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| Names | |
|---|---|
| IUPAC name 8-[3-[(Z)-Oct-2-enyl]oxiran-2-yl]octanoic acid | |
| Other names 9,10-Epoxy-12Z-octadecenoic acid; 9(10)-EpOME, 9R,10S-EpOME and 9S,10R-EpOME | |
| Identifiers | |
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3D model (JSmol) |
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| ChEBI |
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| ChEMBL |
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| ChemSpider |
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| UNII |
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| Properties | |
| C18H32O3 | |
| Molar mass | 296.451 g·mol−1 |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Coronaric acid (leukotoxin orleukotoxin A) is a mono-unsaturated,epoxide derivative of the di-unsaturated fatty acid,linoleic acid (i.e. 9(Z),12(Z) octadecadienoic acid). It is a mixture of the two optically activeisomers of 12(Z) 9,10-epoxy-octadecenoic acid. This mixture is also termed 9,10-epoxy-12Z-octadecenoic acid or 9(10)-EpOME[1] (forEpoxy-Octadeca-MonoEnoic acid) and when formed by or studied in mammalians, leukotoxin.
Coronaric acid is found in the seed oils derived from plants in thesunflower family, such asHelianthus annuus[2] andXeranthemum annuum.[3]
Coronaric acid is also formed by the cells and tissues of various mammalian (including human) species through the metabolism of linoleic acid bycytochrome P450 (CYP)epoxygenase enzymes. These CYPs (CYP2C9 and probably other CYPs that metabolizepolyunsaturated fatty acids to epoxides) metabolize linoleic acid to 9S,10R-epoxy-12(Z)-octadecenoic acid and 9R,10S-epoxy-12(Z)-octadecenoic acid, i.e. the (+) and (-) epoxyoptical isomers of coronaric acid.[4][5][6] When studied in this context, the optical isomer mixture is often termed leukotoxin. These same CYP epoxygenases concurrently attack linoleic acid at the carbon 12,13 rather than 9,10double bond of linoleic acid to form a mixture of (+) and (-) epoxyoptical isomers viz., 12S,13R-epoxy-9(Z)-octadecenoic and 12R,13S-epoxy-9(Z)-octadecenoic acids. This (+) and (-) optical mixture is often termedvernolic acid when studied in plants and isoleukotoxin when studied in mammals.[4][5][6]
Coronaric acid is found in urine samples from healthy human subjects and increases 3- to 4-fold when these subjects are treated with a salt-loading diet.[5]
Coronaric andvernolic acids also form non-enzymatically when linoleic acid is exposed to oxygen and/orUV radiation as a result of the spontaneous process ofautoxidation.[7] This autoxidation complicates studies in that it is often difficult to determine if these epoxy fatty acids identified in linoleic acid-rich plant and mammalian tissues represent actual tissue contents or are artifacts formed during their isolation and detection.
In mammalian tissue, coronaric acid is metabolized to its two corresponding dihydroxystereoisomers, 9S,10R-dihydroxy-12(Z)-octadecenoic and 9R,10S-dihydroxy-12(Z)-octadecenoic acids, bysoluble epoxide hydrolase within minutes of its formation.[8] The metabolism of coronaric acid to these two products, collectively termed leukotoxin diols, appears to be critical to coronaric acid's toxicity, i.e. the diols are the toxic metabolites of the non-toxic or far less toxic coronaric acid.[8][6]
At very high concentrations, the linoleic acid-derived set of optical isomers, coronaric acid (i.e. leukotoxin) possesses toxicity similar to that of other structurally unrelated leukotoxins. It is toxic to leukocytes and other cell types, and when injected into rodents produces multiple organ failure and respiratory distress.[9][10][11][6] These effects appear to be due to its conversion to its dihydroxy counterparts, 9S,10R- and 9R,10S-dihydroxy-12(Z)-octadecenoic acids by soluble epoxide hydrolase.[8] Some studies suggest, but have not yet proven, that isoleukotoxin, acting primarily if not exclusively through its dihydroxy counterparts, is responsible for or contributes to multiple organ failure, theacute respiratory distress syndrome, and certain other cataclysmic diseases in humans (seeEpoxygenase § Linoleic acid).[10][12] Vernolic acid (i.e. isoleukotoxin) shares a similar metabolic fate in being converted by soluble epoxide hydrolase to its dihydroxide counterparts, resulting in the toxic actions of those counterparts.
At lower concentrations, isoleukotoxin and its dihydroxy counterparts can protect from the toxic actions cited above that occur at higher concentrations of isoleukotoxin and leukotoxin; they may also share with the epoxides of arachidonic acid, i.e. the epoxyeicosatreienoates (seeEpoxyeicosatrienoic acids), anti-hypertension activities.[5]
