Other Transporters

Some transporters such as Na+-dependent dicarboxylate transporter (NADC1), Na+-dependent bicarbonate transporter 2 (SBC2), Na+-dependent bicarbonate transporter HNBC1, several ion transporters, and channels are also expressed in the intestinal tissues [4]. 

1 Tamai, I. [Molecular characterization of intestinal absorption of drugs by carrier-mediated transport mechanisms]. Yakugaku Zasshi 1997, 117, 415-434. 

Human membrane transporter database a Web-accessible relational database for drug transport studies and pharma-cogenomics. AAPS PharmSci. 2000, 2, E20. 

Comparison of human duodenum and Caco-2 gene expression profiles for 12,000 gene sequences tags and correlation with permeability of 26 drugs. Pharm. Res. 2002, 19, 1400-1416. 

5 Tsuji, A. and I. Tamai. Carrier-mediated intestinal transport of drugs. Pharm. Res. 1996, 13, 963-977. 

The pyruvate transporter [201] and the carnitine translocase [202] have both been isolated but not characterized in any detail. The pyruvate transporter and the carnitine translocase, like the phosphate transporter, are inhibited by maleimide derivatives and mercurials, although at higher concentrations of the sulfhydryl reagents. The pyruvate transporter has been isolated in inactive form covalently linked to phenyl maleimide. Identification was based on the correlation of labelling of the protein with inhibition of transport, and by the fact that mercurials prevented the labelling. The molecular weight of the isolated monomeric protein is surprisingly low, approximately 15000. 

Several additional mitochondrial carrier systems have been reconstituted into active form in proteoliposomes, using as starting material a crude neutral detergent mixture of membrane proteins from submitochondrial particles. These include the citrate transporter [203], the dicarboxylate carrier [204], and the carnitine transporters [202]. These reconstitution activities could be used as a basis for further purification and structural studies, but such studies have not yet been reported. 

Prediction of Hepatobiliary Transport of Substrates from In Vitro Data 

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Einstein relationships hold for other transport properties, e.g. the shear viscosity, the bu viscosity and the thermal conductivity. For example, the shear viscosity t] is given by ... 

One alternative approach to the calculation of the diffusion and other transport coefficier is via an appropriate autocorrelation function. For example, the diffusion coefficie... 

Multiple pathways are a major concern since depostion of PIC would have occurred. Specific soil conditions determine attenuation rates of penta PIC leachate. Once penta reaches the water table, other transport and fate processes become important. Penta exists in two forms ionized and non-ionized. The ionized form is soluble in water, while the non-ionized form is not. The ratio of the two forms in water is dependent on the pH of the aquifer. In alkaline environments penta PIC tend to be more soluble and more susceptible to advective transport and biological decay. Half-lives of penta leachate in groundwater have been estimated ranging from 27 days to 58 years. 

The gradients of H, Na, and other cations and anions established by ATPases and other energy sources can be used for secondary active transport of various substrates. The best-understood systems use Na or gradients to transport amino acids and sugars in certain cells. Many of these systems operate as symports, with the ion and the transported amino acid or sugar moving in the same direction (that is, into the cell). In antiport processes, the ion and the other transported species move in opposite directions. (For example, the anion transporter of erythrocytes is an antiport.) Proton symport proteins are used by E. coU and other bacteria to accumulate lactose, arabinose, ribose, and a variety of amino acids. E. coli also possesses Na -symport systems for melibiose as well as for glutamate and other amino acids. 

In this chapter, we have examined coupled transport systems that rely on ATP hydrolysis, on primary gradients of Na or Ff, and on phosphotransferase systems. Suppose you have just discovered an unusual strain of bacteria that transports rhamnose across its plasma membrane. Suggest experiments that would test whether it was linked to any of these other transport systems. 

The sediment surface separates a mixture of solid sediment and interstitial water from the overlying water. Growth of the sediment results from accumulation of solid particles and inclusion of water in the pore space between the particles. The rates of sediment deposition vary from a few millimeters per 1000 years in the pelagic ocean up to centimeters per year in lakes and coastal areas. The resulting flux density of solid particles to the sediment surface is normally in the range 0.006 to 6 kg/m per year (Lerman, 1979). The corresponding flux density of materials dissolved in the trapped water is 10 to 10 kg/m per year. Chemical species may also be transported across the sediment surface by other transport processes. The main processes are (Lerman, 1979) ... 

Importantly, the currently available transporter models only cover a small fraction of all transporters involved in drug disposition. Other than incorporating current stand-alone transporter models into systemic models to directly predict drug pharmacokinetic properties, continued efforts are still needed to investigate other transporters such as MRP, BCRP, NTCP, and OAT, to get a more complete understanding of the drug pharmacokinetic profile. 

Although cytochalasin B normally functions as a reversible inhibitor of glucose transport, upon exposure to ultraviolet light a small proportion of the bound cytochalasin B molecules become covalently linked to the transporter protein [128-130]. Photolabelling is inhibitable by D-glucose and other transported sugars but not by... 

In bacteria, accumulation of substrates against a concentration gradient can occur through two main classes of transport systems (see [30] for a summary). The prototype of the first class of transporters is the /3-galactoside permease of Escherichia coli (see [31]). It is a relatively simple system involving only a single membrane-bound protein. It catalyzes a lactose-H symport. Other transporters... 

The regulation of NCR-sensitive amino acid transporters in Saccharomyces cerevisiae has many points in common with that of catabolic enzymes. Amino acid permeases, as well as some other transporters of nitrogenous nutrients, are integrated into the regulatory circuits, both general and specific, which control catabolic processes. 

Poorly absorbed compounds have been identified as those with a PSA>140Af Considering more compounds, considerable more scatter was found around the sigmoidal curve observed for a smaller set of compounds [74]. This is partly due to the fact that many compounds do not show simple passive diffusion only, but are affected by active carriers, efflux mechanisms involving P-glycoprotein (P-gp) and other transporter proteins, and gut wall metabohsm. These factors also con-... 

Figure 20-48 shows Wijmans s plot [Wijmans et al.,/. Membr. Sci., 109, 135 (1996)] along with regions where different membrane processes operate (Baker, Membrane Technology and Applications, 2d ed., Wiley, 2004, p. 177). For RO and UF applications, Sj , < 1, and c > Cl,. This may cause precipitation, fouling, or product denatura-tion. For gas separation and pervaporation, Sj , >1 and c < ci. MF is not shown since other transport mechanisms besides Brownian diffusion are at work. 

While potential attacks on all modes of transportation are of concern, the Committee on Assessment of Security Technologies for Transportation believes that the U.S. air transportation system continues to have a high priority for counterterrorism resources, both because of its economic importance and because of the intensified public perception of risk following the September 11, 2001, attacks. The air transportation system can also serve as a testbed for the development of defensive technologies and strategies that can subsequently be applied to other transportation modes. 

A number of transport mediators are transport proteins in the absence of an external energy supply, thermal motion leads to their conformational change or rotation so that the transported substance, bound at one side of the membrane, is transferred to the other side of the membrane. This type of mediator has a limited number of sites for binding the transported substance, so that an increase in the concentration of the latter leads to saturation. Here, the transport process is characterized by specificity for a given substance and inhibition by other transportable substances competing for binding sites and also by various inhibitors. When the concentrations of the transported substance are identical on both sides of the membrane,... 

Fluorescence correlation spectroscopy (FCS) measures rates of diffusion, chemical reaction, and other dynamic processes of fluorescent molecules. These rates are deduced from measurements of fluorescence fluctuations that arise as molecules with specific fluorescence properties enter or leave an open sample volume by diffusion, by undergoing a chemical reaction, or by other transport or reaction processes. Studies of unfolded proteins benefit from the fact that FCS can provide information about rates of protein conformational change both by a direct readout from conformation-dependent fluorescence changes and by changes in diffusion coefficient. 

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