Coronaric acid

Coronaric acid

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
Identifiers
Jmol interactive 3D	Image
PubChem	6246154
InChI InChI=1S/C18H32O3/c1-2-3-4-5-7-10-13-16-17(21-16)14-11-8-6-9-12-15-18(19)20/h7,10,16-17H,2-6,8-9,11-15H2,1H3,(H,19,20)/b10-7- Key: FBUKMFOXMZRGRB-YFHOEESVSA-N
SMILES CCCCC/C=C\CC1C(O1)CCCCCCCC(=O)O
Properties
Chemical formula	C18H32O3
Molar mass	296.45 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Coronaric acid is a mono-unsaturated, epoxide derivative of the di-saturated fatty acid, linoleic acid (i.e. 9(Z),12(Z) octadecadienoic acid. It is a mixture of the two optically active isomers of 12(Z) 9,10-epoxy-octadecenoic acid. This mixture isalso termed 9,10-epoxy-12Z-octadecenoic acid or 9(10)-EpOME^[1] and when formed by or studied in mammalians, isoleukotoxin.

Occurrence

Coronaric acid is found in the seed oils derived from plants in sunflower family such as (Helianthus annuus)^[2] and Xeranthemum annuum.^[3]

Coronaric acid is also formed by the cells and tissues of various mammalian species through the metabolism of linoleic acid by cytochrome P450 (CYP) epoxygenase enzymes. These CYPs (CYP2C9 is known and many of the other CYPs that metabolize other polyunsaturated fatty acids to their corresponding epoxides (see epoxygenase) are thought to) metabolize linoleic acid to (+) 12S,13R-epoxy-9(Z)-octadecaenoic acid and (-) 12R,13S-epoxy-9(Z)-octadecaenoic acid, i.e. the (+) and (-) epoxy optical isomers of coronaric acid.^[4][5][6] When studied in this context, the optical isomer mixture is often termed isoleukotoxin. This same CYP epoxygenases concurrently attack linoleic acid at the carbon 9,10 rather than 12,13 double bond of linoleic acid to form a mixture of (+) and (-) epoxy optical isomers viz., 9S,10R-epoxy-12(Z)-octadecaenoic and 9R,10S-epoxy-12(Z)-octadecaenoic acids. This (+) and (-) optical mixture is often termed vernolic acid when studied in plants and leukotoxin when studied in mammals.^[7][8][9]

Coronoric 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.^[10]

Coronaric and vernolic acids also form non-enzymatically when linoleic acid is exposed to oxygen and/or UV radiation as a result of the spontaneous process of autooxidation.^[11] 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.

Metabolism

In mammalian tissue, coronaric acid is metabolized to its corresponding dihydroxy stereoisomers, 12S,13R-dihydroxy-9(Z)-octadecaenoic acid and 12R,13S-dihydroxy-9(Z)-octadecaenoic acid by soluble epoxide hydrolase within minutes of its formation.^[12] This metabolism may be critical to its relevance as a toxic agent.

Activities

Toxicities

At very high concentrations, the linoleic acid-derived set of optical isomers, coronaric acid (i.e. isoleukotoxin), possesses activities similar to that of other structurally unrelated leukotoxins viz., It is toxic to leukocytes and other cell types and when injected into rodents produce multiple organ failure and respiratory distress.^{[13][14][15][16]} These effects appear due to its onversion to its dihydroxy counterparts, 9S,10R- and 9R,10S-dihydroxy-12(Z)-octadecaenoic acids by soluble epoxide hydrolase.^[17] Some studies suggest but have not yet proven that isoleukotoxin, acting primarily if not exclusively through its dihydroxy counterparts, is responsible for or contribute to multiple organ failure, the acute respiratory distress syndrome, and certain other cataclysmic diseases in humans (see epoxygenase section on linoleic acid).^[18][19][20] Vernolic acid (i.e. leukotoxin) shares a similar metabolic fate in being converted by soluble epoxide hydrolase to its dihydroxide counterparts and toxic actions of these hydroxide counterparts.

Other activities

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 (see Epoxyeicosatrienoic acids), anti-hypertension activities.^[21]

References