Membranes, unsaturated fatty acids

Prostaglandins Endogenous chemical mediators involved in inflammation derived from the cellular membrane unsaturated fatty acid arachidonic acid. 

The mechanism of carbon tetrachloride nephrotoxicity involves the initial homolytic cleavage of carbon tetrachloride by cytochrome P450 to form the trichloromethyl and chlorine free radicals (Figure 6). The trichloromethyl free radical can then alkylate renal macromolecules or interact with membrane unsaturated fatty acids to initiate lipid peroxidation. The trichloromethyl free radical may also combine with molecular oxygen to form a peroxy free radical that is more reactive than the trichloromethyl free... 

Jacques, N. A., Jacques, V. L., Wolf, A. C. Wittenberger, C. L. (1985). Does an increase in membrane unsaturated fatty acids account for Tween 80 stimulation of glucosyltransferase secretion by Streptococcus salivariusl J. Gen. Microbiol, 131, Fill. 

He/minthosporium (15). The mode of action is considered to be inhibition of the enzyme NADPH-cytochrome C reductase, which results in the generation of free radicals and/or peroxide derivatives of flavin which oxidize adjacent unsaturated fatty acids to dismpt membrane integrity (16) (see Enzyme inhibitors). 

The double bonds found in fatty acids are nearly always in the cis configuration. As shown in Figure 8.1, this causes a bend or kink in the fatty acid chain. This bend has very important consequences for the structure of biological membranes. Saturated fatty acid chains can pack closely together to form ordered, rigid arrays under certain conditions, but unsaturated fatty acids prevent such close packing and produce flexible, fluid aggregates. 

In addition to unsaturated fatty acids, several other modified fatty acids are found in nature. Microorganisms, for example, often contain branched-chain fatty acids, such as tuberculostearic acid (Figure 8.2). When these fatty acids are incorporated in membranes, the methyl group constitutes a local structural perturbation in a manner similar to the double bonds in unsaturated fatty acids (see Chapter 9). Some bacteria also synthesize fatty acids containing cyclic structures such as cyclopropane, cyclopropene, and even cyclopentane rings. 

Figure 41-3. Diagrammatic representation of a phospholipid or other membrane lipid. The polar head group is hydrophilic, and the hydrocarbon tails are hydrophobic or lipophilic. The fatty acids in the tails are saturated (S) or unsaturated (U) the former are usually attached to carbon 1 of glycerol and the latter to carbon 2. Note the kink in the tail of the unsaturated fatty acid (U), which is important in conferring increased membrane fluidity.

Figure 41-5. Diagram of a section of a bilayer membrane formed from phospholipid molecules. The unsaturated fatty acid tails are kinked and lead to more spacing between the polar head groups, hence to more room for movement. This in turn results in increased membrane fluidity. (Slightly modified and reproduced, with permission, from Stryer L Biochemistry, 2nd ed. Freeman, 1981.)...

It has been found that the catalytic activity of PKC is enhanced by a lipid component of the cell membrane, namely phosphatidylserine. This activity is further stimulated by sn-1,2-diacylglycerol. Oleic acid also activates the enzyme in the presence of 1,2-diacylglycerol, and thus it is presumed to mimic phosphatidylserine. In order to identify that modulating binding site for oleic acid on PKC, a photoaffinity analogue was devised. A carbene generating photophore, diazirine was placed in the apolar terminus of the unsaturated fatty acid ligand (30, Fig. 12). The synthesis and the photochemical activation properties were reported by Ruhmann and Wentrup [113]. 

It is commonly known that lipids, carbohydrates, and glycolipids are present in the Golgi apparatus (27). The determination of the components that react with the ZIO mixture was carried out by removing each component from tissues before incubation in the ZIO mixture. After lipid extraction by acetone (14), chloroform-methanol (15), or propylene oxide (27), no osmium-zinc precipitates could be detected in structures that normally reacted with ZIO. Blumcke et al. (15) summarized the nature of the lipids that react with the ZIO mixture as follows lipids and lipoproteins of cell membranes, neutral fat droplets (41), and lipid globules of type II pneumocytes and alveolar macrophages were, however, not as electron dense as the normally reactive lamellae containing highly unsaturated fatty acids. 

The daily output of fecal fat may be regarded as the simplest quantitative measure of the effect of gluten on these patients. The evidence available suggests that the extra fat is derived from dietary fat and mainly represents interference with absorption. There is usually a disproportionate increase of saturated as compared with unsaturated fats (W4). The reason for this is not clear. There may be selective rejection of longer chain and more saturated fats there may also be increased hydrogenation of unsaturated fatty acids (SI). The increase of fat output may occur within a day or 2, or it may be delayed for 10 days or more. There are many possible explanations for this delay. It may require many small insults to the mucous membrane... 

UV-induced ROS are extremely toxic to cells by causing oxidative damage to all biomolecules (Sies 1991). For instance, lipids, which are major compounds of all biological membranes, may be destroyed by ROS. After a first initiation reaction an unsaturated fatty acid is converted to a peroxyl radical, which in turn attacks another unsaturated fatty acid finally leading to free radical cascades. This photochemical peroxidation of unsaturated fatty acids may be particularly damaging for membrane structure and function (Bischof et al 2006a). 

Several different tocopherols are known to have vitamin E activity, but a-tocopherol, a trimethyltocol (Figure 12.9) is the most biologically active. Other less potent forms are the /3-, y- and S-tocopherols, which contain fewer methyl groups. They all have antioxidant properties and a deficiency results in a lack of protection of the unsaturated fatty acids in the membrane phospholipids against oxidation by molecular oxygen. 

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