Coronaric acid

Coronaric acid is found in the seed oils derived from plants in the sunflower family, such as Helianthus annuus and Xeranthemum annuum. Coronaric acid is also formed by the cells and tissues of various mammalian (including human) species through the metabolism of linoleic acid by cytochrome P450 (CYP) epoxygenase enzymes. These CYPs (CYP2C9 and probably other CYPs that metabolize polyunsaturated 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 (-) epoxy optical isomers of coronaric acid. 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 9,10 double bond of linoleic acid to form a mixture of (+) and (-) epoxy optical isomers viz., 12S,13R-epoxy-9(Z)-octadecenoic and 12R,13S-epoxy-9(Z)-octadecenoic acids. This (+) and (-) optical mixture is often termed vernolic acid when studied in plants and isoleukotoxin when studied in mammals. 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 two corresponding dihydroxy stereoisomers, 9S,10R-dihydroxy-12(Z)-octadecenoic and 9R,10S-dihydroxy-12(Z)-octadecenoic acids, by soluble epoxide hydrolase within minutes of its formation. 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. ==Activities==

Toxicities 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. 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. 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. ==References==