4- Hydroxynon-2-enal

HNE see 4-Hydroxynon-2-enal H NMR spectroscopy alkyl hydroperoxides, 104 trioxides, 179... 

Hydroxynon-2-enal (HNE) biomedical systems, 613-14, 670 colorimetric determination, 632, 669... 

Lithium compounds, bis(trimethylsilyl) peroxide reactions, 796-8, 799 Liver diseases, lipid hydroperoxides, 613 Liver microsomes, 4-hydroxynon-2-enal, 613-14... 

Protein cross-links may be also produced in reaction of 4-hydroxynonenal with lysine, histidine, serine, and cysteine residues, primarily via Michael addition (J5, R7, U8). These reactions occur spontaneously, but also may be catalyzed by certain glutatione 5-transferases. The glutathione transferase A4-4, which unlike other alpha-class glutathione transferases, shows high catalytic activity toward lipid peroxidation products such as 4-hydroxynon-2-enal, is the key enzyme for these reactions (B31). Products of protein coupling with aldehydes secondary to lipid peroxidation have a specific fluorescence, which can herald the protein oxidative modification process (CIO). 

Another important example of the Michael addition in biochemistry and molecnlar biology is the reaction of 4-hydroxynon-2-enal with amines and snlfydryl gronps (Winter, C.K., Segall, H.J., and Haddon, W.F., Formation of cyclic addncts of deoxygnanosine with the aldehyde trans-4-hydroxy-2-hexenal and fran.y-4-hydroxy-2-nonenal in vitro. Cancer Res. 46, 5682-5686, 1986 Sayre, L.M., Arora, P.K., Iyer, R.S., and Salomon, R.G., Pyrrole formation from 4-hydroxynonenal and primary amines, Chem. Res. Toxicol. 6, 19-22, 1993 Hartley, D.P, Ruth, J.A., and Petersen,... 

Fio. 9. GST substrates that represent components of oxidized lipid and DNA. Cholesterol-5,6-oxide (a) and 4-hydroxynon-2-enal (b) are detoxified by GST through thioether formation, whereas 9-hydroperoxy-linoleic acid (c) and 5-hydroperoxymethyl-uracil (d) are reduced by GST peroxidase activity. 

Compoimds that can isomerize to or equilibrate with 1,4-dicarbonyl systems are also potential pyrrole precursors. 4-Hydroxynon-2-enal, for example, condenses with primary amines to give 2-pentylpyrrole in a reaction which probably involves an isomerization of the imine intermediate (Scheme 70) <93MI 203-01 >. 

Annangudi SP, Deng Y, Gu X, Zhang W, Crabb JW, Salomon RG. Low-density lipoprotein has an enormous capacity to bind ( )-4-hydroxynon-2-enal (HNE) Detection and characterization of lysyl and histidyl adducts containing multiple molecules of HNE. Chem Res Toxicol 2008 21 1384-1395. 

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... 

Figure 3.75 Formation of 2 -deoxyguanine adducts with alk-2-enals and malondialdehyde R = H (acrolein), R = CH(0H)CH2CH3 (4-hydroxyhex-2-enal, R = ChKOHXCHjLCHj (4-hydroxynon-2-enal).

Hydroperoxides are removed from bonds in damaged phospholipid by activated phospholipase Aj and free hydroperoxide becomes a substrate for peroxidases. Otherwise, the oxidation of fatty acids results in the accumulation of lipid hydroperoxides and their secondary metabolites such as ( )-4-hydroxynon-2-enal and malondialdehyde, which react with proteins and DNA (see Section 3.8.1.12.1). 

Example 4-Hydroxynon-2-enal (4-HNE) is a major aldehydic product of lipid peroxidation (LPO), its products being indicators for oxidative stress. In order to introduce LPO products as biomarkers, a GC-MS method for 4-HNE detection in clinical studies [35] was developed using a sample volume of 50 pi of plasma. For improved GC separation and subsequent mass spectral detection the aldehyde is converted into the pentafluorobenzyl-hydroxylimine and the hydroxy group is tri-methylsilylated [36]. The TIC acquired in electron capture mode (EC, Chap. 7.4) exhibits 50 chromatographic peaks (Fig. 14.2). Those related to the target compounds can easily be identified from suitable RICs. The choice of potentially useful m/z values for RICs is made from the EC mass spectrum of the pure 4-HNE derivative (below). In this case, [M-HF], m/z 403, [M-HOSiMes] , m/z 333, and [CeFs]", m/z 167, are indicative, while [CH2C6F5] , m/z 181, is not. 

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