Phospholipids acyl-chain

Chemical analysis of lipid composition has been described previously In detail. (Ill The technique employs der1 vat 1zat1 on by methylatlon of phospholipid acyl chains followed by separation and analysis with capillary gas chromatography. 

A second important series of experiments dealt with membrane chemistry composed of 5-cho1esten-3B-o1 (cholesterol) and partially oxidized phospholipid. The ultraviolet radiation Induced oxidation led to formation of hydroperoxide moieties at the unsaturated sites on some of the phospholipid acyl chains listed In Table II. The Cjg 2 chain was chosen as a reactive representative... 

The vibrational spectroscopy time scale (10-300 x 10 sec) is appropriate for the direct sampling of the fastest motion expected to occur in phospholipid acyl chains, namely trans-gauche isomerization. To date, most Raman ai)d FT-IR studies of phospholipid phase behavior and lipid/protein interaction have focused mainly on qualitative measures of acyl chain organization. For example, the... 

Fluorescence probes are frequently used to study changes in membrane organization and membrane fluidity induced by anesthetics, various drags, and insecticides. This technique measures fluidity as the rate and extent of phospholipid acyl chain excursion away from some initial chain orientation during the lifetime of the excited fluorescence state. Special techniques even allow the place of interaction to be localized, i.e. to the outer membrane region, the hydrophobic area, or the embedded proteins. 

Fig. 4.7 Location of amlo-dipine within the membrane bilayer derived from its cen-ter-of-mass location and crystal structure. Its location near the hydrocarbon corewater interface can facilitate both a hydrophobic interaction with the phospholipid acyl chain and an ionic interaction between the protonat-ed amino function of the drug and the charged anionic oxygen of the phosphate head group. Nimodipine structure and location are consistent with only hydrophobic interactions with the phospholipid acyl chains. No electrostatic interaction with the head groups of PI was noted. (Reprinted from Fig. 2 of ref. 95 with permission from the American Chemical Society.)...

Cholesterol affects a large variety of membrane properties in animal cells (39). It is involved in modifying dynamical membrane properties by reducing passive permeation, slowing down the lateral diffusion of molecules in fluid-like membranes, and speeding up diffusion in gel-phase membranes. It also affects bilayer properties by condensing the bilayer, which changes its elastic properties and promotes the order of phospholipid acyl chains in the hydrophobic membrane core. In this manner, cholesterol develops the formation of the liquid-ordered... 

The amphiphilic molecules can occur in lyotropic and thermotropic mesomorph, and the organization of lipid bilaycrs such as liposomes can exist in a temperature range where all the mesophases from gel state to liquid crystal state are favored. In the gel state the phospholipid acyl chains are closely packed and the molecular movements are deteriorized, while in the liquid crystalline slate, the fatty-acid moieties are in a more fluid stale and are able to move more freely. 

Modulation of Receptor Signaling by Phospholipid Acyl Chain Composition... 

Most biophysical studies of the effects of highly polyunsaturated phospholipid acyl chains on membranes have focused on changes in acyl chain packing, sometimes referred to as fluidity, a term which has no validity at the dimensions of the bimolecular leaflets... 

Both increased temperature and increased acyl chain unsaturation introduce disorder in phospholipid acyl chain packing thus, their effects on bilayer properties are often compared and discussed as being equivalent perturbations on the bilayer structure. However, detailed studies of the effect of these two factors on both intrachain order and acyl chain packing reveal significant differences. The difference between temperature-induced disorder and sn-2 unsaturafion-induced disorder of the saturated sn-1 acyl chain is illustrated in Fig. 2 A. The difference in NMR order-parameter data is plotted for each methyl group of the saturated 18 0 sn-1 acyl chain. The two difference curves show that the disorder caused by exchanging 18 ln-9 at the sn-2 position for 22 6n-3, occurs mainly... 

It is well established that cholesterol has a strong ordering effect on saturated phospholipid acyl chains in the fluid phase. This results in condensation of phospholipid mono-layers and a reduction in enthalpy of the main gel to liquid-crystalline phase transition. These effects are reduced as sn-2 acyl chain unsaturation is increased for phospholipids with a saturated sn-1 chain (Hemandez-Borrell et al., 1993 Smaby et al., 1997), although the proximity of the double bonds to the headgroup is as important as the number of double bonds (Stillwell et al., 1994). 

Numerous studies have been published describing modulation of membrane protein function by changes in the degree of unsaturation of the phospholipid acyl chains. It is... 

In visual signal transduction, activation proceeds from the receptor, rhodopsin, to the effector, phosphodiesterase (PDE), via the visual G protein, Gp Each Mil sequentially binds and activates up to 100 Gj, thus MII-Gj binding initiates the first stage of signal amplification in the visual pathway. Litman et al. (2001) have studied the phospholipid acyl chain dependence of the kinetics of formation of both the Mil conformation and the... 

Another type of interaction may be represented by protein kinase C, where a phospholipid acyl chain is proposed to extend up from the membrane to occupy a hydrophobic cavity in the protein. Seven different ways that a protein may interact with a biological membrane are represented schematically in Figure 3.8. 

Dufourc, E.J., Faucon, J.F., Fourche, G., Dufourcq, J., Gulik-Krywicki, T., Maire, M. Le. (1986). Reversible disc-to-vesicle transition of melittin-DPPC complexes triggered by the phospholipid acyl chain melting. FEBS Lett. 201 205-209. 

The temperature dependence of the order parameter profiles yields the isobaric thermal expansion coefficient an, according to Eq. (7). The data from the mixed phase collected in the last column of Table 1 are in broad agreement with thermal expansion eoefficients obtained from X-ray diffraction experiments in pure phospholipid bilayers [22,23] indicating that in the L,i-phase the phospholipid acyl chain motion is not constrained by an increasing proportion of the surfactant. 

Whatever application route is envivioned for the liposomal drugs, according to. Ref. 409 the following quality control assays should be applied to liposomal formulations for use in humans (1) Basic characterization assays pH osmolarity trapped volume phospholipid concentration phospholipid composition phospholipid acyl chain composition cholesterol concentration active compound concentration residual organic solvents and heavy metals active compound/phospholipid ratio proton or ion gradient before and after remote loading (2) Chemical... 

---