Passive diffusion across cell membranes

Because macromolecular carriers normally cannot enter cells by passive diffusion across the plasma membrane, the general mechanism for passing the cell membrane is endo-cytosis. Endocytosis is a way in which the cells take up large materials like micelles by folding the cell membrane inward,... 

Traditional view of sodium and potassium movement across a cell membrane. Passive diffusion occurs because of concentration gradients across the membrane. A sodium-potassium pump, powered by ATP, moves sodium and potassium against their concentration gradients. (From Campbell, N.A. et al.. Biology, 5th edn., Addison Wesley Longman, Menlo Park, CA, 1999. With permission.)... 

Among the trace metals, Hudson and Morel [7] postulated that Fe and Zn were closest to a diffusion-limited situation based upon measured cellular metal quotas and concentrations in marine systems (e.g. Zn would be diffusion limited for cells > 20 pm). Similarly, Hassler and Wilkinson [90] showed that for cells grown under conditions of Zn starvation, transport was diffusion limited for [Zn2+] < 10 12 mol dm. Fortin and Campbell [91] showed that, in the presence of chloride, the Ag transport flux to Chlamydomonas reinhardtii was close to a diffusion limitation at the lower Ag concentrations that were examined. Diffusion limitation of trace metals is most likely in systems where the concentrations are low and concentrations of competing metals are high, especially for essential metals that are taken up by passive diffusion across the membrane [8], The final point of essentiality could be especially important when transport systems are upregulated in response to lowmetal concentrations (see also Section 2.2 [90,92]). 

The main obstacle to percntaneous penetration of water and xenobiotics is the onter-most membrane of the epidermis. This is called the stratum comeum. All entry of substances through the stratum comeum occurs by passive diffusion across several cell layers. The locus of entry varies, depending on the chemical properties of xenobiotics. Polar substances are believed to penetrate cell membranes through the protein filaments nonpolar ones enter through the hpid matrix. Hydration of the stratnm comenm increases its permeability for polar substances. Electrolytes enter mainly in a nonionized form, and thus the pH of the solution applied to the skin affects permeabUity. Many hpophdic substances, such as carbon tetrachloride and organophosphate insecticides, readily penetrate the stratum comeum. Pretreatment of the skin with solvents, snch as dimethyl sulfoxide, methanol, ethanol, hexane, acetone, and, in particular, a mixture of chloroform and methanol, increases permeability of the skin (Loomis, 1978). 

Low molecular weight and lipophilic drag molecules are usually absorbed transcellularly, by passive diffusion across the epithelial cells. With respect to passive diffusion, the outer membrane of the epithelial cell may be regarded as a layer of lipid, surrounded on both sides by water (Figure 1.4). Thus for transport through the apical membrane, there are three barriers to be circumvented ... 

For most membranes, passive diffusion is the main mechanism by which drug traverses membrane barriers. The process of passive diffusion initially involves partition of a drug between the aqueous fluid at the site of the application and the lipoidal cell membrane. The drug in solution in the membrane then diffuses across the membrane followed by a second partition of drug between the membrane and the aqueous fluids within the site of absorption. 

Since both Phase I and II biotransformation processes can increase the polarity and, accordingly, the aqueous solubility of the toxicant, these biotransformations can essentially trap the toxicant in the cell by compromising its ability to passively diffuse across the surface membrane of the cell. The cellular elimination of toxicants is facilitated by membrane proteins that actively transport Phase I and II biotransformation products out of the cell and make them available for elimination from the body. The active cellular elimination processes are often referred to as Phase III detoxification/elimination processes. 

Most body tissues are protected by lipophilic barriers that serve as the body s primary protection against absorption of chemicals. It is well established that lipophilic chemicals can penetrate lipophilic barriers (including mucous membranes) much more readily than can hydrophilic chemicals by passively diffusing across lipid-rich cell membranes. 2 4l The lipid-rich mucous membranes also serve as barriers to the absorption of hydrophilic species. Lipophilic chemicals, however, promote the permeation of hydrophilic chemicals that are dissolved in the lipophiles. Lipophiles are routinely used, for example, in drug delivery systems (see Section 3.3). 

Release. It is presently believed that a neurotransmitter is released during the exocytotic process from the presynaptic membrane in discrete quanta, or finite amounts these quanta are released spontaneously in nerves at rest at the rate of approximately one or two per second. Excited nerves increase the quantal release of transmitter by about fivefold. It has been estimated that at the neuromuscular junction each quantum contains about 10 molecules (0.166 X 10 mol) of the transmitter acetylcholine. It is also established that neurotransmitters such as acetylcholine can passively diffuse across the cell membrane by mechanisms unrelated to exocytosis. The number of moles of transmitter per quantal release for neurotransmitters in the central nervous system has not been accurately quantified. 

General reaction mechanism of the PPIs with the H,K ATPase in the membrane of the parietal cell canaliculus, showing passive diffusion across the canalicular membrane, accumulation of the protonated form, conversion to the sulfenamide, and reaction with one or more cysteines in the catalytic subunit of the H,K ATPase. The outline of the pump structure illustrates the vestibule of the pump on its outside surface where binding of the PPIs results in inhibition of acid secretion correlated with inhibition of ATPase activity. 

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