Lipids oxidised, reactions

These LO or LOO radicals initiate the lipid-peroxidation reaction in which the polyunsaturated fatty acids (mainly 18 2 and 20 4) of the LDL particle are rapidly oxidised to lipid hydroperoxides. 

Similarly to a-tocopherol, other tocopherols and tocotrienols also react with oxidised lipids Some reaction products of y-tocopherol, such as tocopherol red (tocored, 5-40, arising during... 

Ferryl myoglobin species (either the FeIV=0 itself or the protein free radicals) are capable of catalysing lipid peroxidation in model membranes [238], erythrocytes [239] and low-density lipoproteins [240]. They can also oxidise phenols, styrene, 3-carotene and ascorbate [211], At high peroxide levels, protein cross-linking is observed, followed by iron release which can result in Fenton chemistry in vitro. However, it is difficult to see how the peroxide haem ratio can ever be high enough in vivo to initiate these reactions. 

Lipid hydroperoxides arise in membranes and in oxidised LDL as a direct consequence of the intervention by a-T in terminating chain reactions, as well as from the chain reactions themselves. The possibility exists that catalysis by divalent transition metal cation complexes may cause the re-formation of lipid-peroxyl radicals or of other radical species such as the alkoxyl radical. The rate of reaction of Fe3+ with lipid hydroperoxides is much slower than the rate of... 

Reactions 11,13) as well as recycling the haem proteins for further oxidative events. The lipid peroxyl radicals formed during the modification of the polyunsaturated fatty acid sidechains of lipids, can amplify lipid peroxidation, oxidise cholesterol and can react with proteins, impairing the functions of critical enzyme and receptor systems ... 

The second metabolic pathway which we have chosen to describe is the tricarboxylic acid cycle, often referred to as the Krebs cycle. This represents the biochemical hub of intermediary metabolism, not only in the oxidative catabolism of carbohydrates, lipids, and amino acids in aerobic eukaryotes and prokaryotes, but also as a source of numerous biosynthetic precursors. Pyruvate, formed in the cytosol by glycolysis, is transported into the matrix of the mitochondria where it is converted to acetyl CoA by the multi-enzyme complex, pyruvate dehydrogenase. Acetyl CoA is also produced by the mitochondrial S-oxidation of fatty acids and by the oxidative metabolism of a number of amino acids. The first reaction of the cycle (Figure 5.12) involves the condensation of acetyl Co and oxaloacetate to form citrate (1), a Claisen ester condensation. Citrate is then converted to the more easily oxidised secondary alcohol, isocitrate (2), by the iron-sulfur centre of the enzyme aconitase (described in Chapter 13). This reaction involves successive dehydration of citrate, producing enzyme-bound cis-aconitate, followed by rehydration, to give isocitrate. In this reaction, the enzyme distinguishes between the two external carboxyl groups... 

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... 

In system (6) peroxidation of membrane lipids can be initiated not only by ubiquinone, but also by nicotinamides. This can be explained if one bears in mind that, as can be seen from reaction (3), redox equilibrium between the oxidized and reduced forms of coenzymes is accomplished through intermediate stages at which radicals are formed. For instance, NADH is not oxidised immediately to NAD+ but passes through the stages of formation of NAD or NADH+. Since nicotinamide does not penetrate into the membrane phase, it itself cannot cause oxidation of hydrocarbon residues of fatty acids, it could be supposed that NADH initiated peroxidation through peroxide anions O2, which can be formed according to the following reaction ... 

Nitric oxide can both promote and inhibit lipid peroxidation (Hogg and Kalyanaraman (1999). By itself, NO acts as a potent inhibitor of the lipid peroxidation chain reaction by scavenging propagatory lipid peroxyl radicals (formula [81]). It can also inhibit many potential initiators of lipid peroxidation, such as peroxidase enzymes. In the presence of 02 , NO forms peroxynitrite (see equation [46]), a powerful oxidant capable of initiating lipid peroxidation and oxidising lipid soluble antioxidants. 

Reaction products of reactive aldehydes derived from oxidised lipids, such as acrolein, ( )-4-hydroxynon-2-enal and malondi-aldehyde, with lysine, arginine and other amino acids are described as examples in Section 4.7.5.6. These products, ALE (advanced lipoxidation end products), formed in vivo are markers of oxidative stress in the organism. Reaction mechanisms are discussed in Section 3.8.1.12.1. As the final reaction products, proteins and oxidised lipids also form dark insoluble macromolecular products that contain variable proportions of lipid and protein fractions. In particular, such products include protein oligomers, proteins with oxidised sulfur amino acids, proteins containing imine bonds (C=N) formed by reaction with aldehydes or hydroperoxides (they mostly arise from the -amino group of bound lysine) and... 

Phenolic compounds known as polyphenols (such as phenohc acids and flavonoids) are easily oxidised by atmospheric oxygen in reactions catalysed by oxidoreductases (o-diphenokO, oxidoreduc-tases). These reactions are known as enzymatic browning reactions (see Section 9.12). Autoxidation of plant phenols catalysed by heavy metal ions (mainly cupric and ferric ions) and oxidation by lipid hydroperoxides lead to similar products. The products of oxidation of the so-called o-diphenok (1,2-dihydroxybenzenes) are o-quinones (1,2-benzoquinones), highly reactive compounds that react with proteins (amino acids) and other food components with the formation of dark-coloured polymeric products resistant to proteolysis. 

Oxidation of food constituents and other reaction of oxidised lipids... 

Other significant reactions are reactions of oxidised lipids with phenolic compounds, many of which are used as antioxidants (see Section 11.2.2). 

The main agents damaging proteins are hydroxyl radicals (HO ), singlet oxygen ( 02) and superoxide radicals (HOj ). Reactions are analogous to those in foods and can result in loss of enzymatic activity, cell cytolysis and cell death. Damaged proteins in biomembranes are often associated with oxidised lipids. 

Tocopherols and tocotrienols are monoethers of the respective hydroquinones and are therefore readily oxidised, for example by ferric ions, Hpid hydroperoxides and other oxidants. This creates the corresponding quinones (tocopheryl quinones or tocoquinones). Tocopheryl quinones can be reduced to tocopheryl hydroquinones (tocohydroquinones). The most important reactions are those with oxidised lipids (Figures 5.7 and 5.8). 

The antioxidant activity of vitamin E in emulsions depends on the structure of the emulsions and the presence of other antioxidants, such as 3,5-di-tert-butyl-4-hydroxytoluene (BHT) and ascorbyl pahnitate. Temperature plays an important part, as does, particularly, the presence of oxygen and the stability of the radicals of tocopherols produced as intermediates in reactions with oxidised lipids. At 80 °C in the presence of air, 5-tocopherol, for example, is the only vitamin form which partially withstands heating for 6 h, when used as an antioxidant to protect linoleic acid against autoxidation. In an atmosphere containing only 10% oxygen (hah of the amount of oxygen in air), P- and y-tocopherols are also present, but a-tocopherol and aU tocotrienols are absent. At 60 °C in the absence of oxygen, all tocopherols and tocotrienols are present. 

O-alkyl- a-tocopherol Figure 5.7 Main reaction products of a-tocopherol with oxidised lipids. 

Figure 5.8 shows, as an example, the most important products of a-tocopherol in reactions with oxidised lipids. The main products. 

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