Polyunsaturated fatty acids mediated oxidations

Polyunsaturated fatty acids are oxidized by enzymatic and nonenzymatic pathways. Nonenzymatic oxidation is a free-radical mediated peroxidation. It is a chain reaction providing a continuous supply of free radicals that initiate further peroxidation. The whole process can be depicted as follows [21] ... 

Lipoxygenases catalyze oxidation of polyunsaturated fatty acids in plant lipids. Within animal tissues the lipoxygenase-catalyzed reaction of arachidonic acid with 02 is the first step in formation of Ieukotrienes and other mediators of inflammation. These reactions are discussed in Chapter 21. 

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 is a free radical-mediated, chain reaction resulting in the oxidative deterioration of polyunsaturated fatty acids (PUFAs) defined for this purpose as fatty acids that contain more than two double covalent carbon-carbon bonds. Singlet oxygen can produce lipid hydroperoxides in unsaturated lipids by non-radical processes (Pryor and Castle, 1984), but the reaction usually requires a radical mechanism (Porter, 1984). Polyunsaturated fatty acids are particularly susceptible to attack by free radicals. Lipid peroxidation is a complex process, and three distinct phases are recognized (a) initiation, (b) propagation and (c) termination (see Fig. 2.10). 

Lipid oxidation is an important topic in food science and technology since the reaction of polyunsaturated fatty acids with oxygen leads to rancidity and quality loss. The same process is important in human health, since the polyunsaturated fatty acids from lipids present in blood plasma (low density lipoproteins, LDL) are oxidised by oxygen in a free radical mediated reaction, promoting the development of atherosclerosis. LDL enters the arterial wall from the plasma and is oxidised locally within the wall by oxidising agents derived from the cells present in atherosclerotic... 

Oxidation of polyunsaturated fatty acids (PUFA) in lipoproteins may be mediated by reactive species such as radicals, transition metals, other electrophiles, and by enzymes. Once initiated, oxidation of lipids may proceed by a chain reaction, illustrated in Fig. 4 (R5). In step I, an oxidant captures an electron from a PUFA to produce a lipid radical. In step 2, after rearrangement, the conjugated diene radical reacts rapidly with singlet oxygen to produce a lipid peroxide radical, which is the kinetically preferred reaction (step 3) (B5). The chain can be terminated if the lipid radical reacts with an antioxidant to produce a stable peroxide (step 4). Otherwise, the peroxyl radical can react with another polyunsaturated fatty acid as shown in step 5 to perpetuate a chain reaction. The chain reaction requires production of lipid peroxides, giving it the name peroxidation. Fatty acids oxidized in the core are largely triglycerides and cholesterol esters, while toward the outer layer fatty acids in phospholipids are oxidized. 

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