Polyunsaturated membrane lipids

Lipid peroxidation is a special form of autoxidation, where the primary target molecules are polyunsaturated fatty acids and their derivatives [15]. These compounds are more susceptible to peroxidation than cholesterol due to the presence of double-allylic hydrogens, which are easily extracted as a result of stabilization of the radical formed. Cholesterol, a major component in cell membranes together with the polyunsaturated membrane lipids, becomes a second target of the radical chain reaction leading to the formation of compounds 1-8 [15]. 

Several strategies have been developed to characterise the structural and functional role of particular molecular species of membrane lipid. The use of phospholipid exchange or transfer proteins have been described to exchange one molecular species of a lipid class for another or enrich membranes in specific molecular species, respectivly. Another method has been to hydrogenate the double bonds of polyunsaturated membrane lipids in situ using homogeneous catalysts and to study the consequences of lipid saturation on membrane functions [2]. With the isolation of mutant strains of Arabidopsis defective in desaturation of chloroplast fatty acids [3,4] the question can be addressed directly without the problems associated with the use of exchange or transfer proteins or introduction of transition metal catalysts. 

Free arachidonic acid, along with diacylglycerols and free docosahexaenoic acid, is a product of membrane lipid breakdown at the onset of cerebral ischemia, seizures and other forms of brain trauma. Because polyunsaturated fatty acids are the predominant FFA pool components that accumulate under these conditions, this further supports the notion that fatty acids released from the C2 position of membrane phospholipids are major contributors to the FFA pool, implicating PLA2 activation as the critical step in FFA release [1,2] (Fig. 33-6). 

The extent of membrane lipid polyunsaturation is another modulator of cellular oxidative susceptibility an example is mentioned above in the NO section. This is not surprising, and it has a chemical rationale since the sites of attack of oxidizing free radical species in lipids are the double bonds in polyunsaturated phospholipid stmctures in membranes. Therefore, it follows. 

This cascade however may be propagated throughout the cell unless terminated by a protective mechanism (see below) or a chemical reaction such as disproportionation, which gives rise to a non-radical product. Polyunsaturated fatty acids, found particularly in membranes, are especially susceptible to free radical attack. The effects of lipid peroxidation are many and various. Clearly, the structural integrity of membrane lipids will be adversely affected. In the lipid radical produced, the sites of unsaturation may change, thereby altering the fluidity of the membrane (see chap. 3). Lipid radicals may interact with other lipids and... 

Fatty acid chains may contain no double bonds—that is, be satu rated, or contain one or more double bonds—that is, be mono- or polyunsaturated. When double bonds are present, they are nearly always in the cis rather than in the trans configuration. (See p. 362 for a discussion of the dietary occurrence of cis and trans unsatu- rated fatty acids.) The introduction of a cis double bond causes the I tfatty acid to bend or "kink" at that position (Figure 16.3). If the fatly acid has two or more double bonds, they are always spaced at three carbon intervals. [Note In general, addition of double bonds decreases the melting temperature (Tm) of a fatty acid, whereas j increasing the chain length increases the Tm. Because membrane lipids typically contain LCFA, the presence of double bonds in some fatty acids helps maintain the fluid nature of those lipids.]... 

Membrane lipids in brain contain high levels of polyunsaturated fatty acid side chains that are prone to free radical attack. 

HYDROXYL RADICAL (.Oil) CAN READILY OXIDIZE 1) MEMBRANE LIPIDS CONTAINING POLYUNSATURATED FATTY ACIDS, 2) NUCLEIC ACIDS AND 3) SULFIIYDRYL GROUPS OF PROTEINS. 

The potential consequences of the peroxidation of membrane lipids include loss of polyunsaturated fatty acids, decreased lipid fluidity, altered membrane permeability, effects on membrane-associated enzymes, altered ion transport, release of material from subcellular compartments, and the generation of cytotoxic metabolites of lipid hydroperoxides. The physiological significance of lipid peroxidation products is shown in Table 1. 

Pyridoxal phosphate has a clear role in lipid metabolism as the coenzyme for the decarboxylation of phosphatidylserine, leading to the formation of phosphatidylethanolamine, and then phosphatidylcholine (Section 14.2.1), and membrane lipids from vitamin Bg-deficient animals are low in phosphatidylcholine (She et al., 1995). It also has a role, less well defined, in the metabolism of polyunsaturated fatty acids vitamin Bg deficiency results in reduced activity of A desaturase and impairs the synthesis of eicosapentanoic and docosahexanoic acids (Tsuge et al., 2000). 

Most of these effects of vitamin E deficiency can be attributed to membrane damage. In deficiency, there is em accumulation of lysophosphatidylcholine in membranes, which is cytolytic. The accumulation of lysophosphatidylcholine is a result of increeised 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, emd hence an attempt at membrane lipid repair or whether the physicochemiced effects of a-tocopherol on membrane organization and fluidity prevent the cytolytic actions of lysophosphatidylcholine (Douglas et ed., 1986 Erin et al., 1986). 

Popp-Snigders C, Shouten JA, Van Blitterswijck WJ, Van der Veen EA. Changes in membrane lipid composition of human erythrocytes after dietary supplementation of (n-3) polyunsaturated fatty acids. Biochim Biophys Acta 1986 854 31-37. 

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... 

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