Diffusion across membranes

Most transporters are proteins. Small proteins can bind some substance on one side of a membrane, diffuse across the membrane, and then release that substance on the other side. Such mobile carriers may bind a single substance, or they may bind two different substances, like the proton-solute symporter portrayed in Figure 3-l4a. Candidates for transport by a proton symporter in plants include inorganic ions such as Cl- and metabolites such as sugars and amino acids. Many substances apparently move in pores or channels, which can be membrane-spanning proteins. Some channels can have a series of binding sites, where the molecule or molecules transported go from site to site through the membrane (Fig. 3-l4b). As another... 

Reverse osmosis (and nanofiltration) by contrast operate by diffusion from a solution. Under the high differencial pressure across the membrane, the solvent from the solution actually dissolves in the material of the membrane, diffuses across it and transfers out into the clean solvent on the ocher side. It is not a perfect separation, because the dissolved species from the feed solution have a definite ability to diffuse through it as well, but the diffusion coefficient for the solvent is so much higher than that for the solute that the separation is virtually complete. 

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 ... 

Salt flux across a membrane is due to effects coupled to water transport, usually negligible, and diffusion across the membrane. Eq. (22-60) describes the basic diffusion equation for solute passage. It is independent of pressure, so as AP — AH 0, rejection 0. This important factor is due to the kinetic nature of the separation. Salt passage through the membrane is concentration dependent. Water passage is dependent on P — H. Therefore, when the membrane is operating near the osmotic pressure of the feed, the salt passage is not diluted by much permeate water. 

Aquatic organisms, such as fish and invertebrates, can excrete compounds via passive diffusion across membranes into the surrounding medium and so have a much reduced need for specialised pathways for steroid excretion. It may be that this lack of selective pressure, together with prey-predator co-evolution, has resulted in restricted biotransformation ability within these animals and their associated predators. The resultant limitations in metabolic and excretory competence makes it more likely that they will bioacciimiilate EDs, and hence they may be at greater risk of adverse effects following exposure to such chemicals. 

Certain molecules freely diffuse across membranes, but the movement of others is restricted because of size, charge, or solubility. 

Although a portion of the nutrients released from feedstuff s is absorbed by diffusing across the apical membrane of enterocytes or through the junctional complexes of adjacent enterocytes (paracellular absorption), the majority of nutrients are absorbed from the lumen of the GIT by carrier proteins that are inserted into the apical membrane of enterocytes and colonocytes. 

Process Description Pervaporation is a separation process in which a liquid mixture contacts a nonporous permselective membrane. One component is transported through the membrane preferentially. It evaporates on the downstream side of the membrane leaving as a vapor. The name is a contraction of permeation and evaporation. Permeation is induced by lowering partial pressure of the permeating component, usually by vacuum or occasionally with a sweep gas. The permeate is then condensed or recovered. Thus, three steps are necessary Sorption of the permeating components into the membrane, diffusive transport across the nonporous membrane, then desorption into the permeate space, with a heat effect. Pervaporation membranes are chosen for high selectivity, and the permeate is often highly purified. 

The basic flux across the membranes may be related to that across a thin film [83]. Pick s First Law of Diffusion indicates that the total flux of diffusant across a homogeneous membrane, /, is proportional to the concentration gradient of the diffusant ... 

FIG. 14 A model for the uptake of weakly basic compounds into lipid bilayer membrane (inside acidic) in response to the pH difference. For compounds with appropriate pki values, a neutral outside pH results in a mixture of both the protonated form AH (membrane impermeable) and unprotonated form A (membrane permeable) of the compound. The unprotonated form diffuse across the membrane until the inside and outside concentrations are equal. Inside the membrane an acidic interior results in protonation of the neutral unprotonated form, thereby driving continued uptake of the compound. Depending on the quantity of the outside weak base and the buffering capacity of the inside compartment, essentially complete uptake can usually be accomplished. The ratio between inside and outside concentrations of the weakly basic compound at equilibrum should equal the residual pH gradient. 

W. Stein, Transport and Diffusion across Cell Membranes, Academic Press, Orlando, FL, 1986. 

A thorough discussion of the mechanisms of absorption is provided in Chapter 4. Water-soluble vitamins (B2, B12, and C) and other nutrients (e.g., monosaccharides, amino acids) are absorbed by specialized mechanisms. With the exception of a number of antimetabolites used in cancer chemotherapy, L-dopa, and certain antibiotics (e.g., aminopenicillins, aminoceph-alosporins), virtually all drugs are absorbed in humans by a passive diffusion mechanism. Passive diffusion indicates that the transfer of a compound from an aqueous phase through a membrane may be described by physicochemical laws and by the properties of the membrane. The membrane itself is passive in that it does not partake in the transfer process but acts as a simple barrier to diffusion. The driving force for diffusion across the membrane is the concentration gradient (more correctly, the activity gradient) of the compound across that membrane. This mechanism of... 

Two principal routes of passive diffusion are recognized transcellular (la —> lb —> lc in Fig. 2.7) and paracellular (2a > 2b > 2c). Lateral exchange of phospholipid components of the inner leaflet of the epithelial bilayer seems possible, mixing simple lipids between the apical and basolateral side. However, whether the membrane lipids in the outer leaflet can diffuse across the tight junction is a point of controversy, and there may be some evidence in favor of it (for some lipids) [63]. In this book, a third passive mechanism, based on lateral diffusion of drug molecules in the outer leaflet of the bilayer (3a > 3b > 3c), wih be hypothesized as a possible mode of transport for polar or charged amphiphilic molecules. 

Biegel, C. M. Gould, J. M., Kinetics of hydrogen ion diffusion across phospholipid vesicle membranes, Biochemistry 20, 3474-3479 (1981). 

Membrane transport represents a major application of mass transport theory in the pharmaceutical sciences [4], Since convection is not generally involved, we will use Fick s first and second laws to find flux and concentration across membranes in this section. We begin with the discussion of steady diffusion across a thin film and a membrane with or without aqueous diffusion resistance, followed by steady diffusion across the skin, and conclude this section with unsteady membrane diffusion and membrane diffusion with reaction. 

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