Oxidation-susceptible phospholipids

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. 

The fluorophore should be stable under the conditions of measurement. Some fluorophores (e.g., parinaric acid), for example, may be incorporated into phospholipids in natural membranes.(67) Conversely, phospholipids with the fluorophore attached to one of the fatty acyl chains (e.g., DPH-PC) may be cleaved by the action of phospholipases. Also, DPH is susceptible to photobleaching so that a low excitation intensity has to be used. Parinaric acids are liable to oxidize and therefore have to be kept under argon. 

When the microencapsulated liposomes are left untreated the lipid bilayer provides a barrier to diffusion through which the entrapped protein does not pass until the liposomes gradually become leaky, primarily due to oxidation of the phospholipid side chains. This mechanism results in a delayed release. Triton or sonic treatment of the microencapsulated liposomes provide pulsed re ease. Since both detergent and sonication disrupt lipid bi ayers, the mechanism by which pulsed release is achieved may be that these stimuli initially disrupt the liposomes and then the lipid reforms around some of the protein solution inside the capsule, possibly in an altered lamellar form alternatively, the treatment could disrupt only the more susceptible liposomes, leading to two phases of release, first from the freed protein and later from protein that remained liposome-entrapped. 

Because of animal biohydrogenation, the content of polyunsaturated acids in milk is low, currently reported at about 5% (Smith et al 1978), and is associated mostly with the phospholipids. While quantitatively unimportant, these acids are the most susceptible targets of oxidation and provide the essential fatty acids (EFA), mostly cis, cis-9, 12-18 2. 

Lipids are susceptible to oxidation and, therefore, analytical protocols are required to measure their quality. Not all lipids have the same degree of susceptibility to oxidation. Many factors are responsible for a lipid s tendency to oxidize, including the presence of catalysts, oxidative enzymes, radiation, and a lipid-air interface, as well as the oxygen partial pressure, the incorporation of oxygen into the product, and the presence of metal ions. The most important factor is the degree of unsaturation of the lipid itself. The majority of a food product s polyunsaturated fatty acids (PUFAs) are generally contained in phospholipids, which are consequently more prone to autoxi-dation than the triacylglycerol fraction. 

Hydrolysis and oxidation are the two primary degradation routes to which liposomal phospholipids are susceptible. Hydrolytic attack at the fatty acyl carbonyl will produce free fatty acids and lysophosphatides [e.g., lyso-phosphatidyl choline (LPC)]. Hydrolysis generally follows Lrst-order... 

Xanthine oxidoreductase, a metalloprotein abundant in the MFGM, may also be partially responsible for the susceptibility of the membrane to lipid oxidation (Allen and Humphries, 1977 Aurand et al., 1977 Bruder et al., 1982 Bouzas et al., 1985). Allen and Humphries (1977) prepared two protein fractions from MFGM and found that oxidative activity resided almost entirely in the first fraction, devoid of phospholipids, but richer in Xanthine oxidoreductase. They proposed that the metalloprotein, and not... 

Prostaglandins are synthesized as shown in Fig. 13-17 from arachidonic acid in a metabolic pathway that begins with plasma membrane phospholipids. The double-bond arrangement in the carbon chain of arachidonic acid, C2o 4A5,8,ll,14, makes the fatty acid very susceptible to oxidation... 

Such imbalanced antioxidant systems in schizophrenia could lead to oxidative stress- and ROS-mediated injury as supported by increased lipid peroxidation products and reduced membrane polyunsaturated fatty acids (PUFAs). Decrease in membrane phospholipids in blood cells of psychotic patients (Keshavan et al., 1993 Reddy et al., 2004) and fibroblasts from drug-naive patients (Mahadik et al., 1994) as well as in postmortem brains (Horrobin et al., 1991) have indeed been reported. It has also been suggested that peripheral membrane anomalies correlate with abnormal central phospholipid metabolism in first-episode and chronic schizophrenia patients (Pettegrewet al., 1991 Yao et al., 2002). Recently, a microarray and proteomic study on postmortem brain showed anomalies of mitochondrial function and oxidative stress pathways in schizophrenia (Prabakaran et al., 2004). Mitochondrial dysfunction in schizophrenia has also been observed by Ben-Shachar (2002) and Altar et al. (2005). As main ROS producers, mitochondria are particularly susceptible to oxidative damage. Thus, a deficit in glutathione (GSH) or immobilization stress induce greater increase in lipid peroxidation and protein oxidation in mitochondrial rather than in cytosolic fractions of cerebral cortex (Liu et al., 1996). 

Lipid peroxidation of biological membranes is a destructive process, proceeding via an autocatalytic chain reaction mechanism [73]. Membrane phospholipids contain hydrogen atoms adjacent to unconjugated olefinic bonds, which make them highly susceptible to free radical oxidation. This is characterised by an initiation step, one or more propagation steps and a termination step [1], which may involve the combination of two radical species or interaction with an antioxidant molecule such as vitamin E. The products formed from such reactions include lipid peroxides, lipid alcohols and aldehydic by-products such as malondialdehyde and 4 hydroxynonenal [73]. 

Since TTA is poorly oxidizable it is likely to be esterified into other lipids, primarily phospholipids. Thus, TTA readily enters the cell membrane in which it influences membrane properties. Moreover, TTA treatment influences the PUFA composition of membranes. As TTA changes the membrane PUFA content and possesses antioxidant properties, it may influence the susceptibility to lipid peroxidation. In addition to functioning as an antioxidant itself, TTA changes the antioxidant defense system in hepatocytes. This indicates that TTA affects the cellular oxidative situation. 

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