Routes to 4-Hydroxynonenal: Fundamental Issues in the Mechanisms of Lipid Peroxidation

Schneider, Claus; Porter, Ned A.; Brash, Alan R.

doi:10.1074/jbc.r800001200

Cited by 235 publications

(215 citation statements)

References 45 publications

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“…There are three main mechanisms by which a carbon-carbon bond can be cleaved, as described and reviewed in several key publications by researchers at Vanderbilt University and elsewhere [16,[24][25][26][27]. The principles have mostly commonly been explored with linoleic acid and have focused on the formation of 4-hydroxy-2-nonenal (HNE), owing to the fact that it is one of the most abundantly formed lipid peroxidation products and has interesting biological effects [8,28,29].…”

Section: Aldehydes Are Fragmentation Products Of Oxidized Lipidsmentioning

confidence: 99%

“…Following its discovery in the 1960s [35], it is now classed as one of the major aldehydes formed during lipid peroxidation of ω-6 polyunsaturated fatty acids and it can be considered a useful biomarker of lipid peroxidation [18]. The non-enzymatic processes of HNE generation mainly occur by oxygen radicaldependent reactions and have been extensively studied by several groups as mentioned above; several detailed reviews are also available [15, 16,24]. The strong interest in 4-hydroxynonenal relates to its high reactivity due to its potential for Michael addictions and Schiff-base formation [44].…”

Section: Alkanalsmentioning

confidence: 99%

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Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds

Sousa

Pitt

Spickett

2017

Free Radical Biology and Medicine

138

105

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The process of lipid oxidation generates a diverse array of small aldehydes and carbonyl-containing compounds, which may occur in free form or esterified within phospholipids and cholesterol esters. These aldehydes mostly result from fragmentation of fatty acyl chains following radical oxidation, and the products can be subdivided into alkanals, alkenals (usually D,β-unsaturated), γ-substituted alkenals and bis-aldehydes.Isolevuglandins are non-fragmented di-carbonyl compounds derived from H 2 -isoprostanes, and oxidation of the ω-3-fatty acid docosahexenoic acid yield analogous 22 carbon neuroketals. Non-radical oxidation by hypochlorous acid can generate D-chlorofatty aldehydes from plasmenyl phospholipids. Most of these compounds are reactive and have generally been considered as toxic products of a deleterious process. The reactivity is especially high for the D,β-unsaturated alkenals, such as acrolein and crotonaldehyde, and for γ-substituted alkenals, of which 4-hydroxy-2-nonenal and 4-oxo-2-nonenal are best Page | 2 known. Nevertheless, in recent years several previously neglected aldehydes have been investigated and also found to have significant reactivity and biological effects; notable examples are 4-hydroxy-2-hexenal and 4-hydroxy-dodecadienal. This has led to substantial interest in the biological effects of all of these lipid oxidation products and their roles in disease, including proposals that HNE is a second messenger or signalling molecule.However, it is becoming clear that many of the effects elicited by these compounds relate to their propensity for forming adducts with nucleophilic groups on proteins, DNA and specific phospholipids. This emphasizes the need for good analytical methods, not just for free lipid oxidation products but also for the resulting adducts with biomolecules. The most informative methods are those utilizing HPLC separations and mass spectrometry, although analysis of the wide variety of possible adducts is very challenging. Nevertheless, evidence for the occurrence of lipid-derived aldehyde adducts in biological and clinical samples is building, and offers an exciting area of future research. AbbreviationsAcr-dG, 1,N2-propanodeoxyguanosine; AGEs, advanced glycation end-product; ALEs, advanced lipoxidation end product; ApoB100, apolipoprotein B100; ApoE, apolipoprotein E; ARP, aldehyde reactive probe; AspN, endoproteinase AspN (flavastacin); βLG, β-lactoglobulin; BHZ, biotin hydrazide; BN-PAGE, blue native polyacrylamide gel

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Section: Aldehydes Are Fragmentation Products Of Oxidized Lipidsmentioning

confidence: 99%

Section: Alkanalsmentioning

confidence: 99%

Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds

Sousa

Pitt

Spickett

2017

Free Radical Biology and Medicine

138

105

View full text Add to dashboard Cite

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“…The free radical nature of lipid autoxidation was established by Bolland, Bateman and colleagues at the British Rubber Producers' Research Association (Schneider et al 2008). They defined the three well-recognized stages of the process as initiation, propagation, and termination.…”

Section: Autoxidationmentioning

confidence: 99%

“…Two main paradigms for initiation in lipid autoxidation have been advanced (Schneider et al 2008). The reactions of transition metals (eqs 2 to 4) or of chemical initiators present in the lipid sample are thought to generate a pool of radicals which initiate new autoxidation chains.…”

Section: Autoxidationmentioning

confidence: 99%

“…Such dimer fatty acids would be prone to breakage of the cross-molecular peroxide bond and would produce, as depicted in Fig. 1, free radicals and aldehydes (Schneider et al 2008). This illustrates the expected importance of the dimer fatty acids not only in the autocatalytic radical supply but also in the formation of volatile secondary autoxidation products.…”

Section: Autoxidationmentioning

confidence: 99%

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Autoxidation of Conjugated Linoleic Acid Methyl Ester in the Presence of α‐Tocopherol: The Hydroperoxide Pathway

Pajunen

Johansson

Hase

et al. 2008

Lipids

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The autoxidation of conjugated linoleic acid (CLA) is poorly understood in spite of increasing interest in the beneficial biological properties of CLA and growing consumption of CLA-rich foods. In this thesis, the autoxidation reactions of the two major CLA isomers, 9-cis,11-transoctadecadienoic acid and 10-trans,12-cis-octadecadienoic acid, are investigated. The results contribute to an understanding of the early stages of the autoxidation of CLA methyl ester, and provide for the first time a means of producing and separating intact CLA methyl ester hydroperoxides as well as basic knowledge on lipid hydroperoxides and their hydroxy derivatives.Conjugated diene allylic monohydroperoxides were discovered as primary autoxidation products formed during autoxidation of CLA methyl esters in the presence and absence oftocopherol. This established that one of the autoxidation pathways of CLA methyl ester is the hydroperoxide pathway.Hydroperoxides were produced from the two major CLA methyl esters by taking advantage of the effect of -tocopherol to promote hydroperoxide formation. The hydroperoxides were analysed and separated first as methyl hydroxyoctadecadienoates and then as intact hydroperoxides by HPLC. The isolated products were characterized by UV, GC-MS, and NMR techniques. In the presence of a high amount of -tocopherol, the autoxidation of CLA methyl ester yields six kinetically-controlled conjugated diene monohydroperoxides and is diastereoselective in favour of one particular geometric isomer as a pair of enantiomers. The primary autoxidation products produced from the two major CLA isomers include new positional isomers of conjugated diene monohydroperoxides, the 8-, 10-, 12-, and 14-hydroperoxyoctadecadienoates. Furthermore, two of these new positional isomers have an unusual structure for a cis,trans lipid hydroperoxide where the allylic methine carbon is adjacent to the cis instead of the usual trans double bond.The 1 H and 13 C NMR spectra of nine isomeric methyl hydroxyoctadecadienoates and of ten isomeric methyl hydroperoxyoctadecadienoates including the unusual cis,trans hydroperoxides, i.e. Me 8-OOH-9c,11t and Me 14-OOH-10t,12c, were fully assigned with the aid of 2D NMR spectroscopy. The assigned NMR data enabled determination of the effects of the hydroxyl and hydroperoxyl groups on the carbon chemical shifts of CLA isomers, identification of diagnostic signals, and determination of chemical shift differences of the olefinic resonances that may help with the assignment of structure to as yet unknown lipid hydroperoxides either as hydroxy derivatives or as intact hydroperoxides.A mechanism for the hydroperoxide pathway of CLA autoxidation in the presence of a high amount of -tocopherol was proposed based on the characterized primary products, their relative distribution, and theoretical calculations. This is an important step forward in CLA research, where exact mechanisms for the autoxidation of CLA have not been presented before. Knowledge of these hydroperoxide formation steps is of cr...

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Lipid Peroxidation and Nitration

Davies¹,

Guo²

2013

Molecular Basis of Oxidative Stress

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Routes to 4-Hydroxynonenal: Fundamental Issues in the Mechanisms of Lipid Peroxidation

Cited by 235 publications

References 45 publications

Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds

Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds

Autoxidation of Conjugated Linoleic Acid Methyl Ester in the Presence of α‐Tocopherol: The Hydroperoxide Pathway

Lipid Peroxidation and Nitration

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