Nonpolarized cells, transport

Drug molecules are transported across cell membranes. Because of the lipid bilayer construction of the membrane (Appendix 2), nonpolar (lipid-soluble) molecules are able to diffuse and penetrate the cell membrane. Polar molecules, however, cannot penetrate the cell membrane readily via passive diffusion and rely on other transport mechanisms. 

Phospholipids are ideal compounds for making membranes because of their amphipathic nature (see chapter 17). The polar head-groups of phospholipids prefer an aqueous environment, whereas the nonpolar acyl substituents do not. As a result, phospholipids spontaneously form bilayer structures (see fig. 17.6), which are a dominant feature of most membranes. The phospholipid bilayer is the barrier of the cell membrane that prevents the unrestricted transport of most molecules other than water into the cell. Entry of other molecules is allowed if a specific transport protein is present in the cell membrane. Similarly, the phospholipid bilayer prevents leakage of metabolites from the cell. The amphipathic nature of phospholipids has a great influence on the mode of their biosynthesis. Thus, most of the reactions involved in lipid synthesis occur on the surface of membrane structures catalyzed by enzymes that are themselves amphipathic. 

The permeability, P (P = Pc x D), of a nonpolar substance through a cell membrane is dependent on two physicochemical factors (1) solubility in the membrane (Pc), which can be expressed as a partition coefficient of the drug between the aqueous phase and membrane phase, and (2) diffusivity or diffusion coefficient (D), which is a measure of mobility of the drug molecules within the lipid. The latter may vary only slightly among toxicants, but the former is more important. Lipid solubility is therefore one of the most important determinants of the pharmacokinetic characteristics of a chemical, and it is important to determine whether a toxicants is readily ionized or not influenced by pH of the environment. If the toxicant is readily ionized, then one needs to understand its chemicals behavior in various environmental matrices in order to adequately assess its transport mechanism across membranes. 

A for K, Rb , and Cs and 5.5—7.4 A for Na and Li . It is understandable that the cavity fits in with K. Carbonyl groups are distributed along the inside wall of the cavity which is necessarily polar. Aliphatic side dtains form the outside wall of the bracelet whidi is necessarily nonpolar. Valinomycin binds K in the hydro-0ulic interior of the cavity and transports the ion across the lipid bilayer of the cell... 

Living cells are surrounded by membranes and on either side of the membrane an aqueous environment is present. The interior of the membrane is highly nonpolar. Based on the result of Problem 15, can you explain why it is difficult to transport or move charges across a membrane in a living cell (Contractor)... 

Skibbens, J.E., Roth, M.G. and Matlin, K.S. (1989) Differential extractability of influenza vims hemagglutinin during intracellular transport in polarized epithelial cells and nonpolar fibroblasts. J. Cell Biol. 108, 821-832. 

How does a polar molecule or ion in the water outside a cell pass through the nonpolar interior of the ceU membrane and enter the cell Some nonpolar molecules like O2 are small enough to enter and exit the cell by diffusion. Polar molecules and ions, on the other hand, may be too large or too polar to diffuse efficiently. Some ions are transported across the membrane with the help of molecules called ionophores. 

Cholesterol is essential to life because it forms an important component of cell membranes and is the starting material for the synthesis of all other steroids. Humans do not have to ingest cholesterol, because it is synthesized in the liver and then transported to other tissues through the bloodstream. Because cholesterol has only one polar OH group and many nonpolar C-C and C-H bonds, it is insoluble in water (and, thus, in the aqueous medium of the blood). 

Biological cell membranes are multi-component systems consisting of a fluid bilayer lipid membrane (BLM) and integrated membrane proteins. The main structural features of the BLMs are determined by a wide variety of amphiphilic lipids whose polar head groups are exposed to water while hydrocarbon tails form the nonpolar interior. The BLMs act as the medium for biochemical vectorial membrane processes such as photosynthesis, respiration and active ion transport. However, they do not participate in the corresponding chemical reactions which occur in membrane-dissolved proteins and often need redox-active cofactors. BLMs were therefore mostly investigated by physical chemists who studied their thermodynamics and kinetic behaviour . ... 

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