Transport channel model

II The Channel Mechanism of Ion Transport The Gramicidin Channel Model 181... 

Ekins S, Swaan PW. Computational models for enzymes, transporters, channels and receptors relevant to ADME/TQX. Rev Comp Chem 2004 20 333-415. 

Ekins S, Swaan PW (2004) Development of computational models for enzymes, transporters, channels, and receptors relevant to ADME/tox. In Lipkowitz KB, Larter R, Cundari TR (eds) Reviews in computational chemistry, vol. 20. Wiley, Hoboken, NJ, chap 6... 

When applying any of these models it is crucial to understand the main transport mechanisms as well as the metabolic route and characterization of the activity of the transporter/enzyme involved. It is well recognized that the activities of carrier-mediated processes in Caco-2 cells are considerably lower than in vivo [20, 42, 48] therefore, it is crucial to extrapolate in vitro cell culture data to the in vivo situation with great care [18, 20, 42, 48], This is especially important when carrier-mediated processes are involved, as evidenced by a recent report which showed significant differences in gene expression levels for transporters, channels and metabolizing enzymes in Caco-2 cells than in human duodenum [48], If an animal model is used, then potential species differences must also be considered [18, 20, 45],... 

In order to see how the electrode thickness might be optimized in order to provide the lowest electrode resistivity, we have developed a theoretical model to describe the charge/discharge processes in porous carbon electrodes. As a first approximation, let us consider an electrode having two sets of cylindrical pores, namely, nanopores (NP) of less than 3 nm in diameter and transport channels (TC) of more than 20 nm in diameter, with each nanopore having an exit to only one TC. ... 

Figure 1. Model presentation of a few nanopore tiers facing a transport channel.

Sean Ekins and Peter Swaan, Development of Computational Models for Enzymes, Transporters, Channels and Receptors Relevant to ADME/Tox. 

The simple water charmel models can explain the ionomer peak and the small-angle upturn in the scattering data of fhe unoriented samples as well as of the oriented films. Interestingly, the helical structure of backbone segments is responsible for fhe sfabilify of fhe long cylindrical charmels. The self-diffusion behavior of wafer and protons in Nation is well described by the water channel model. The existence of parallel wide channels af high wafer uptake favors large hydrodynamic confributions to electro-osmotic water transport and hydraulic permeation. 

As shown in Figure 16b, the 2-D rib models deal with how the existence of a solid rib affects fuel-cell performance. They do not examine the along-the-channel effects discussed above. Instead, the relevant dimensions deal with the physical reality that the gas channeFdiffusion media interfaces are not continuous. Instead, the ribs of the flow-channel plates break them. These 2-D models focus on the cathode side of the fuel-cell sandwich because oxygen and water transport there have a much more significant impact on performance. This is in contrast to the along-the-channel models that show that the underhumidification of and water transport to the anode are more important than those for the cathode. 

The biological clock may be a feedback system involving ions and ion-transport channels. A model has been proposed341 where membranes introduce configurational changes in response to oscillating ion concentrations whose frequency has been set by a series of environmental parameters such as light, temperature, and tides. 

An important observation needs to be made about channel models and, indeed, model systems in general. Chemists can design molecules to have remarkable shapes and sizes. For a model system, however, it is the properties that determine whether the compound is relevant. A compound that looks like it should be a channel is, as Fitzmaurice has put it, only a long thin thing absent a demonstration of efficacy (Fitzmaurice, 2004). There is no rule that demands selectivity for the biologically relevant ions. Indeed, transport of divalent cobalt has been studied. A cobalttransporting channel is not, however, a biological mimic so far as is currently known. 

In the late 1980s, efforts initiated by Fyles in Canada (Carmichael el al., 1989) and by our own group (Nakano et al., 1990) resulted in two different channel models, both of which incorporated crown ethers. Both of these efforts resulted in channels that show significant transport of alkali metal cations through phospholipid bilayers. Both groups (Gokel and Murillo, 1996) have undertaken extensive stmctme-activity studies to characterize their function. 

Using the key word TRANSPORT the model is built from 10 cells and 15 shifts. Flow velocity is defined to 1 m/s by setting -length and -time step to 50. By that, the total length of the channel is 500 m and the total exposure time 500 s. To get the required information in a selected output file, the input definition must look as follows ... 

The earliest example of a non-peptidic channel model was prepared by Tabushi et al.28 It consisted of a P-cyclodextrin, attached to four hydrophobic tails designed to afford a half-channel. The transport of copper and cobalt was assessed in artificial liposomes (kCo(n) = 4.5 x 10 4s-1), the rate being much faster than in the absence of the half-channel. In the same year, Lehn29 reported a solid-state model of a molecular tunnel consisting of stacked macrocyclic polyethers, with K+ ions located alternatively inside and on top of successive macrocycles. 

Tsang, Y.W., C.F. Tsang, I. Neretnieks, and L. Moreno. 1988. Flow and tracer transport in fractured media a variable aperture channel model and its properties. Water Resour. Res. 24 2049-2060. 

Examples showing that metal speciation is important to metal toxicity include arsenic, copper, selenium, and chromium. While ionic copper (Cu2+) and CuClj are highly toxic, Q1CO3 and Cu-EDTA have low toxicity (Morrison et al, 1989). Toxicity tests show that As(III) is about 50 times more toxic than As(VI). Trivalent chromium is much less toxic than hexavalent chromium, probably because Cr(VI) is much smaller and the chemical structure of chromate is similar to sulfate. A special channel already exists in biomembranes for sulfate transport. While modeling metal speciation is not always possible, and redox equilibrium is not achieved in all natural waters, geochemical modeling of equilibrium species distribution remains one of the methods of discerning metal speciation. 

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