Fatty acids membrane phospholipid

Arachidonic acid is present in membranes and accounts for 5-15% of the fatty acids in phospholipids. Docosahexaenoic acid (DHA 0)3, 22 6), which is syn-... 

Corsico, B., Cistola, D.P., Frieden, C. and Storch, J. (1998) The helical domain of intestinal fatty acid binding protein is critical for collisional transfer of fatty acids to phospholipid membranes. Proceedings of the National Academy of Sciences USA 95,12174-12178. 

Trans fatty acids The phospholipids in the plasma and in membranes of all cells contain long-chain polynnsatnrated fatty acids (PUFA). During periods of growth and development of organs, PUFAs are reqnired for phospholipid synthesis. The PUFAs are, of conrse, obtained from dietary triacylglycerol and phospholipids. The donble bonds in most natural fatty acids are cis not trans Nonetheless trans fatty acids do occur in dietary fats. If the diet contains trans fatty acids, they might be incorporated into the phospholipids along with the cis fatty acids and hence into membranes. The presence of these abnormal fatty acids will modify the stmctnre of the phospholipids which conld impair the fnnction of the membrane. There are two main sonrces of trans fatty acids in the diet foods produced from ruminants contain trans fatty... 

Comparison between DNA repair and phospholipid repair The processes that can lead to DNA damage and the type of damage are described in Chapter 9 and Appendix 9.6. The repair processes involve removal of the specific nucleotide(s) by an exonuclease and replacement of the nucleotide by a DNA polymerase. Since the strand must be broken to remove the damage (by an endonuclease) these parts of the strand must be repaired by a ligase. The process is known as excision-repair. Of interest, there is a degree of similarity between the removal of damaged polyunsaturated fatty acids from phospholipids in membranes and replacement with a new fatty acid by two enzymes, a deacylase and an acyltransferase (see above and Chapter 11), and excision-repair of DNA. 

Fig. 4.14 An example of a reaction of fatty acid with phospholipid that results in the destruction of cell membrane...

Fig. 3. Autoxidation of polyunsaturated fatty acids in phospholipid membranes. Addition of oxygen to lipid free radicals is extremely fast. It yields peroxyl radicals ROO which will tend to capture labile hydrogen atoms of neighbouring polyunsaturated lipids. Accidentally produced free radicals will therefore initiate a chain reaction of lipid peroxidation which will propagate along membranes. This process can result in several dozen propagation steps before it is stopped by a termination reaction. Examples of such termination reactions are the recombination of peroxyl radicals and the formation of a stable free radical from a free radical scavenger (scavH). Termination through recombination of low steady-state concentration of alkyl radicals is unlikely in aerobic medium.

Free radicals may also be formed by (a) homolysis of covalent bonds, (b) addition of an electron to a neutral atom, or (c) loss of a single electron from a neutral atom. These radicals, especially if they are of low molecular weight, are usually extremely reactive hence, they are short-lived. Since they have an unpaired electron, they are highly electrophilic (i.e., electron loving ) and attack sites of increased electron density, as in compounds with nitrogen atoms (e.g., proteins, amino acids, DNA, RNA) and carbon-carbon double bonds (i.e., polyuunsaturated fatty acids and phospholipids which make up bilipid cell membranes). 

Most of these effects of vitamin E deficiency can be attributed to membrane damage. In deficiency, there is an accumulation of lysophosphatidylcholine in membranes, which is cytolytic. The accumulation of lysophosphatidylcholine is a result of increased activity of phospholipase A. It is not clear whether a-tocopherol inhibits phospholipase A whether there is increased phospholipase activity because of increased peroxidation of polyunsaturated fatty acids in phospholipids, and hence an attempt at membrane Upid repair or whether the physicochemical effects of a-tocopherol on membrane organization and fluidity prevent the cytolytic actions of lysophosphatidylcholine (Douglas et al., 1986 Erin et al., 1986). 

Ortiz, A. and Gomez-Femandez, J. C. A Differential scanning calorimetry study of the interaction of free fatty acids with phospholipid membranes. Chemistry and Physics of Lipids 45 75-9, 1987. 

There is a solvent-related pH dependence that varies with the specific reaction components and conditions (e.g., liposomes vs. membranes vs. emulsions, fatty acids vs. phospholipids, buffer type, heme compound). 

The accumulation of cyclopropane fatty acid-containing phospholipids is promoted in bacteria by low pH and low p02, conditions which attend entrance into stationary phase cultures. The conversion of olefin to cyclopropane alters membrane fluidity and probably other functional parameters as well and may be a physiological response to altered environmental conditions. 

V.Z. Lankin, Yu.G. Osis and A.K. Tikhaze, Hydroperoxy- and hydroxy-derivatives of free fatty acids and phospholipids as modifiers of liposomal membrane structure, Dokl.Akad.Nauk 351 (1996) 269-271 (English translation in Doklady Biochemistry). 

Phospholipid synthesis occurs in the membrane of the SER. After phospholipids are synthesized, they are remodeled by altering their fatty acid composition. Phospholipid degradation is catalyzed by several phospholipases. 

Edge, R., Land, E.J., McGarvey, D., Mulroy, L., and Truscott, T.G. (1998) Relative one-electron reduction potentials of carotenoid radical cations and the interactions of carotenoids with the vitamin E radical cation, J. Am. Chem. Soc., 120, 4087 4090. Fleschner, C.R. (1995) Fatty acid composition of triacylglycerols, free fatty acid and phospholipids from bovine lens membrane fractions, Invest. Ophthal. Vis. Sci., 36, 261-264. Fraunfelder, F.T. (1982) Drug-Induced Ocular Side Effects and Drug Interactions, 2nd ed., Philadelphia Lea Febiger. 

Fig. 10. Coordinate regulation of fatty acid and phospholipid metabolism. The pleiotropic regulator ppGpp regulates transfer of fatty acids to the membrane via inhibition of the PlsB acyltransferase step, coordinating phospholipid synthesis with macromolecular synttesis. PlsB inhibition leads to the accumulation of long-chain acyl-ACPs that feedback inhibit their own synthesis at the point of initiation (inhibition of acetyl-CoA carboxylase and FabH) and elongation, by inhibition of Fabl. LPA, lysophosphatidic acid G3P, glycerol-3-phosphate.

Experiments carried out with Mucor mucedo (mildew) show that Terrazole inhibits, at the cellular level, the synthesis of triglycerides and sterol esters, stimulates that of free fatty acids and phospholipids,480 but does not appreciably affect nucleic add synthesis.481 Phospholipase is released in cell membranes and mitochondria the associated reduction in mitochondrial... 

It is generally accepted that Ca + mobilization is crucial for the activation of phospholipases. However, Sevanian and coworkers (Sevanian et al., 1981 Sevanian and Kim, 1985) demonstrated that phospholipase A2 can also be activated in the absence of elevated Ca + by the presence of peroxi-dized fatty acids in phospholipids. The degree of phospholipase activation was correlated with the extent of TBARS. Thus, both peroxidized fatty acids and Ca + can independently trigger degradation of membrane lipids, but may also act syner-... 

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