Oxidized phospholipids chemical structures

Megli and Sabatini [55] studied the phospholipid bilayers after lipoperoxidation. Phospholipids were oxidized, and the oxidized phospholipid species were separated by PLC and estimated by EPR. It was shown that the early stages of lipoperoxidation brought about disordering of the phospholipid bilayer interior rather than fluidity alterations and that prolonged oxidation may result in a loss of structural and chemical properties of the bilayer until the structure no longer holds. 

Fig. 13.1 Chemical structures of oxidized phospholipids. (A) Free radical-induced oxidation of l-palmitoyl-2-arachidonoyl-jn-glycero-3-phosphocholine (PA-PC) leads to a plethora of different oxidation products such as peroxidized phospholipids (not shown), truncated phospholipids, isoprostanes, isolevuglandins, and isothromboxanes.

It has already been emphasized that apoptotic cells can be both, the source of oxidized phospholipids as well as the initiators of apoptosis. Oxidation of (poly)-unsaturated phospholipids leads to a large variety of oxidation products (see Chapter 1 and (Fruhwirth et al., 2007)). These compounds may have very different chemical structures. It can be anticipated that they exert very different physical effects in membranes and undergo specific interactions with their target proteins and lipids. As a consequence, the great variety of oxidized phospholipids should be reflected by a corresponding diversity of biological effects. In many studies investigating cell survival and/or cell death, the effects of oxidized lipid... 

In recent years most studies on oxidized phospholipids have been performed using mixtures of oxidation products that are generated from their polyunsaturated parent compounds like PA-PC or oxidized lipoprotein particles (e.g. oxLDL). These preparations contain a large variety of different substances differing in structure, polarity and hydrophobicity as well as bioavailability. In many of these oxidized lipid preparations, neither the type nor the content of the individual oxidized components was known. Therefore, the respective compounds contribute to the apparent biological activities of oxidized lipid mixtures to a different and unpredictable extent. Thus, it will be desirable to concentrate on chemically defined lipid species in the future. 

Furthermore, it is mandatory to specify and standardize the solubilization of oxidized phospholipids for incubation with cells or individual target molecules. Physiologically relevant systems are pure lipid micelles or vesicles depending on the chemical structure of the lipid, complexes with proteins (e.g. albumin) and plasma lipoproteins. Furthermore, it has to be taken into account that oxidized phospholipids exchange between lipid surfaces much faster than regular membrane phospholipids containing two long hydrophobic acyl chains (Li et al.,... 

FIGURE 10.1 Chemical structures of typical OxPCs generated by peroxidation of paknitoyl-arachidonoyl-phosphatidylcholine. The figure presents a few most common molecular species selected from dozens of molecular species produced by nonenzymatic oxidation of a single precursor phospholipid. Note that oxidation can either add oxy functions to the full-size carbon chain or induce chain fragmentation. Both types of modifications produce phospholipids with abnormal properties and biological activities that were not characteristic of unoxidized phospholipid precursors. 

Fig. 2. Chemical structures of a typical phospholipid (phosphatidylcholine), a glycolipid (galactocerebroside), and two vesicle-forming block copolymers, poly(butadiene-6-ethylene oxide) and poly(styrene-6-acrylic acid.) The grey region indicates the hydrophobic interior of the bilayer.

Membranes, which are the subject of this section, can be relatively thick (0.1 mm) if made chemically (see their use in the PEM fuel cell, (Section 13.7.3). Biological membranes are very much thinner (50-100 A), of the same (3-5 nm) range as that of passive oxides (Section 12.5). Of what do biological membranes consist Figure 14.6 shows the essential constituents. They are lipids and proteins. How much there is of one and how much of the other varies widely. Thus, in a myelin membrane the lipid content is 80% while at the other end of the range, in mitochondria, there is an inner membrane containing only about 20% lipid. There are many kinds of lipids (as well as very many kinds of proteins), but those in membranes are usually phospholipids and are represented in Fig. 14.7. The structure often contains an H atom and this allows... 

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 structures in membranes. Therefore, it follows,... 

Niosomes In order to circumvent some of the limitations encountered with liposomes, such as their chemical instability, the cost and purity of the natural phospholipids, and oxidative degradation of the phospholipids, niosomes have been developed. Niosomes are nonionic surfactant vesicles which exhibit the same bilay-ered structures as liposomes. Their advantages over liposomes include improved chemical stability and low production costs. Moreover, niosomes are biocompatible, biodegradable, and nonimmunogenic [215], They were also shown to increase the ocular bioavailability of hydrophilic drugs significantly more than liposomes. This is due to the fact that the surfactants in the niosomes act as penetrations enhancers and remove the mucous layer from the ocular surface [209]. 

Application of data obtained from simple clean reaction systems in biological or chemical studies of heme catalysis also has its problems. Chemical model systems use chelators, model hemes, and substrate structures that are quite different from those existing in foods. Reaction sequences change with heme, substrate, solvent, and reaction conditions. Intermediates are often difficult to detect (141), and derivations of mechanisms by measuring products and product distributions downstream can lead to erroneous or incomplete conclusions. It is no surprise, then, that there remains considerable controversy over heme catalysis mechanisms. Furthermore, mechanisms determined in these defined model systems with reaction times of seconds to minutes may or may not be relevant to lipid oxidation being measured in the complex matrices of foods stored for days or weeks under conditions where phospholipids, fatty acid composition, heme state, and postmortem chemistry complicate the oxidation once it is started (142). Hence, the mechanisms outlined below should be viewed as guides rather than absolutes. More research should be focused on determining, by kinetic and product analyses, which reactions actually occur and are of practical importance in specific food systems. 

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