Mechanism phospholipids

Choline, a component of the phospholipids in cell membranes, can be prepared by Sn2 reaction of trimethylamine with ethylene oxide. Show the structure of choline, and propose a mechanism for the reaction. 

Florio, V. A., and Stemweis, P. C. (1989). Mechanism of muscarinic receptor action on G0 in reconstituted phospholipid vesicles. J. Biol. Chem. 264 3909-3915. 

PLTP is responsible for the majority of phospholipid transfer activity in human plasma. Specifically, it transfers surface phospholipids from VLDL to HDL upon lipolysis of triglycerides present in VLDL. The exact mechanism by which PLTP exerts its activity is yet unknown. The best indications for an important role in lipid metabolism have been gained from knockout experiments in mice, which show severe reduction of plasma levels of HDL-C and apoA-I. This is most likely the result of increased catabolism of HDL particles that are small in size as a result of phospholipid depletion. In addition to the maintenance of normal plasma HDL-C and apoA-I concentration, PLTP is also involved in a process called HDL conversion. Shortly summarized, this cascade of processes leads to fusion of HDL... 

A molecular variation of plasma membrane has been reported by Puccia et al. Reduction of total lipids (XL) content and significant variations of triglyceride (TG) and phospholipids (PL) fractions were observed as a consequence of exposure of C. intestinalis ovaries to TBTCl solutions. In particular, an evident TG decrease and a PL increase were observed, which probably provoked an increment in membrane fluidity, because of the high concentration of long chain fatty acids and, as a consequence, PL. This could be a cell-adaptive standing mechanism toward the pollutants, as observed in Saccharomyces cerevisiae. Also the increase in the content of the polyunsaturated fatty acids (PUPA), important in the synthesis of compounds such as prostaglandin which are present in the ovary in a stress situation, was probably a consequence of a defense mechanism to the stress provoked by the presence of TBTCl. 

The second type of fatty liver is usually due to a metabolic block in the production of plasma lipoproteins, thus allowing triacylglycerol to accumulate. Theoretically, the lesion may be due to (1) a block in apolipoprotein synthesis, (2) a block in the synthesis of the lipoprotein from lipid and apolipoprotein, (3) a failure in provision of phospholipids that are found in lipoproteins, or (4) a failure in the secretory mechanism itself. 

The mechanisms involved in the establishment of lipid asymmetry are not well understood. The enzymes involved in the synthesis of phospholipids are located on the cytoplasmic side of microsomal membrane vesicles. Translocases (flippases) exist that transfer certain phospholipids (eg, phosphatidylcholine) from the inner to the outer leaflet. Specific proteins that preferentially bind individual phospholipids also appear to be... 

Angiotensin II binds to specific adrenal cortex glomerulosa cell receptors. The hormone-receptor interaction does not activate adenylyl cyclase, and cAMP does not appear to mediate the action of this hormone. The actions of angiotensin II, which are to stimulate the conversion of cholesterol to pregnenolone and of corticosterone to 18-hydroxycorticosterone and aldosterone, may involve changes in the concentration of intracellular calcium and of phospholipid metabolites by mechanisms similar to those described in Chapter 43. 

Modeling Pardaxin Channel. The remarkable switching of conformation in the presence of detergents or phospholipid vesicles (5) suggests that pardaxin is a very flexible molecule. This property helps to explain the apparent ability of pardaxin to insert into phospholipid bilayers. In addition, it is consistent with the suggestion that the deoxycholate-like aminoglycosteroids (5,7) present in the natural secretion from which pardaxin is purified (5) serve to stabilize its dissociated conformation. The question of the mechanism by which pardaxin assembles within membranes is important for understanding pore formation and its cytolytic activity (5). 

The cell walls of mycobacteria contain three structures peptidoglycan, an arabinogalactan polysaccharide and long chain hydroxy fatty acids (mycolic acids) which are all covalently linked. Additional non-covalently attached lipid components found in the wall include glycolipids, various phospholipids and waxes. The lipid-rich nature of the mycobacterial wall is responsible for the characteristic acid-fastness on staining and serves as a penetration barrier to many antibiotics. Isoniazid and ethambutol have long been known as specific antimycobacterial agents but their mechanisms of action have only recently become more clearly understood. 

Liposomes — These are synthetic lipid vesicles consisting of one or more phospholipid bilayers they resemble cell membranes and can incorporate various active molecules. Liposomes are spherical, range in size from 0.1 to 500 pm, and are thermodynamically unstable. They are built from hydrated thin lipid films that become fluid and form spontaneously multilameUar vesicles (MLVs). Using soni-cation, freeze-thaw cycles, or mechanical energy (extrusion), MLVs are converted to small unilamellar vesicles (SUVs) with diameters in the range of 15 to 50 nm. ... 

Two principal routes of passive diffusion are recognized transcellular (la —> lb —> lc in Fig. 2.7) and paracellular (2a > 2b > 2c). Lateral exchange of phospholipid components of the inner leaflet of the epithelial bilayer seems possible, mixing simple lipids between the apical and basolateral side. However, whether the membrane lipids in the outer leaflet can diffuse across the tight junction is a point of controversy, and there may be some evidence in favor of it (for some lipids) [63]. In this book, a third passive mechanism, based on lateral diffusion of drug molecules in the outer leaflet of the bilayer (3a > 3b > 3c), wih be hypothesized as a possible mode of transport for polar or charged amphiphilic molecules. 

Figure 7.22b shows that hydrophilic molecules, those with log Kj < 1, are much more permeable in octanol than in olive oil. The same may be said in comparison to 2% DOPC and dodecane. Octanol appears to enhance the permeability of hydrophilic molecules, compared to that of DOPC, dodecane, and olive oil. This is dramatically evident in Fig. 7.7, and is confirmed in Figs. 7.8c and 7.22b. The mechanism is not precisely known, but it is reasonable to suspect a shuttle service may be provided by the water clusters in octanol-based PAMPA (perhaps like an inverted micelle equivalent of endocytosis). Thus, it appears that charged molecules can be substantially permeable in the octanol PAMPA. However, do charged molecules permeate phospholipid bilayers to any appreciable extent We will return to this question later, and will cite evidence at least for a partial answer. 

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