Aldehydic breakdown products of lipid peroxidation

Following peroxidation of n-6 (linoleic, y-linolenic and arachidonic acids) and n-3 (a-linolenic and docosahexaenoic acids) fatty acids, relatively unstable fatty acid hydroperoxides may be converted by consecutive scission, fission, rearrangement and oxidation reactions into more stable carbonyls. These include  

It has been suggested that measurement of the aldehydic breakdown products of lipid peroxidation is the most reliable indicator that the process has occurred in vivo in normal or pathological conditions (Esterbauer et al., 1988), but there is very little information as to the rate of production of these compounds in vivo (Yoshino et al., 1986 Tomita et al., 1987), or of their relative proportions. 

This section is concerned with thin-layer and high-performance liquid chromatographic/mass spectrophotometric techniques used in the analyses of these compounds, which are often found to be present 

ft unsaturated carbonyls exhibit an ultraviolet absorbance with an intense maximum in the range 220 nm and a weak one at 280 nm, depending on the polarity of their solvent (hexane 215 nm, methanol 221 nm, water 224 nm) (Fig. 5.5). This characteristic has been extensively exploited for the characterization of 4-hydroxynonenal produced during the peroxidation of hepatic tissues. Table 5.1 lists the molar absorption co-efficients for free hydroxyalkenals (average e= 10000-14000 M- cm-1 (Esterbauer and Weger, 1967). 

Trace amounts of aldehydes, particularly acetaldehyde, propanal 

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Cleavage of the carbon bonds during lipid peroxidation reactions results in the formation of aldehydic products such as cytotoxic alkanals and alkenals, as well as alkanes. The breakdown products of lipid peroxidation, alkanals such... 

If the process of lipid peroxidation continues unimpeded, the consequences include the release of toxic breakdown products and the eventual destruction of the lipid component of biological membranes (S28). Such breakdown products include the aldehydes, malondialdehyde, 2-alkenals, and 4-hydroxyalkenals. A number of mammalian GST isoenzymes are highly efficient in the detoxification of these compounds (Dl). Indeed, 4-hydroxynonenal is one of the best GST substrates identified to date, and with one of the rat GST isoenzymes the K JK value obtained indicates that catalysis proceeds relatively close to the diffusion-controlled limit. Cholesterol-5,6-epoxide is a further example of a byproduct of lipid peroxidation, and the conjugation of GSH to this weakly mutagenic compound is catalyzed by certain GST (M18). 

These measurements include the F2 isoprostanes—the oxidation products of arachi-donic acid—and methods require mass spectrometry or immunoassay. Other measures of lipid peroxidation include hydroperoxides by luminometry or colorimetric assays, or a third colorimetric measurement of aldehyde products (TEAR) with thiobarbituric acid where malondialdehyde is measured malondialdehyde is an end-product derived from the breakdown of polyunsaturated fatty acids and esters. 

Lipid peroxidation (Figure 14.5) is the initiating reaction in a cascade of events, starting with the oxidation of unsaturated fatty acids to form lipid hydroperoxides, which then break down to yield a variety of end products, mainly aldehydes, which can go on to produce toxicity in distal tissues. For this reason cellular damage results not only from the breakdown of membranes such as those of the endoplasmic reticulum, mitochondria, and lysosomes but also from the production of reactive aldehydes that can travel to other tissues. It is now thought that many types of tissue injury, including inflammation, may involve lipid peroxidation. 

During the last steps of lipid oxidation, the fatty acid chains breakdown to give aldehydes (hexanal, propanal, malondialdehyde), depending on the lipid structure. These compounds react with thiobarbituric acid to give coloured compounds the measurement of which at 535 nm can be used to follow the oxidation process in its terminal phase [91]. In addition, hexanal, which is an important decomposition product of n-6 polyunsaturated fatty acid peroxidation in rat liver samples, human red blood cell membranes, and human LDL (low density lipoproteins), can be measured by headspace gas chromatography [92]. Malondialdehyde, another important decomposition product, can also be analysed by GC (Gas Chromatography) [93], and, after reaction with urea to give 2-hydroxypyrimidine, by HPLC [94]. 

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