability of the complexes and chelates formed by these cations (for review, see Ref. 2). The experimental proof of a transport in the ferrous form has, however, not been given until quite recently in studies of iron transport in isolated mitochondria (23) as well as in enterobacteria (33). In rat liver mitochondria we have found that Fe(III) donated from a metabolically inert water soluble complex of sucrose interacts with the respiratory chain at the level of cytochrome c (and possibly cytochrome a) (23, 32) (Figure 1 B), which has a oxidation-reduction potential of around +250 mV (34) and is localized to the outer phase of the mitochondrial inner membrane (35). 

Zhou, M., Xia, L. and Wang, J. (2007) Metformin transport by a newly cloned proton-stimulated organic cation transporter (plasma membrane monoamine transporter) expressed in human intestine. Drug Metabolism and Disposition The Biological Fate of Chemicals, 35 (10), 1956—1962. 

Structure of gramicidin A (a) and the formation of a helical pore through a lipid bilayer by assembly of two gramicidin A molecules via their formyl groups at the N termini (b). A variety of monovalent cations are transported through the static pore. [Structure (b) is reproduced with permission from Y.A. Ovchinnikov Physico-chemical basis of ion transport through biological membranes lonophores and ion channels. Eur. J. Biochem. 94,321 (1979).]... 

Many substances cross biological membranes according to their lipid solubility. Other polar molecules, such as amino acids and glucose, cross the membranes more rapidly than expected according to their solubUity in lipids. Cations, such as Na" and K, also cross membranes rapidly in spite of their hydrophilic nature. This passive transport of substances at higher rates than predicted from their lipid solubility is termed facilitated diffusion. That proteins are directly involved in facilitated diffusion was shown by comparison of experiments with natural membranes and synthetic membranes produced with phospholipid films. With phospholipid films all molecules, except water, diffuse according to lipid solubility and molecular size. Ions are essentially impermeable. The addition of membrane proteins, however, frequently allowed many polar and charged species to penetrate the membrane at rates comparable to natural membranes. 

Ibere are relatively few physical techniques available for the characterization of the interaction of monovalent cations with biological molecules responsible for cation transport. However, nuclear magnetic resonance (NMR) spectroscopy has proven to be a very powerful technique for the study of the transport process and the molecular systems responsible for the transport. NMR techniques can be used to determine the three-dimensional structure of the channel, to determine the thermodynamic parameters for the incorporation of the transport system into the membrane environment, to obtain the thermodynamic parameters for the binding of the cations to the channel, to determine the kinetic activation enthalpy for the transport process, and to study the internal motion of the peptide or protein that forms the channel. 

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