Fatty acid in membrane phospholipids

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. 

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. 

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

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. 

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. 

Fig. 10.7 RNA synthesis in vesicles. Membrane permeability can be regulated by choosing the correct chain length of the fatty acids in the phospholipids. Short chains (a) make the bilayer so unstable that even large molecules such as proteases can enter the vesicle interior and damage the polymerase. Carbon chains which are too long (b) prevent the entry of substrate molecules such as ADR RNA polymerisation in the vesicle occurs only with C14 fatty acids (c)...

As shown in Table 1, the acyl moiety of cardiolipin is comprised almost entirely of unsaturated fatty acids. Other membrane phospholipids such as phosphatidyl choline and phosphatidyl ethanolamine contain 1(M0 mol of saturatedfatty acids such as palmitic acid (Ci6 0) and stearic acid (Ci8 0) per 100 mol of total fatty acids. In particular,linoleic acid (Cl8 2) is the most abundant polyunsaturated fatty acid consisting of 80 mol%, linolenic acid (Cl8 3) 8 mol%, and oleic acid (Ci8 i) 6 mol%. Therefore, by using a commercially available cardiolipin purified from bovine heart mitochondria, we characterized auto-oxidation products by reverse phase HPTLC and reverse phase HPLC. 

Chronic changes in the type of fat in the diet can change the type of polyunsaturated fatty acids in the phospholipids that are components of membranes and hence change fluidity of the membrane. This might change the activity of the phospholipase and/or the type of eicosanoid produced from... 

Cholesterol The pathway for synthesis of cholesterol is described in Appendix 11.9. Cholesterol is important in the structure of membranes since it can occupy the space that is available between the polyunsaturated fatty acids in the phospholipid (Chapter 4). In this position, cholesterol restricts movement of the fatty acids that are components of the phosphoglycerides and hence reduces membrane fluidity. Cholesterol can be synthesised de novo in proliferating cells but it can also be derived from uptake of LDL by the cells, which will depend on the presence of receptors for the relevant apoUpoproteins on the membranes of these cells (Appendix 11.3). 

Kitchen (1977) has analyzed the fatty acids in the phospholipids isolated from the MFGM, finding more unsaturated and less saturated acids than in the membrane TG. These findings are not unexpected. 

Because of their high lipid content, cell membranes are not permeable to highly polar substances and are fluid or "water bed-like" rather than firm or rigid. The relative fluidity is determined largely by the type and abundance of unsaturated fatty acids in the phospholipids. The greater the abundance of unsaturated fatty acids, and the greater the amount of unsaturation within the acids, the greater the fluidity of the membrane. 

In aerobic cells, polyunsaturated fatty acids of membrane phospholipids easily undergo such oxidative chain reactions [111,112]. This is because the double bonds of the polyunsaturated structure are repeatedly connected to each other by c/s-methylene units. Such bis-allylic structures enable electron delocalization on five carbon atoms, making the initial hydrogen abstraction on... 

As discussed in Section 3.7, when these phospholipids are mixed with water, they assemble in an arrangement called a lipid bilayer. The ionic heads of the phospholipid are oriented on the outside and the nonpolar tails on the inside. The identity of the fatty acids in the phospholipid determines the rigidity of this bilayer. When the fatty acids are saturated, they pack well in the interior of the lipid bilayer. and the membrane is quite rigid. When there are many unsaturated fatty acids, the nonpolar tails cannot pack as well and the bilayer is more fluid. Thus, important characteristics of this lipid bilayer are determined by the three-dimensional stmcture of the molecules that comprise it. 

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). 

The serum phospholipids and red cell membrane phospholipids of children with SCD have an altered fatty acid composition. We and others (2123) have shown that children with SCD have lower percentages of the long-chain n-3 PUFA and increased percentages of saturated fatty acids in their phospholipids. In addition, Connor and co-workers (22) documented that the red cell membrane phospholipids of children with SCD have a higher proportion of saturated and monounsaturated fatty acids and a lower proportion of PUFA in the sn-2 position. This abnormality in fatty acid content can be reversed by supplementation with PUFA, as demonstrated by Muskeit and co-workers (23) who found an increase in the level of n-3 fatty acids in both plasma cholesterol esters and red blood cell phospholipids of children with SCD after supplementation with fish oil. 

Membrane flexibility is increased when the proportion of unsaturated hydrocarbon chains is increased. The presence of some cis- rather than trans- polyunsaturated fatty acids in the phospholipid hydrocarbon chain is believed to be necessary to optimise efficient lateral packing and ensure fluidity. 

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