Mediated transport, concepts

Out of this concept grew the cardinal idea of carrier mediated transport. Necessary for this was the development of a more coherent theoretical analysis built upon the general notion of facilitated diffusion. The major insight here came from Widdas who proposed in 1952 that carrier mediated transport would explain earlier data such as the transport of glucose across the sheep placenta, as well as his own observations on glucose entry into the erythrocyte. There were three assumptions made in developing this quantitative hypothesis ... 

The penetration of water-soluble material into the cell is thought to occur via a hypothetical membrane-transport "carrier," since a significant part of the cell membrane is composed of lipids and is therefore somewhat restrictive to the passive diffusion of metabolically important substances in aqueous solution. The lattice-pore model has been proposed by Naftalin (1972) as an alternative to the carrier model for sugar transport in erythrocyte membranes. However, the concept of carrier-mediated transport has been postulated by many investigators, with the general scheme consisting of three steps (1) binding of the penetrant to the "carrier" site (2) translocation of the penetrant across the membrane and (3) release of the penetrant on the other side of the membrane. 

Figure 15.1 Schematic illustration of the extended phase concept during drug elimination in the kidney and liver. Phase 0 = uptake of drugs from the blood into the hepatocytes or proximal tubule epithelial cells. This uptake is mediated by transport proteins belonging to the SLC (solute carrier) transporter superfamily. Phase I and...

A plot of rate of transport against solute concentration in the tubule (Figure 8.3) shows fm, the tubular transport maximum to be analogous with Vmax for an enzyme, which is a maximum rate of solute transport across tubular cells. Assuming a fixed GFR, the point at which the plotted line begins to deviate from linearity, indicates that the substance exceeds a critical threshold concentration and begins to be excreted in the urine. When the plotted line reaches a plateau indicating that saturation point, that is tm has been reached, the rate of excretion is linear with increase in plasma concentration. The concept of fm as described here for tubular reabsorption applies equally well to carrier-mediated secretory processes. If the fm value for a particular is exceeded for any reason, there will be excretion of that solute in the urine. 

In other cases, however, and in particular when sublattices are occupied by rather immobile components, the point defect concentrations may not be in local equilibrium during transport and reaction. For example, in ternary oxide solutions, component transport (at high temperatures) occurs almost exclusively in the cation sublattices. It is mediated by the predominant point defects, which are cation vacancies. The nearly perfect oxygen sublattice, by contrast, serves as a rigid matrix. These oxides can thus be regarded as models for closed or partially closed systems. These characteristic features make an AO-BO (or rather A, O-B, a 0) interdiffusion experiment a critical test for possible deviations from local point defect equilibrium. We therefore develop the concept and quantitative analysis using this inhomogeneous model solid solution. 

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