Diffusion, passive transmembrane

Three types of membrane transporter are found channels, carriers and pumps (Fignre 6.10). Channels are transmembrane proteins that function as selective pores throngh which ions or uncharged molecules can diffuse passively. Their selectivity for solutes depends on the size of the pore and the density of surface charges lining it. These are altered in response to external and internal stimuli in the plant, so regnlating the transport. 

Extensive research has established the relationship between the extent of distribution of compounds and their physicochemical properties. With this information, Vdss can be quite successfully predicted using in silico models [27-30], In silico prediction of distribution is based on physicochemical properties that relates to passive transmembrane diffusion and tissue binding, and it only predicts Vdss. The other factors that contribute to distribution, such as transporter-mediated distribution, were not taken into account. These algorithms are based on the assumption that all compounds will dissolve in intra- and extracellular tissue water, and the unionized portion will partition into the neutral lipids and neutral phospholipids located within tissue cells. For compounds categorized as a strong base (at least one basic group (p/fa >7), an additional mechanism of electrostatic interaction with tissue acidic phospholipids is incorporated. Acids and weak bases are assumed... 

Passive transmembrane diffusion is the ability of a compound to cross a membrane bilayer in a way solely driven by concentration gradient, as described by Pick s law of diffusion. No special molecules assist in this transport, nor is any type of energy input required, just nature s tendency to equalize concentrations on both sides of a semiperme-able barrier. This simple process turns out to be the major mechanism by which most drugs can enter and exit cells. 

Passive transmembrane diffusion Ability to cross a membrane bilayer in a concentration gradient-driven fashion Usually the major component of ceU permeability and drug absorption lAM, PAMPA... 

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). 

Passive diffusion - passive transport driven by a difference in concentration of the element between the two sides of the luminal membrane and the mucosa. Transmembrane movement of ions occurs through pores or channels within the membrane and is an energy-independent process. A significant amount of passive... 

Fig. 5. Tentative mixed potential model for the sodium-potassium pump in biological membranes the vertical lines symbolyze the surface of the ATP-ase and at the same time the ordinate of the virtual current-voltage curves on either side resulting in different Evans-diagrams. The scale of the absolute potential difference between the ATP-ase and the solution phase is indicated in the upper left comer of the figure. On each side of the enzyme a mixed potential (= circle) between Na+, K+ and also other ions (i.e. Ca2+ ) is established, resulting in a transmembrane potential of around — 60 mV. This number is not essential it is also possible that this value is established by a passive diffusion of mainly K+-ions out of the cell at a different location. This would mean that the electric field across the cell-membranes is not uniformly distributed.

Fischer, H., Passive diffusion and active transport through biological membranes - Binding of drugs to transmembrane receptors, PhD Thesis,... 

The octanol/buffer represents a partition coefficient between two bulk phases it is less affected by the structure of the analyte and therefore it cannot be used to predict the exact value of liposome membrane-to-buffer Xp, which is also affected by the geometry of the analyte (41 4). However, it is accepted and established that the octanol-to-buffer can help to predict transmembrane passive diffusion (40). In the case of liposomes such as Doxil, in which the internal aqueous phase (intraliposome aqueous phase) is different from the external liposome aqueous medium due to large differences in the composition and pH of these two aqueous phases, there are two different liposome membrane-to-aqueous phase partition coefficients this is referred to as asymmetry in the membrane-to-aqueous media partition coefficient. 

Membranes play essential roies in the functions of both prokaryotic and eukaryotic cells. There is no unicellular or multicellular form of life that does not depend on one or more functional membranes. A number of viruses, the enveloped viruses, also have membranes. Cellular membranes are either known or suspected to be involved in numerous cellular functions, including the maintenance of permeability barriers, transmembrane potentials, active as well as specific passive transport across the membranes, hornione-receptor and transmitter-receptor responses, mitogenesis, and cell-cell recognition. The amount of descriptive material that might be included under the title of biological membranes is encyclopedic. The amount of material that relates or seeks to relate structure and function is less, but still large. For introductory references see Refs. 53, 38, 12, 47, 34, 13. Any survey of this field in the space and time available here is clearly out of the question. For the purposes of the present paper we have selected a rather narrow, specific topic, namely, the lateral diffusion of molecules in the plane of biological mem-branes.38,12,43,34 We consider this topic from the points of view of physical chemistry and immunochemistry. 

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... 

In the tissue cross-reactivity studies, the antibody has equal access to all tissues and all cell components (membrane, cytosol, nucleus) of the tissues on the section. This is not true in vivo where access to the tissues is governed by passive diffusion of the antibody to the tissue. Moreover, unless uptake by tissues is receptor-mediated, cell membranes preclude entrance of an antibody into the cells. In addition there are blood-brain, blood-nerve, blood-eye, and blood-testis barriers characterized by specialized endothelium that reduce movement of immunoglobulin into these protected spaces. Thus, some tissues have relatively little access by antibodies compared to others. Likewise, antigens within cells have little chance of access to the antibody compared to cell membrane or transmembrane antigens. 

In real cells, multiple transmembrane pumps and channels maintain and regulate the transmembrane potential. Furthermore, those processes are at best only in a quasi-steady state, not truly at equilibrium. Thus, electrophoresis of an ionic solute across a membrane may be a passive equilibrative diffusion process in itself, but is effectively an active and concentra-tive process when the cell is considered as a whole. Other factors that influence transport across membranes include pH gradients, differences in binding, and coupled reactions that convert the transported substrate into another chemical form. In each case, transport is governed by the concentration of free and permeable substrate available in each compartment. The effect of pH on transport will depend on whether the permeant species is the protonated form (e.g., acids) or the unprotonated form (e.g., bases), on the pfQ of the compound, and on the pH in each compartment. The effects can be predicted with reference to the Henderson-Hasselbach equation (Equation 14.2), which states that the ratio of acid and base forms changes by a factor of 10 for each unit change in either pH or pfCt ... 

Serotonin binds to the platelet 5-HTj receptor coupled to PLC via a G protein. The human serotonin receptor has been cloned and have the usual seven transmembrane domain form (Saltzman et al., 1991). Serotonin is rapidly taken up by passive diffusion and by a high affinity eneigy-dependent carrier, and is released upon platelet activation by secretion ftom the dense granules (Pletscher, 1987). 

For most polar molecules, the lipid bilayer of a cell membrane represents an impermeable membrane, which uncharged molecules can cross only by passive diffusion. During evolution, transport pathways also emerged allowing polar molecules, such as nutrients or metabolites, to cross a cell membrane. As a result, the transport of small molecules is mediated by transmembrane proteins, whereas macromolecules and small particles cross membranes by various cytotic mechanisms. 

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