Transmembrane transport diffusion

The ideas of Overton are reflected in the classical solubility-diffusion model for transmembrane transport. In this model [125,126], the cell membrane and other membranes within the cell are considered as homogeneous phases with sharp boundaries. Transport phenomena are described by Fick s first law of diffusion, or, in the case of ion transport and a finite membrane potential, by the Nernst-Planck equation (see Chapter 3 of this volume). The driving force of the flux is the gradient of the (electro)chemical potential across the membrane. In the absence of electric fields, the chemical potential gradient is reduced to a concentration gradient. Since the membrane is assumed to be homogeneous, the... 

Many experimental variations are possible when performing uptake studies [246]. In a simple experiment for which the cells are initially free of internalised compound, the initial rates of transmembrane transport may be determined as a function of the bulk solution concentrations. In such an experiment, hydrophilic compounds, such as sugars, amino acids, nucleotides, organic bases and trace metals including Cd, Cu, Fe, Mn, and Zn [260-262] have been observed to follow a saturable uptake kinetics that is consistent with a transport process mediated by the formation and translocation of a membrane imbedded complex (cf. Pb uptake, Figure 6 Mn uptake, Figure 7a). Saturable kinetics is in contrast to what would be expected for a simple diffusion-mediated process (Section 6.1.1). Note, however, that although such observations are consistent... 

Ester prodrugs are employed to enhance membrane permeation and transepithelial transport of hydrophilic drugs by increasing the lipophilicity of the parent compound, resulting in enhanced transmembrane transport by passive diffusion. For example, pivampicillin, a pival-oyloxymethyl ester of ampicillin, is more lipophilic than its parent ampicillin and has demonstrated increased membrane permeation and transepithelial transport in in vivo studies.103... 

Thus molecules which assume a compact conformation will have a lower molecular volume and thus a higher diffusivity. An important consequence of this property is that even if such molecules have a high molecular weight (i.e. above the molecular weight threshold of 500 Da normally the cut-off limit for transmembrane transport), their high diffusivity may nevertheless be able to facilitate absorption. 

The first method employs the ballistic gun (2,3), where cells are exposed to ballistic bombardment by microparticles coated with the molecules of choice (e g., DNA). The second method is based on exposing the cells to ultrasound leading to an increased transmembrane transport (4). The third approach is based on an electrically driven process (electroporation), where cells are exposed to high-electric fields for short durations of micro- to milliseconds (5). This exposure leads to induction of short-lived permeability changes in the membrane ( pores ) enabling the diffusion of molecules across the membrane along their electrochemical gradients. 

The action of NE at adrenergic receptors is terminated by a combination of processes, including uptake into Ihe neuron and into cxtraneuronal lis.sucs. diffusion away from the synapse. and metabolism. Usually. Ihe primary mechanism for termination of Ihe action of NE is rcuplakc of the catecholamine into tlie nerve terminal. This procc.ss is termed upuike-l and involves a Na /Cl -dcpendenl transmembrane transporter that has a high affinity for NE. This uptake system also transparts certain amines other than NE into the... 

Many transmembrane transporter proteins, termed secondary transporters, use the discharge of an ionic gradient to power the uphill translocation of a solute molecule across membranes. Couphng solute movement to ion transport enables these secondary transporters to concentrate solutes by a factor of 10 with a solute flux 10 faster than by simple diffusion. We have already encountered the co-transport of leucine and Na+ by LeuT, but there are many other examples. Sugars and amino acids can be transported into cells by Na+-dependent symports. Dietary glucose is concentrated in the epithelial cells of the small intestine by a Na -dependent symport, and is then... 

The mechanism of uptake of fatty acids by the cell is not completely understood. Transport of fatty acids across the endothelial cells, the interstitial space, and the plasmalemma of the parenchymal cells is most likely a diffusion-like process (Van der Vusse et al., 1992). Recent experimental findings indicate that (1) specific membrane proteins are involved in transmembrane transport and (2) the uptake of fatty acids by brain is limited by the blood-brain barrier. 

Transport Properties. Important transmembrane transport parameters of the fibers are Lp, the hydraulic conductivity Pm, the diffusive permeability for a given solute o, the solute reflection coefficient and R, the solute rejection. These coefficients appear in the following equations, which are assumed to be valid at the steady state at each position Z along the fiber wall ... 

Here we suggest that ions or molecules temporarily bound to the membrane surface may have their transmembrane movement enhanced by pore formation and that this possible mechanism also has catalytic features. This additional hypothesis envisions that local membrane conformational changes can result from both the local transmembrane voltage and the surface binding of a transported molecule (S). That is, a pore-substrate complex is formed. One possible outcome is transmembrane transport in which S is temporarily bound to the inner surface of a pore, with subsequent electrical lateral motion (relative to the pore inner surface) by diffusion or lateral drift to the other side. Alternatively, as a pore shrinks and closes, S is presented to the other side of the membrane. In either case, upon dissociation, transport of S will have been accomplished. 

Neutral lonophores. The relationship between equilibrium ionophore affinities and dynamic biological transmembrane transport is detailed in Figure 2. The transport cycle catalyzed by neutral ionophores is given on the left. Ionophore added to a biological membrane partitions predominately into the membrane. A portion of the ionophore diffuses to the membrane Interface where it encounters a hydrated cation. A loose encounter complex is formed followed by replacement of the cationic hydration sphere by engulfment of the cation by the ionophore. The dehydrated complex is lipid-soluble and hence can diffuse across the membrane. The cation is then rehydrated, released, and the uncomplexed lono-phore freed to return to its initial state within the membrane. 

As sorption equilibria exist on both sides of the membrane, the overall rate of the transmembrane transport is determined by the diffusion step only. Fick s law can be used to describe the diffusional transport of a comjxment i through the membrane... 

Transcellular transport mechanisms are responsible for the transport of free amino acids through epithelial cells and are mainly present in cells of the intestinal mucosa and the renal tubules. Most amino acids are transported via a sodium-dependent transport system. However, sodium-independent transport and passive diffusion exist. Transmembrane transporters may be specific for single amino acids (e.g. histidine, glycine) or for groups of amino acids (e.g. dibasic amino acids, dibasic amino acids and cystine, neutral amino acids or dicarboxylic amino acids). 

The theoretical description of the kinetics of transmembrane transport through a liquid membrane should be based on the principles of solvent extraction kinetics. It should be determined by the processes at both water/membrane interphases and should also involve the intermediate step of diffusion in the membrane. Thus the existence of all these three steps makes the membrane system and its description much more complicated than the relatively simple water/organic phase. However, even the kinetics mechanism in simpler extraction systems is often based on the models dealing only with some limiting situations. As it was pointed out in the beginning of this paper, the kinetics of transmembrane transport is a fimction both of the kinetics of various chemical reactions occurring in the system and of diffusion of various species that participate in the process. The problem is that the system is not homogeneous, and concentrations of the substances at any point of the system depend on the distance from the membrane surface and are determined by both diffusion and reactions. The solution of a system of differential equations in this case can be a serious problem. 

Solution—Diffusion Model. In the solution—diffusion model, it is assumed that (/) the RO membrane has a homogeneous, nonporous surface layer (2) both the solute and solvent dissolve in this layer and then each diffuses across it (J) solute and solvent diffusion is uncoupled and each is the result of the particular material s chemical potential gradient across the membrane and (4) the gradients are the result of concentration and pressure differences across the membrane (26,30). The driving force for water transport is primarily a result of the net transmembrane pressure difference and can be represented by equation 5 ... 

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