Cytochrome P450/NADPH-dependent formation of trans epoxides from trans -arachidonic acids

Roy, Uzzal; Loreau, Olivier; Balazy, Michael

doi:10.1016/j.bmcl.2003.11.054

Cited by 18 publications

(6 citation statements)

References 17 publications

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“…The effects of trans arachidonic acid isomers are not yet fully disclosed, although some evidence for their interaction with lipid enzymes has been gathered (45)(46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

Trans fatty acids and atopic eczema/dermatitis syndrome: The relationship with a free radical cis‐trans isomerization of membrane lipids

Ferreri

Angelini

Chatgilialoglu

et al. 2005

Lipids

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The formation of trans FA residues in membrane phospholipids may be due to a free radical-catalyzed isomerization process occurring to the cis unsaturated FA moieties. Radical stress is well documented in inflammatory processes of atopic diseases, but no data are yet available about a possible association with trans FA detected in these patients. We investigated the presence of trans lipid isomers in the erythrocyte and T-lymphocyte membranes of 26 children affected by atopic eczema/dermatitis syndrome (AEDS). Trans lipid isomers were found in both cell membranes, up to a total content of 2.7 and 4.9% of the FA composition, respectively. By using the geometrical trans lipid library derived from in vitro models of thiyl radical-catalyzed isomerization, oleic and arachidonic acid isomers were detected. The statistical significance was evaluated by comparison with an age-matched control group. These results suggest the role of an endogenous free radical isomerization path occurring to membrane unsaturated lipids, complementary to the dietary contribution, which can be involved in the lipid impairment in AEDS. This study contributes to lipidomic research regarding the double bond structure and the influence of a geometrical change of membrane lipids in physiology and diseases.

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“…The effects of trans arachidonic acid isomers are not yet fully disclosed, although some evidence for their interaction with lipid enzymes has been gathered (45)(46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

Trans fatty acids and atopic eczema/dermatitis syndrome: The relationship with a free radical cis‐trans isomerization of membrane lipids

Ferreri

Angelini

Chatgilialoglu

et al. 2005

Lipids

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“…Roy et al reported that certain trans double bonds of AA lead to formation of trans-EETs in CYP-catalyzed reactions [22]. The process of cis- to trans- AA isomerization can be mediated by nitrogen dioxide, a free radical byproduct of nitric oxide and nitrite oxidation or thiyl radicals [23,24].…”

Section: Discussionmentioning

confidence: 99%

Enzymatic and free radical formation of cis- and trans- epoxyeicosatrienoic acids in vitro and in vivo

Aliwarga

Raccor

Lemaître

et al. 2017

Free Radical Biology and Medicine

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Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid (AA) oxidation that have important cardioprotective and signaling -6 polyunsaturated fatty acid (PUFA) that is prone to autoxidation. Although hydroperoxides and isoprostanes are major autoxidation products of AA, EETs are also formed from the largely overlooked peroxyl radical addition mechanism. While autoxidation yields both cis- and trans-EETs, cytochrome P450 (CYP) epoxygenases have been shown to exclusively catalyze the formation of all regioisomer cis-EETs, on each of the double bonds. In plasma and red blood cell (RBC) membranes, cis- and trans-EETs have been observed, and both have multiple physiological functions. We developed a sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay that separates cis- and trans- isomers of EETs and applied it to determine the relative distribution of cis- vs. trans-EETs in reaction mixtures of AA subjected to free radical oxidation in benzene and liposomes in vitro. We also determined the in vivo distribution of EETs in several tissues, including human and mouse heart, and RBC membranes. We then measured EET levels in heart and RBC of young mice compared to old. Formation of EETs in free radical reactions of AA in benzene and in liposomes exhibited time- and AA concentration-dependent increase and trans-EET levels were higher than cis-EETs under both conditions. In contrast, cis-EET levels were overall higher in biological samples. In general, trans-EETs increased with mouse age more than cis-EETs. We propose a mechanism for the non-enzymatic formation of cis- and trans-EETs involving addition of the peroxyl radical to one of AA's double bonds followed by bond rotation and intramolecular homolytic substitution (SHi). Enzymatic formation of cis-EETs by cytochrome P450 most likely occurs via a one-step concerted mechanism that does not allow bond rotation. The ability to accurately measure circulating EETs resulting from autoxidation or enzymatic reactions in plasma and RBC membranes will allow for future studies investigating how these important signaling lipids correlate with heart disease outcomes.

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“…As reference, the chemical shifts of an ester-linked and an amide-linked product of oleic acid and ethanolamine are shown as reported by Ottria et al [39]. Characteristic shifts for the ethanolamide entities, which could be found in our analytes, are printed in bold in vivo [43,44]. The absence of all FAEAs studied in this paper other than VEA and OEA could possibly be explained by the consideration that cis/trans-isomerization takes place at sites in the organism where no FAEAs are formed and hence cannot be detected in plasma.…”

Section: Detection Of Faeas By Uhplc-esi-ms/msmentioning

confidence: 94%

Identification of the oleic acid ethanolamide (OEA) isomer cis-vaccenic acid ethanolamide (VEA) as a highly abundant 18:1 fatty acid ethanolamide in blood plasma from rats and humans

et al. 2016

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The endocannabinoid system is important in various physiological pathways, especially the regulation of food intake. It consists of endocannabinoids like 2-arachidonoyl-glycerol (2-AG) or the fatty acid ethanolamide archachidonoyl-ethanolamide (AEA) with binding affinity to cannabinoid receptors. Further, fatty acid ethanolamides (FAEAs) influence the endocannabinoid system without affecting cannabinoid receptors by using independent physiological pathways. Among FAEAs, oleic acid ethanolamide (OEA) gained importance because of its promising ability to reduce food intake. By ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS), we detected a chromatographically separated molecule in plasma samples from rats and humans with identical mass and fragmentation patterns as those of OEA. Via synthesis and extensive analysis of ethanolamides of different cis/trans- and position isomers of oleic acid (cis9-18:1), we could identify the unknown molecule as vaccenic acid (cis11-18:1) ethanolamide (VEA). In this study we identified VEA as the most abundant 18:1 FAEA in rat plasma and the second most abundant 18:1 FAEA in human plasma.

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Cytochrome P450/NADPH-dependent formation of trans epoxides from trans -arachidonic acids

Cited by 18 publications

References 17 publications

Trans fatty acids and atopic eczema/dermatitis syndrome: The relationship with a free radical cis‐trans isomerization of membrane lipids

Trans fatty acids and atopic eczema/dermatitis syndrome: The relationship with a free radical cis‐trans isomerization of membrane lipids

Enzymatic and free radical formation of cis- and trans- epoxyeicosatrienoic acids in vitro and in vivo

Identification of the oleic acid ethanolamide (OEA) isomer cis-vaccenic acid ethanolamide (VEA) as a highly abundant 18:1 fatty acid ethanolamide in blood plasma from rats and humans

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