Transport systems/transporters facilitated diffusion

The resorption process is facilitated by the large inner surface of the intestine, with its brush-border cells. Lipophilic molecules penetrate the plasma membrane of the mucosal cells by simple diffusion, whereas polar molecules require transporters (facilitated diffusion see p. 218). In many cases, carrier-mediated cotransport with Na"" ions can be observed. In this case, the difference in the concentration of the sodium ions (high in the intestinal lumen and low in the mucosal cells) drives the import of nutrients against a concentration gradient (secondary active transport see p. 220). Failure of carrier systems in the gastrointestinal tract can result in diseases. 

For the absorption of carbohydrates, amino acids, and peptides, a variety of transport systems following facilitated diffusion and active mechanisms have been identified on a molecular and functional level. D-Glucose is mainly absorbed via the Na -dependent transporter SGLTl in the brush-border membrane of enterocytes [18-20]. It is transported across the basolateral membrane by facilitated diffusion via the hexose transporter GLUT-2. Besides SGLTl, the Na +-independent transport protein GLUT-5 is localized in the apical enterocyte membrane, recognizing fructose as a substrate [21]. 

Calcium is absorbed from the intestine by facilitated diffusion and active transport. In the former, Ca " moves from the mucosal to the serosal compartments along a concentration gradient. The active transport system requires a cation pump. In both processes, a calcium-binding protein (CaBP) is thought to be required for the transport. Synthesis of CaBP is activated by 1,25-DHCC. In the active transport, release of Ca " from the mucosal cell into... 

In addition to the passive diffusional processes over lipid membranes or between cells, substances can be transferred through the lipid phase of biological membranes through specialized systems, i.e., active transport and facilitated diffusion. Until recently, the active transport component has been discussed only for nutrients or endogenous substances (e.g., amino acids, sugars, bile acids, small peptides), and seemed not to play any major role in the absorption of pharmaceuticals. However, sufficient evidence has now been gathered to recognize the involvement of transporters in the disposition of pharmaceuticals in the body [50, 127]. 

Carrier-mediated passage of a molecular entity across a membrane (or other barrier). Facilitated transport follows saturation kinetics ie, the rate of transport at elevated concentrations of the transportable substrate reaches a maximum that reflects the concentration of carriers/transporters. In this respect, the kinetics resemble the Michaelis-Menten behavior of enzyme-catalyzed reactions. Facilitated diffusion systems are often stereo-specific, and they are subject to competitive inhibition. Facilitated transport systems are also distinguished from active transport systems which work against a concentration barrier and require a source of free energy. Simple diffusion often occurs in parallel to facilitated diffusion, and one must correct facilitated transport for the basal rate. This is usually evident when a plot of transport rate versus substrate concentration reaches a limiting nonzero rate at saturating substrate While the term passive transport has been used synonymously with facilitated transport, others have suggested that this term may be confused with or mistaken for simple diffusion. See Membrane Transport Kinetics... 

There are, however, various types of active transport systems, involving protein carriers and known as uniports, symports, and antiports as indicated in Figure 3.7. Thus, symports and antiports involve the transport of two different molecules in either the same or a different direction. Uniports are carrier proteins, which actively or passively (see section "Facilitated Diffusion") transport one molecule through the membrane. Active transport requires a source of energy, usually ATP, which is hydrolyzed by the carrier protein, or the cotransport of ions such as Na+ or H+ down their electrochemical gradients. The transport proteins usually seem to traverse the lipid bilayer and appear to function like membrane-bound enzymes. Thus, the protein carrier has a specific binding site for the solute or solutes to be transferred. For example, with the Na+/K+ ATPase antiport, the solute (Na+) binds to the carrier on one side of... 

Glucose cannot diffuse directly into cells, but enters by one of two transport mechanisms a Na+-independent, facilitated diffusion transport system or a Na+-monosaccharide co-transporter system. 

The Permease Systems of Bacteria. The best defined of these is the galactoside permease of E. coli. This transport system mediates the active accumulation of galactosides in the presence of metabolic energy and the facilitated diffusion of these compounds when the energy system is blocked (8). A specific galactoside-binding protein has been implicated, but it seems clear that the system is different from the phosphotransferase system described above since no covalent intermediates of... 

The various proposed components of the permease system are based upon the response of the transport system to genetic or environmental changes. The complex nature postulated for the intact permease system is necessary to account for the various observed phenomena such as facilitated diffusion, active concentration, facilitated efflux, exchange diffusion, and counter transport of one compound driven by the downhill efflux of a second (2). 

Vanadate transport in the erythrocyte was shown to occur via facilitated diffusion in erythrocyte membranes and was inhibited by 4,4 -diisothiocyanostilbene-2,2 -disulfonic acid (DIDS), a specific inhibitor of the band 3 anion transport protein [23], Vanadium is also believed to enter cells as the vanadyl ion, presumably through cationic facilitated diffusion systems. The divalent metal transporter 1 protein (called DMT1, and also known as Nramp2), which carries iron into cells in the gastrointestinal system and out of endosomes in the transferrin cycle [24], has been proposed to also transport the vanadyl cation. In animal systems, specific transport protein systems facilitate the transport of vanadium across membranes into the cell and between cellular compartments, whereas the transport of vanadium through fluids in the organism occurs via binding to proteins that may not be specific to vanadium. 

Chaillou, S., Pouwels, P. FI., and Postma, P. W. 1999. Transport of D-xylose in Lactobacillus pentosus, Lactobacillus casei, and Lactobacillus plantarum evidence for a mechanism of facilitated diffusion via the phosphoenolpyruvatemannose phosphotransferase system. J. Bacteriol., 181, 4768-4113. 

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