Transport Across Lipid Membranes

The velocity of diffusion across a membrane depends on the size of the respective molecule and its relative solubility vdthin the lipid phase. Small nonpolar molecules exhibit good lipid solubility and have a rather high velocity of diffusion. Uncharged polar molecules such as H 2O or CO2, which have a rather low lipid solubility, may also cross a membrane by passive diffusion. In contrast, charged molecules and ions 

Water phase Lipid membrane 2. Water phase 

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Under physiological conditions, i.e., in neutral aqueous solution with a. significant p02, ferric ion (Fe ) is the predominant species and ferrous ion (Fe ) can only exist if protected from oxidation by specific coordination (Schneider 1988). Transient, enzymatic reduction of Fe " serves as a control point for the exchange of iron, for example in the mobilization of iron from ferritin stores and transport across lipid membranes. This is important in that most chelators presently in use or under investigation display sped-... 

In a conceptual paper, Matile et al. described that CT-DNA can be activated by amphiphilic cations such as guanidiniocalixarenes 7 to act as a cation transporter in bulk and Upid bilayer membranes and showed that this unusual activity of DNA can be of interest for the development of biosensors (Fig. 24.32). In light of the chargebalancing effect of cell-penetrating peptides as anion transporters across lipid membranes, this discovery demonstrates that the multifunctionality of polyion-counterion complexes is general and occurs with low-basicity polyanions exactly as with low-acidity polycations [100]. 

The Energetics Problem of Cation Transport Across Lipid Bilayer Membranes A qualitative perspective of the barrier presented by a lipid bilayer membrane can be obtained from the Bom expression2) for solvation energy, SE,... 

With the adequacy of lipid bilayer membranes as models for the basic structural motif and hence for the ion transport barrier of biological membranes, studies of channel and carrier ion transport mechanisms across such membranes become of central relevance to transport across cell membranes. The fundamental principles derived from these studies, however, have generality beyond the specific model systems. As noted above and as will be treated below, it is found that selective 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. 

Much interest for ion transport has its origin in the field of crown ether chemistry. Therefore, most model studies of ion channels have been more or less based on crown ether chemistries. Pioneering work has been undertaken by Fylcs, who not only synthesized varieties of gigantic molecules starting from crown ethers, " but established a method of the rate assay for ion transport across lipid bilayer membranes, a pH sCat technique. Vesicles having different inside and outside... 

In general, the specific constituents of milk are synthesized from small molecules absorbed from the blood. These precursors are absorbed across the basal membrane but very little is known about the mechanism by which they are transported across the membrane. Since the membrane is rich in lipids, and precursors are mostly polar with poor solubility in lipid, it is unlikely that the precursors enter the cell by simple diffusion. It is likely, in common with other tissues, that there are specialized carrier systems to transport small molecules across the membrane such carriers are probably proteins. 

Research continues in an effort to gain a more thorough understanding of how lipoproteins arc synthesized how lipids are arranged and combined with proteins to form cell membranes what specific role lipids play in transport across cell membranes how hormones act to regulate lipid metabolism, the biochemical basis of such abnormal lipid metabolic states as Gaucher s disease. Nieniann-Pick s disease, etc. how lipids per sc permeate cell membranes anil huw many phenotypic lipoproteins occur in serum. 

Signal sequences usually occur at the amino terminus of polypeptides to be transported. These sequences vary in length from 10 to 40 amino acid residues and are generally characterized by the occurrence of a block of hydrophobic residues. The presence of hydrophobic residues reflects the fact that protein transport invariably involves the movement of proteins across lipid membranes. The hydrophobic residues both target the protein to the appropriate compartment and initiate penetration into the membrane. 

Ions and small molecules may be transported across cell membranes or lipid bilayers by artificial methods that employ either a carrier or channel mechanism. The former mechanism is worthy of brief investigation as it has several ramifications in the design of selectivity filters in artificial transmembrane channels. To date there are few examples where transmembrane studies have been carried out on artificial transporters. The channel mechanism is much more amenable to analysis by traditional biological techniques, such as planar bilayer and patch clamp methods, so perhaps it is not surprising that more work has been done to model transmembrane channels. 

Lipinski s upper bounds on the numbers of hydrogen bond donors and acceptors can be related to the ability of a molecule to penetrate lipid membranes. Molecules which have groups which can form hydrogen bonds, bind to water free energy will be required to displace the water as the molecule is transported across the membrane. This energy expensive process can become limiting if too many water molecules have to be removed. Only in special cases, such as that of cyclosporin [9] does internal... 

At physiological pH, the ionophores are ionized with the fat-soluble part of the molecule residing in the lipid bilayer of the membrane and the ionized moiety in the aqueous milieu (4). Binding of the metal ion takes place at the membrane surface As successive ether oxygen atoms from the ionophore bind to the metal, it loses its solvated water molecules, thereby forming a neutral zwitterionic metal-ionophore complex. Transport across the membrane can now take place, and at the opposite surface, the process is reversed to leave the metal cation and the anionic ionophore on the other side of the membrane. The... 

Transient water pores in cellular membranes are involved in several relevant processes, such as maintenance of osmotic balance, drug and antibody delivery into cells, and ion transport across the membrane. Understanding ion transport across membranes is especially important, because membranes strive to maintain a cationic electrochemical gradient used for ATP synthesis. Yet, ions leak through lipid membranes, and understanding the mechanisms associated with ion leakage would allow one to control membrane properties better in related applications. 

As discussed in Chapter 12. some molecules can pass through cell membranes because they dissolve in the lipid bilayer. Such molecules are called lipophilic molecules. The steroid hormones provide a physiological example. These cholesterol relatives can pass through a membrane in their path of movement, but what determines the direction in which they will move Such molecules will pass through a membrane located down their concentration gradient in a process called simple diffusion. In accord with the Second Law of Thermodynamics, molecules spontaneously move from a region of higher concentration to one of lower concentration. Thus, in this case, an entropy increase powers transport across the membrane. 

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