Polyunsaturated fatty acids PUFAs peroxidation

Lipid peroxidation is a radical-mediated chain reaction resulting in the degradation of polyunsaturated fatty acids (PUFAs) that contain more than two covalent carbon-carbon double bonds (reviewed by Esterbauer et al., 1992). One of the major carriers of plasma lipids is LDL, a spherical molecule with a molecular weight of 2.5x10 . A single LDL particle contains 1300 PUFA molecules (2700 total fatty-acid molecules) and is... 

It is now widely appreciated that polyunsaturated fatty acids (PUFAs) are highly susceptible to oxidative damage. Indeed, the process of lipid peroxidation was broadly defined as the oxidative deterioration of polyunsaturated lipids by Tappel (1979). The presence of a double... 

FIGURE 32-6 Lipid peroxidation leads to fragmentation or oxidation of polyunsaturated fatty acids (PUFA). HO, hydroxyl radical LO, lipid alkoxylradical LOO, lipid peroxyl radical 0 2, superoxide radical O, atomic oxygen radical. (From Hall in [3].)... 

PTFE polytetrafluoroethylene PUFA polyunsaturated fatty acid PV peroxide value PVDF polyvinylidene difluoride PVP polyvinylpyrrolidone PVPP polyvinylpolypyrolidone RAS retronasal aroma stimulator RDA recommended dietary allowance RF radio frequency RFI relative fluorescence intensity RI retention index RNU relative nitrogen utilization ROESY rotational nuclear Overhauser enhancement spectroscopy RP-HPLC reversed-phase HPLC RPER relative protein efficiency ratio RS resistant starch RT retention time RVP relative vapor pressure S sieman (unit of conductance)... 

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). 

Primary targets for attack by oxygen-derived free radical species are the polyunsaturated fatty-acid (PUFA) moieties of membrane phospholipids. Attack on low-density lipoprotein PUFA (LDL PUFA) must also be considered and is of primary importance in the consideration of the aetiology of atherosclerosis. The mechanism of all such peroxidation processes is likely to be the same and the inhibitory effect of antioxidants toward PUFA can be considered to be... 

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). 

Due to a high concentration of substrate polyunsaturated fatty acids (PUFAs) in cells, lipid peroxidation is a major outcome of free radical-mediated injury (Montine et al, 2002a, b). A critically important aspect of hpid peroxidation... 

Radical processes involving membrane phospholipids are mainly referring to the peroxidation of polyunsaturated fatty acids (PUFA). In the previous decade, reactions of PUFA with a variety of RS radicals were studied. Pentadienyl-type radicals (Chart 5, left structure) and radical... 

The formation and reactions of guanine radicals in DNA and their reactions in the presence of carbon-centered radicals derived from lipid molecules provide instructive examples of free radical reactions in solutions involving these biologically relevant species. The reactivities of free radicals derived from biomolecules depend on their structures. The carbon-centered radicals produced by either by hydrogen atom abstraction or the addition of oxyl radicals to double bonds of polyunsaturated fatty acids (PUFAs) are primary intermediates of lipid peroxidation... 

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. 

It is largely accepted that a high dietary intake of poly-unsaturated fatty adds (PUFA) in the a>-3 series has beneficial effects. Recently, cellular lipid metabolism has been suggested as a target for cancer therapy. Cancer cells, compared with normal cells, seem to be vulnerable to exposure of certain polyunsaturated fatty acids (PUFAs), especially those in the o -3 series. Characteristic for these compounds are their poor abihty to be oxidized in the cell due to multiple double bonds. They are however likely to be ester-rfied to oflier Upids, and their incorporation into membrane phosphohpids will influence membrane properties such as fluidity, protein interactions and susceptibility to lipid peroxidation. The hypohpidemic properties of some (0-3 fatty acids, such as EPA, are probably e lained by an induction of mitochondrial P -oxidation that is not found after adrninistration of the non-hypolipidemic (o-3 PUFA docosahexaenoic acid (DHA)." However, both eicosapentaenoic acid (EPA) and DHA cause increased peroxisomal... 

A third study focused on the effect of CLA and vitamin A on the polyunsaturated fatty acid (PUFA) composition, chemiluminescence and peroxidizability index of microsomes and mitochondria isolated from rat liver (43). The PUFA composition of microsomes and mitochondria changed by CLA and vitamin A treatment. The simultaneous analysis of peroxidizability index, chemiluminescence and fatty acid composition demonstrated that CLA is more effective than vitamin A in protecting microsomes or mitochondria against peroxidative damage. 

Polyunsaturated fats from vegetable oils—A diet rich in polyunsaturated fatty acids (PUFA) but poor in vitamin E might raise the requirement for selenium because (1) PUFA may be readily converted to toxic peroxides by various metabolic processes unless there is sufficient vitamin E to prevent this conversion, and (2) selenium is needed to activate the enzyme (gluthathione peroxidase) which destroys the peroxides. 

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