Phospholipids and cell membranes

Phospholipids and Cell Membranes 1050 THE CHEMISTRY OF... STEALTH Liposomes for Drug Delivery 1053... 

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. 

Lyotropic liquid-crystalline nanostructures are abundant in living systems. Accordingly, lyotropic LC have been of much interest in such fields as biomimetic chemistry. In fact, biological membranes and cell membranes are a form of LC. Their constituent rod-like molecules (e.g., phospholipids) are organized perpendicularly to the membrane surface yet, the membrane is fluid and elastic. The constituent molecules can flow in plane quite easily but tend not to leave the membrane, and can flip from one side of the membrane to the other with some difficulty. These LC membrane phases can also host important proteins such as receptors freely floating inside, or partly outside, the membrane. 

In the human body choline is needed for the synthesis of phospholipids in cell membranes, methyl metabolism, transmembrane signaling and lipid cholesterol transport and metabolism [169]. It is transported into mammalian cells by a high-affinity sodium-dependent transport system. Intracellular choline is metabolized to phosphorylcholine, the reaction being catalyzed by the enzyme choline... 

Nonreceptor-Mediated Drug Action. At least one important class of drugs, the general anesthetics, has been assumed not to owe its therapeutic activities to a specific receptor process. Anesthetic potency shows an excellent linear correlation with partition coefficient and this has been extrapolated to a definition of action at a lipid site. The phospholipids of cell membranes, particularly nerve cells, have been considered as principal targets for general anesthetic action. It has been hypothesized... 

Arachidonic acid (5,8,11,14-eicosatetraenoic acid), a polyunsaturated fatty acid derived from dietary sources or by desaturation and chain elongation of the essential fatty acid linoleic acid, is found widely in the body. It is transported in a protein-bound state and stored in the phospholipids of cell membranes in all tissues of the body [108] from where it can be changed into biologically... 

Either of two solutions can be used to redissolve the radiolabeled sterols. The first, oil, is simpler to prepare and administer to the mice. However, it is not strictly a physiological representation of dietary cholesterol, which is largely present with phospholipids in cell membranes, and the oikcholesterol ratio is much greater than would occur in most diets. The second solution, a lipid emulsion, is more tedious to prepare and is less stable but is more physiologically accurate. 

Since polyunsaturated fats are present in substantial amounts in the phospholipids of cell membranes, and since cellular proliferation requires formation of new membranes, this might explain the requirement for polyunsaturated fatty acids in tumor promotion, but there are also other possibilities. For example, there is evidence that cell-mediated immune responses are inhibited by linoleic acid, and reduced responsiveness of the immune system could help to promote tumorigenesis (23). 

The EFA stored in the phospholipids of cell membranes are released by phospholipases, and then undergo oxidative transformation by the cyclooxygenase (COX) pathway to prostanoids and by the lipoxygenase pathway to hydroxy fatty acids and leukotrienes. The metabolism to prostanoids is catalyzed by two isoenzymes of COX, a constitutive (COX-1) and an inducible form (COX-2). The main products of COX metabolism of AA are prostaglandin E2 (PGE2), PGI A, and PGD2. In addition, A A is converted via 15-lipoxygenase to 15-hydroxyeicosatetraenoic acid (15-HETE) and lipoxins, by... 

Arachidonic acid, a 20-carbon fatty acid, is the primary precursor of the prostaglandins and related compounds (see Figure 39.3). Arachidonic acid is present as a component of the phospholipids of cell membranes, primarily phosphatidyl inositol and other complex lipids.1 Free arachidonic acid is released from tissue phospholipids by the action of phospholipase A2 and other acyl hydrolases, via a process controlled by hormones and other stimuli (see Figure 39.3). There are two major pathways in the synthesis of the eicosanoids from arachidonic acid (see Figure 39.3). 

Szejtli, J., Cserhati,T., and Szogyi, M. (1986), Interactions between cyclodextrins and cell-membrane phospholipids, Carbohydr. Polym., 6, 35 19. 

Thus far, the interactions of phospholipid head groups have been considered, because the model was applied toward rationalizing the membranolysis of eukaryotic cells such as erythrocytes, and PLs are the primary constituents of eukaryotic cell membranes. A reasonable question to ask at this time is whether the above results are relevant to prokaryotic membranes. Although PLs constitute a smaller proportion of the prokaryotic cell wall and cell membrane, the other constituent molecules such as liopolysaccharides and teichoic acids, are also amphiphilic. The general structure of a hydrophilic portion attached to a hydrophobic tail is common... 

Choline is an essential component of phospholipids - phosphatidylcholine (lecithin) is the major phospholipid in cell membranes and sphingomyelin is important in the nervous system. Acetylcholine is a transmitter in the central and parasympathetic nervous systems and at neuromuscular junctions, and has a role in the regulation of differentiation and development of the nervous system (Biagioni et al., 2000). Acetylcholine is also synthesized in mononuclear lymphocytes, where it has an autocrine or paracrine role in regulating immune function (Fujii and Kawashima, 2001). 

The ceils of mammals and other animals contain the following structures. A plasma membrane (FM), which is the outer border of the cell, has a structure similar to the bilayer sheet shown in Figure 1.12. The PM contains phospholipids and many membrane-bound (embedded) proteins used to facilitate the transport of nutrients and minerals into and out of the cell, The outside of the FM of some cells is coated with polysaccharides for protection. The outside of the PM of other cells bears proteins that control which cells are chosen neighbors. Generally, the material bound to the outside of the PM is synthesized by the cel itself rather than derived from other cells. The cytoplasm is the fluid contained and bounded by the plasma membrane. This fluid has a gel-like consistency because it contains a high concentration of proteins. Most of the biochemical reactions that occur within the cell take place in the cytoplasm. The remainder take place within various organelles. 

PhosphattdykhoHne (PC) and phosphatidylethanolamine (PE) are the major phospholipids of cell membranes. Table 6.1 lists the amount of lipid in cell membranes expressed as micrograms of lipid per milligram of membrane-bound protein. The membranes were isolated from cells of adipose tissue from rats that had been raised on a diet containing sunflower oil (100 g oil/kg diet) as the source of lipids. The diet was essentially free of cholesterol and phospholipids because plants do not contain cholesterol and the phospholipids of vegetable oils are removed during the refining process. 

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