Sodium—amino acid carrier system

The most efficient rectal absorption enhancers, which have been studied, include surfactants, bile acids, sodium salicylate (NaSA), medium-chain glycerides (MCG), NaCIO, enamine derivatives, EDTA, and others [45 17]. Transport from the rectal epithelium primarily involves two routes, i.e., the paracellular route and the transcellular route. The paracellular transport mechanism implies that drugs diffuse through a space between epithelial cells. On the other hand, an uptake mechanism which depends on lipophilicity involves a typical transcellular transport route, and active transport for amino acids, carrier-mediated transport for (3-lactam antibiotics and dipeptides, and endocytosis are also involved in the transcellular transport system, but these transporters are unlikely to express in rectum (Figure 8.7). Table 8.3 summarizes the typical absorption enhancers in rectal routes. 

As mentioned above, the original description of System A in the Ehrlich ascites tumor cell was made possible, in part, because the activity was found to be dependent on the extracellular sodium concentration (15). Hence, System A-mediated transport represents a two-substrate reaction which presumably requires the ternary complex, Na -amino acid-carrier. In isolated rat hepatocytes, the dependence of System A... 

Most food absorption takes place in the small intestine. The gastrointestinal tract possesses specialized carrier systems for certain nutrients such as carbohydrates, amino acids, calcium, and sodium. Some xenobiotics use these routes of passage through the cells, while others enter through passive diffusion. 

Exceptions from Lipinski s rule, i.e., molecules of PSA values > 140 A2 are found to be actively absorbed by carrier-mediated transport systems (Wessel et al. 1998), as shown in Fig. 3. IB. As further detailed in Fig. 3.2, the intestinal epithelium expresses a number of such transport systems for amino acids, organic anions and cations, nucleosides, and hexoses. Among these systems are the apical sodium-dependent bile acid transporter (ASBT Annaba et al. 2007), the monocarboxylate transporter (MCT Halestrap and Price 1999), the sodium-D-glucose co-transporter (SFGT1 Kipp et al. 2003), and the nucleotide transporter SPNT1 (Balimane and Sinko 1999). In addition, the expression of a specialized transporter system for small peptides has been found in the intestinal epithelium with the di/tripeptide transporter, PepTl (Tsuji 2002), after previous functional studies by Hu et al. (1989), and the cloning of PepTl... 

Transport of solutes through the LM occurs by either passive transport or by carrier-facilitated transport. Phenol, for example, is soluble in both phases, and treatment of an aqueous phenol solution with an emulsion results in a lowering of the external concentration of phenol as it passively diffuses through the hydrocarbon (HC) layer and into the internal aqueous phase. Equilibrium is reached when the concentrations of phenol in both aqueous solutions are equal (assuming no other conditions are present which would alter the distribution between the aqueous and HC phases). One way to alter this equilibrium is to trap phenol inside with a sodium hydroxide solution. Phenol ionizes at high pH, and the phenolate ion cannot permeate a HC layer trace amounts of phenol have been completely removed from wastewaters by this system (10, 11). This exclusion of charged molecules by the aliphatic hydrocarbon LM layer is desirable in some applications, but to employ LM enzyme reactors and/or separation systems with amino acids, it is necessary to incorporate carriers into the HC phase. 

A system in which transport (active or by facilitated diffusion) takes place only when a complex between substrate (amino acid, sugar, or anion), sodium ion, and carrier is formed. Within the cell, dissociation of substrate and sodium ion from the carrier occurs freely. 

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