Lipid environment

These simulations revealed that AEA assumes an extended conformation in the bilayer, with its C16-C20 alkyl tail portion (located near the bilayer center) capable of considerable motion. During the simulation, AEA assumed many of the conformations discussed above for AA, including 

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General anaesthetics have been in use for the last 100 years, yet their mechanism of action are still not yet clearly defined. For many years it was thought that general anaesthetics exerted their effects by dissolving in cell membranes and perturbing the lipid environment in a non-specific manner. This theory derived from the observation that for a number of drugs which induced anaesthesia, their potency correlated with their oil-water partition coefficients. This Meyer-Oveiton correlation was accepted for a number of years, however in the last 15-20 years evidence has shown that a more likely theory is that of specific interactions of anaesthetics with proteins, particularly those within the CNS that mediate neurotransmission [1]. 

Viel, G.T., Yang, Q., Lundahl, P, Ensing, K., and de Zeeuw, R. A., Size-exclusion chromatographic reconstitution of the bovine brain benzodiazepine receptor. Effects of lipid environment on the binding characteristics, /. Chromatogr. A, 776, 101, 1997... 

In this book we will focus on physicochemical profiling in support of improved prediction methods for absorption, the A in ADME. Metabolism and other components of ADME will be beyond the scope of this book. Furthermore, we will focus on properties related to passive absorption, and not directly consider active transport mechanisms. The most important physicochemical parameters associated with passive absorption are acid-base character (which determines the charge state of a molecule in a solution of a particular pH), lipophilicity (which determines distribution of a molecule between the aqueous and the lipid environments), solubility (which limits the concentration that a dosage form of a molecule can present to the solution and the rate at which the molecule dissolves from... 

Ashikawa, I., J.-J. Yin, W. K. Subczynski, T. Kouyama, J. S. Hyde, and A. Kusumi. 1994. Molecular organization and dynamics in bacteriorhodopsin-rich reconstituted membranes Discrimination of lipid environments by the oxygen transport parameter using a pulse ESR spin-labeling technique. Biochemistry 33 4947 1952. 

In a lipid environment, van der Waals interactions become less specific. Electrostatic effects are enhanced up to 40-fold (according to Coulomb s law) due to the low dielectric constant, e s 2, of the hydrophobic core of membranes. As a result, weak electrostatic interactions, e.g., between the 71-electrons of an aromatic ring and a cation [51], may come into play. In addition, H-bond interactions, which can be considered as dipole-dipole interactions can also become relevant. 

Romsicki, Y., Sharom, F. J., The membrane lipid environment modulates drug interactions with the P-glycoprotein multidrug transporter, Biochemistry 1999, 38, 6887-6896. 

To diffuse rapidly in the plane of the membrane (lateral diffusion), a molecule must simply move around in the lipid environment (including the polar head groups). It need not change how it interacts with phospholipids or with water since it is constantly exposed to pretty much the same environment. Lateral diffusion can be slowed (or prevented) by interactions between membrane proteins and the cellular cytoskeleton. This spatially restricts a plasma membrane protein to a localized environment. 

Tomato was reported to exert antioxidant activity in some studies (Vinson and others 1998 Kahkonen and others 1999), whereas it showed no antioxidant activity or even acted as a pro-oxidant in others (Gazzani and others 1998). The antioxidant effect of tomato is most probably due to synergism between several compounds and not due to lycopene content alone, as pure lycopene and several other carotenoids act as pro-oxidants in a lipid environment (Al-Saikhan and others 1995 Haila and others 1996). 

Rhodopsin in photoreceptors is immersed in a lipid environment highly enriched in phospholipids containing docosahexaenoic acid, which is essential for rhodopsin function 587... 

The results presented in this chapter demonstrate that enhanced immunogenic efficacy can be achieved by using liposphere-based formulations, indicating the potential usefulness of lipospheres in the formulation of human and veterinary vaccines. The liposphere approach employs the fat-lipid environment to achieve several goals to serve as a carrier to protect the antigen, to serve as a depot, and to provide a surface interphase necessary for adjuvant activity. The ability to provide different surface... 

E. London and G. W. Feigenson, Fluorescence quenching in model membranes. 2. Determination of the local lipid environment of the calcium adenosinetriphosphatase from sarcoplasmic reticulum, Biochemistry 20, 1939-1948 (1981). 

Maneri, L.R. and P.S. Low. 1988. Structural stability of the erythrocyte anion transporter, band 3, in different lipid environments. A differential scanning calorimetric study. J Biol Chem 263 16170-16178. 

Vandenbussche G, Clercx A, Clercx M, et al. Secondary structure and orientation of the surfactant protein SP-B in a lipid environment. A Fourier transform infrared spectroscopy study. Biochemistry 1992 31(38) 9169-9176. 

Testosterone metabolism. The lipido-ste-rol extract (LSESr, Permixon) was studied in primary cultures of epithelial cells and fibroblasts separated from benign prostate hypertrophy and prostate cancer tissues. The extract inhibited the formation of the T metabolites androstenedione 5 4 and 5 a-DHT The lipophilic extracts of fruits inhibited T 5p-reductase (EC 1.3.99.5) (5(xR). For fatty acid-like 5(xR inhibition a strongly polar end-group and a molecular skeleton allowing nonpolar interactions with the enzyme were required. The result indicated that 5pR activity in prostatic tissue may be influenced by the lipid environ-... 

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