Fatty acids in membranes

The role of essential fatty acids in membrane formation is unrelated to prostaglandin formation. Prostaglandins do not reheve symptoms of essential fatty acid deficiency, and an essential fatty acid deficiency is not caused by inhibition of prostaglandin synthesis. 

Figure 45-6. Interaction and synergism between antioxidant systems operating in the lipid phase (membranes) of the cell and the aqueous phase (cytosol). (R-,free radical PUFA-00-, peroxyl free radical of polyunsaturated fatty acid in membrane phospholipid PUFA-OOH, hydroperoxy polyunsaturated fatty acid in membrane phospholipid released as hydroperoxy free fatty acid into cytosol by the action of phospholipase Aj PUFA-OH, hydroxy polyunsaturated fatty acid TocOH, vitamin E (a-tocopherol) TocO, free radical of a-tocopherol Se, selenium GSH, reduced glutathione GS-SG, oxidized glutathione, which is returned to the reduced state after reaction with NADPH catalyzed by glutathione reductase PUFA-H, polyunsaturated fatty acid.)...

It is the damage to DNA in the epithelial cells of the skin that is usually considered to be the cause of the development of melanoma due to excessive exposure to sunlight (Chapter 21). However, an alternative or additional mechanism could be the damage to polyunsaturated fatty acids in membrane phospholipid in the epithelial cells. This could be due, as in the case of DNA damage, to the local production of free radicals (Appendix 9.6). The damaged polyunsaturated fatty acids (e.g. peroxidised or hydroperoxide fatty acids) will disrupt the membrane which might facilitate the binding of key proteins of proliferation to these membranes or result in the production of abnormal eicosanoids either of which could facilitate inappropriate proliferation. 

Kayser, S. G. and Patton, S. 1970. The function of very long chain fatty acids in membrane structure Evidence from milk cerebrosides. Biochem. Biophy. Res. Commun. 41, 1572-1578. 

For this purpose liposomes are used as lipid phase. Unilamellar liposomes are artificial lipid bilayer vesicles. They can be considered as real model bilayer membranes as they ideally consist of a circular bilayer membrane. The hydrophobic acyl chains are assembled in the hydrophobic core of the liposome whereas the hydrophilic head groups point to the water in the inside and outside of the vesicle. Liposomes can be produced from a variety of lipids and from mixtures of lipids. This possibility allows studying the influence of membrane constituents on the partition of solutes. Kramer et al. (1997) studied the influence of the presence of free fatty acids in membranes on the partition behaviour of propranolol. The influence on a-Tocopherol in membranes on the partition behaviour of desipramine has been reported recently (Marenchino et al. 2004) using a liposome model. 

The main effect of riboflavin deficiency is on lipid metabolism. In experimental animals on a riboflavin-free diet, feeding a high-fat diet leads to more marked impairment of growth, and a higher requirement for riboflavin to restore growth. There are also changes in the patterns of long-chain polyunsaturated fatty acids in membrane phospholipids. 

Combos Z, Wada H, Murata N. Unsaturation of fatty acids in membrane lipids enhances tolerance of Cyanobacterium synechocystis 42. PCC6803 to low-temperature photoinhibition. Proc. Natl. Acad. 

ROS then cause peroxidation of polyunsaturated fatty acids in membrane phospholipids. 

Stillwell W, Ehringer WD, Wassail SR. Interaction of a-tocopherol with fatty acids in membranes and ethanol. Biochim Biophys Acta 1992 1105 237-244. 

By feeding nutritionally adequate diets, dietary intake of 18 2n-6, 18 3n-3, or the proportion of 18 2n-6 to 18 3n-3, particularly during development, has been shown to influence the content of long-chain polyunsaturated fatty acids in membrane lipids by changing the composition of the whole brain, oligodendrocytes, myelin, astrocytes mitochondrial, microsomal, and synaptosomal membrane (Bourre et al., 1984 Foot et al., 1982 Lamptey Walker, 1976 Tahin et al., 1981). Feeding diets with a 18 2n-6 to 18 3n-3 fatty acid ratio between 4 1 and 7 1 to rats from birth to 1, 2, 3, and 6 wk of... 

There is one very important feature of the type II system that should not be overlooked. Although a hard-wired type I mechanism may seem more efficient, it only produces a single product. In contrast, the type II system is not only responsible for producing all the diversity of fatty acids in membranes, the intermediates of the pathway are diverted for the synthesis of other key molecules. These include biotin, lipoic acid, and the quorum-sensing... 

Vitamin E - also called ot-tocopherol. Vitamin E is an antioxidant. It is particularly effective in preventing the attack of peroxides on unsatured fatty acids in membrane lipids. Deficiency of vitamin E also leads to other symptoms, however, so vitamin E probably plays other roles as yet undiscovered. 

Hydroxyl Radical - Hydroxyl radical damages proteins, nucleic acids, and the fatty acids in membrane lipids (lipid peroxidation). Lipid peroxidation occurs as a chain reaction. 

Glycerides consist of glycerin, an alcohol from the C< pool, which is esterified with three fatty acids (Fig. 8) to form flits as an energy store. In phospholipids one fatty acid is replaced by phosphoric acid. Phospholipids form membranes that isolate the inner part of cells from the surrounding environment because of their arrangement as a bilayer. The hydrophobic alkyl chains of the fatty acids are directed toward the inner side of the bilayer and the hydrophilic phosphate ends form the surface of the membrane. Membranes are most important for cellular function and therefore are part of all organisms. The composition of fatty acids in membranes is specific to source organisms and hence is used to describe microbial community structures (Olsson, 1999). 

Millar, A.A., Wrischer, M., and Kunst, L. Accumulation of very-long-chain fatty acids in membrane glycerolipids is associated with dramatic alterations in plant morphology. Plant Cell 10, 1889-1902, 1998. 

How does the composition of the bilayer affect its properties The presence of unsaturated fatty acids in membrane components leads to greater fluidity than with a preponderance of saturated fatty acids. Lateral motion of lipid molecules within one layer of a membrane occurs frequently. 

The higher percentage of unsaturated fatty acids in membranes in cold climates is an aid to membrane fluidity. 

Polyunsaturated fatty acids affect the fluidity of membranes, thereby affecting cell membrane functions. On the other hand, increasing the proportions of saturated and monounsaturated fatty acids in membrane phospholipids decreases fluidity. In this study, we observed a positive correlation between phase angle and all of the n-3 PUFA but an inverse correlation between phase angle and palmitate and oleic acid. These results suggest that the phase angle may reflect some property of cell membranes that is related to fluidity. 

The incorporation of unsaturated fatty acids into membrane lipids of human and animal tissue may also be affected by other dietary factors. One of them is chronic exposure to ethanol [439-442]. Ethanol can decrease the amounts of the w6 series of essential fatty acids in membrane lipids and can markedly lower the ratio of C20 4w6/Ci8 2u,6- Thesc changes have been attributed to a decreased absorption and/or an increased utilization of essential fatty acids and to inhibition of the 4 -desaturase enzyme by chronic intake of ethanol [443,444]. 

As mentioned before, singlet oxygen ( o ) is a reactive species that reacts with molecules, such as vitamin E, vitamin C, DNA, cholesterol, carotenoids, polyunsatmated fatty acids in membranes, and certain amino acids. 

Song, J.H. and Miyazawa, T., Enhanced level of n-3 fatty acid in membrane phospholipids induces lipid peroxidation in rats fed dietary docosahexaenoic acid oil. Atherosclerosis, 155, 9-18, 2001. 

---