Facilitated diffusion, competition

Facilitated diffusion within organisms takes place when carriers or proteins residing within membranes—ion channels, for instance—organize the movement of ions from one location to another. This diffusion type is a kinetic, not thermodynamic, effect in which a for the transfer is lowered and the rate of diffusion is accelerated. Facilitated diffusion channels organize ion movements in both directions, and the process can be inhibited both competitively and noncompetitively. It is known that most cells maintain open channels for K+ most of the time and closed channels for other ions. Potassium-ion-dependent enzymes include NaVK+ ATPases (to be discussed in Section 5.4.1), pyruvate kinases, and dioldehydratases (not to be discussed further). 

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... 

Facilitated diffusion (specific carrier saturable possible competition operates with concentration gradient no energy required)... 

Equation 3.28 describes the competitive binding of solutes to a limited number of specific sites. In other words, active processes involving metabolic energy do not have to be invoked if a solute were to diffuse across a membrane only when bound to a carrier, the expression for the influx could also be Equation 3.28. This passive, energetically downhill entry of a solute mediated by a carrier is termed facilitated diffusion. 

Facilitated diffusion has certain general characteristics. As already mentioned, the net flux is toward a lower chemical potential. (According to the usual definition, active transport is in the energetically uphill direction active transport may use the same carriers as those used for facilitated diffusion.) Facilitated diffusion causes fluxes to be larger than those expected for ordinary diffusion. Furthermore, the transporters can exhibit selectivity (Fig. 3-17) that is, they can be specific for certain molecules solute and not bind closely related ones, similar to the properties of enzymes. In addition, carriers in facilitated diffusion become saturated when the external concentration of the solute transported is raised sufficiently, a behavior consistent with Equation 3.28. Finally, because carriers can exhibit competition, the flux density of a solute entering a cell by facilitated diffusion can be reduced when structurally similar molecules are added to the external solution. Such molecules compete for the same sites on the carriers and thereby reduce the binding and the subsequent transfer of the original solute into the cell. 

Both active and passive fluxes across the cellular membranes can occur simultaneously, but these movements depend on concentrations in different ways (Fig. 3-17). For passive diffusion, the unidirectional component 7jn is proportional to c°, as is indicated by Equation 1.8 for neutral solutes [Jj = Pj(cJ — cj)] and by Equation 3.16 for ions. This proportionality strictly applies only over the range of external concentrations for which the permeability coefficient is essentially independent of concentration, and the membrane potential must not change in the case of charged solutes. Nevertheless, ordinary passive influxes do tend to be proportional to the external concentration, whereas an active influx or the special passive influx known as facilitated diffusion—either of which can be described by a Michaelis-Menten type of formalism—shows saturation effects at higher concentrations. Moreover, facilitated diffusion and active transport exhibit selectivity and competition, whereas ordinary diffusion does not (Fig. 3-17). 

Facilitated diffusion is a simple mechanism proposed to explain transport of water soluble compounds. The main characteristics of this transport system are that membrane permeability exceeds that predicted from partition coefficients, transport occurs down a concentration gradient, transport is saturable, and competition occurs between isomers. Facilitated diffusion has been used to explain cellular uptake of sugars and amino acids. 

Facilitated diffusion is very similar to passive diffusion with the difference that transfer across membranes is assisted by the participation of carrier proteins embedded in the membrane bilayer. Again, the direction of passage will be from the side of the membrane with high concentration of a chemical to the side with low concentration this also occurs without energy expenditure by the cell. Such a process is somewhat specific in the sense that it applies to molecules that are able to bind to a carrier protein. Absorption of nutrients such as glucose and amino acids across the epithelial membrane of the gastrointestinal tract occurs by facilitated diffusion. Since a finite number of carriers are available for transport, the process is saturable at high concentrations of the transported molecules and competition for transport may occur between molecules of similar structure. 

Xylose is taken up in S. cerevisiae by the glucose transporters [108]. These are permeases that transport sugars by facilitated diffusion [109] (Fig. 3), and have about two orders of magnitude lower affinities towards xylose than glucose (Table 2), which leads to competition between glucose and xylose when simultaneously present in the fermentation medium. When these two sugars were cofermented by recombinant S. cerevisiae the uptake of xylose (15 g 1" ) was severely retarded until the glucose concentration fell below 10 g 1" [110]. 

The absorption and transport of the majority of drugs across biological membranes occurs by passive diffusion, a process dependent upon physicochemical properties, i.e., lipophilicity, ionization, and molecular size. Since enantiomers have identical physicochemical properties, stereoselectivity would not be expected even though membrane phospholipids are chiral, the significance of lipophilieity appears to outweigh that of compound chirality. In contrast, differences between diastereoisomers may occur as a result of their differential solubility. However, in the case of compounds transported via earrier-mediated meehanisms, e.g., facilitated diffusion or active transport, proeesses involving a direct interaction between a substrate and a carrier maeromoleeule, stereoselectivity is expected. Preferential absorption of the l- eompared to the D-enantiomers of dopa [96] and methotrexate [97,98] have been reported. In the case of the above examples, enantioseleetivity in absorption is observed, whereas in the case of eephalexin, a eephalosporin antibiotic, diastereoselectivity for the L-epimer oeeurs. The L-epimer has shown a greater affinity than, and acted as a competitive inhibitor of o-eephalexin transport [99]. The L-epimer is also more suseeptible to enzyme-mediated hydrolysis, with the result that it cannot be detected in plasma [99]. 

Facilitated diffusion passive transport, the movement of specific compounds across a biomembrane from higher to lower concentration, but at a rate greater than simple diffusion. F. d. is saturable, meaning that above a certain concentration, the rate is not dependent on the substrate concentration. Furthermore, it is stereospecific and susceptible to competitive inhibition. Together, these properties indicate that the process is mediated by a carrier or pore protein in the membrane. F.d. differs from Active transport (see) in not requiring energy. A class of substances called lonophores (see) mimic the carriers of F.d. by making membranes permeable to certain ions. Antibiotics that act in this way are called transport antibiotics. 

On the other hand, if the products separate rapidly or react with other species (or catalysts) that generate the final product at a rate that is competitive with that of reversion to reactants, the overall rate of product formation will increase. Thus, the reaction of the product of the first step with a third entity can be the key to enhancing the rate, along with the conventionally expected stabilization of the transition state. In the extreme, if the reaction is made irreversible by a process that prevents the products from recombining, the net rate of product formation is greatly facilitated, allowing the full effect of catalysis to be observed in the net rate of transformation. The availability of routes that promote the forward reaction requires catalytic species be present in the vicinity of the initially formed complex because diffusion is expected to be slower than the separation of the immediate products. While such a situation is unusual with small catalysts, it is likely to be common with large catalysts, such as enzymes, where a catalytic array is present once the substrate has become associated (Scheme 1). 

These strategies are interesting for the production of H2 and 02 from water by a photoelectrochemical approach, but in the case of C02, it is necessary to (1) avoid the use of a liquid electrolyte (to eliminate problems of C02 solubility, diffusion limitation due to double layer, solvent competition, and to simplify cell sealing and facilitate product recovery eliminating the solvent), (2) have the anodic and cathodic reactions in separate compartments (reduce separation costs and eliminate safety... 

Physically, r is proportional to the ratio of mass transfer coefficient of liquid water in membrane to mass transfer coefficient of water vapour in the backing layer. The parameter r thus describes the competition of two opposite water fluxes back diffusion, which wets the anode side of the membrane and leakage through the backing layer to the channel, which facilitates membrane drying. Physically, r controls the local water-limiting current density (see below). 

Fimkes, M. Redone, D. Knezevic, J. Dobhnger, M. Rant, U. Electrically facilitated translocations of proteins through silicon nitride nanopores Conjoint and competitive action of diffusion, electrophoresis, and electroosmosis. Nano Lett 2010,10, 2162-2167. 

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