Active transport membrane resistance

Drug absorption generally occurs either through passive transcellular or paracellu-lar diffusion, active carrier transport, or active efflux mechanisms. Several methods have been developed to aid in the understanding of the absorption of new lead compotmds. The most common ones use an immortalized cell line (e.g., Caco-2, Madin-Darby canine kidney, and the like) to mimic the intestinal epithelium. These in vitro models provide more predictive permeability information than the artificial membrane systems (i.e., PAMPA and permeability assays, described previously) based on the cells ability to promote (active transport) or resist (efflux) transport. Various in vitro methods are listed in the U.S. FDA guidelines. These are acceptable to evaluate the permeability of a drug substance, and includes a monolayer of suitable epithelial cells, and one such epithelial cell line that has been widely used as a model system of intestinal permeability is the Caco-2 cell line. 

In microbes without a permeability barrier, or when the barrier fails, a mechanism must be in place to export metals from the cytoplasm. These active transport systems involve energy-dependent, membrane-bound efflux pumps that can be encoded by either chromosomal- or plasmid-borne genes. Active transport is the most well-studied metal resistance mechanism. Some of these include the ars operon for exporting arsenic from E. coli, the cad system for exporting cadmium from Staphylococcus aureus, and the cop operon for removing excess copper from Enterococcus hiraeP i9A0... 

Some metals can be converted to a less toxic form through enzyme detoxification. The most well-described example of this mechanism is the mercury resistance system, which occurs in S. aureus,43 Bacillus sp.,44 E. coli,45 Streptomyces lividans,46 and Thiobacillus ferrooxidans 47 The mer operon in these bacteria includes two different metal resistance mechanisms.48 MerA employs an enzyme detoxification approach as it encodes a mercury reductase, which converts the divalent mercury cation into elemental mercury 49 Elemental mercury is more stable and less toxic than the divalent cation. Other genes in the operon encode membrane proteins that are involved in the active transport of elemental mercury out of the cell.50 52... 

Cell monolayers grown on permeable culture inserts form confluent mono-layers with barrier properties and can be used for drug absorption experiments. The most well-known cell line for the in vitro determination of intestinal drug permeability is the human colon adenocarcinoma Caco-2 [20, 21], The utility of the Caco-2 cell line is due to its spontaneous differentiation to enterocytes under conventional cell culture conditions upon reaching confluency on a porous membrane to resemble the intestinal epithelium. This cell model displays small intestinal carriers, brush borders, villous cell model, tight junctions, and high resistance [22], Caco-2 cells express active transport systems, brush border enzymes, and phase I and II enzymes [22-24], Permeability models... 

In a PEMFC, the power density and efficiency are limited by three major factors (1) the ohmic overpotential mainly due to the membrane resistance, (2) the activation overpotential due to slow oxygen reduchon reaction at the electrode/membrane interface, and (3) the concentration overpotential due to mass-transport limitations of oxygen to the electrode surfaced Studies of the solubility and concentration of oxygen in different perfluorinated membrane materials show that the oxygen solubility is enhanced in the fluorocarbon (hydrophobic)-rich zones and hence increases with the hydrophobicity of the membrane. The diffusion coefficient is directly related to the water content of the membrane and is thereby enhanced in membranes containing high water content the result indicates that the aqueous phase is predominantly involved in the diffusion pathway. ... 

For many plant cells, / emb is 2 to 20 ohm m2 for the active transport of H+ ions (protons) out across the plasma membrane (Spanswick, 1981). How large is at(I given by Equation 3.21 for such a proton pump The electrical potential difference created by the active transport of 20 nmol m-2 s-1 of H+ out across a typical membrane resistance for H+ of 10 ohm m2 is... 

HCO3- or CO2 could be actively transported across the plasma membrane or perhaps could cross by facilitated diffusion (Chapter 3, Section 3.4C). Facilitated diffusion would act as a low-resistance pathway in parallel with the ordinary diffusion pathway and consequently would reduce the effective resistance of the plasma membrane. Unfortunately, the actual mechanism for CO2 or HCC>3 movement across the plasma membrane of mesophyll cells is not known with certainty, although for diffusion of CO2 is low enough to account for the observed CO2 fluxes. 

Currently, we can only estimate a value of about 100 s mT1 for the resistance to the diffusion of CO2 into chloroplasts and across their stroma (Table 8-4). Measurement of in vivo is also difficult—analysis of available data indicates that it is most likely less than 200 s m-1. Although active transport or facilitated diffusion of CO2 or HCCb- into chloroplasts may lower the effective resistance, the experimental values for are compatible with the diffusion of CO2 across the chloroplast-limiting membranes. All of the resistances that we have just discussed and their corresponding conductances are summarized in Table 8-4. 

Streptomycin appeared to enter Pseudomonas aeruginosa via active transport.59 In resistant Pseudomonas aeruginosa K102, reduced membrane permeability as well as decreased affinity of streptamine to the ribosome were plasmid-mediated.60 A 3"-deoxystreptomycin, active in vitro against streptomycin-resistant bacteria, was synthesized.61... 

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