Results ofin vivometabolism studies with acrylic acid (AA) have indicated that 60–80of the administered dose is excreted as CO2within 2–8 hr of oral dosing of rats; however, the pathway of AA metabolism to CO2in mammals has not been determined. To define this route, rat hepatocytes were isolated and incubated with 1–14CAA in a sealed vial modified to trap evolved14CO2Rapid oxidation of AA to CO2was observed. Similar incubations conducted with rat liver homogenates fortified with ATP, ADP, coenzyme A, carnitine, and malate also resulted in oxidation of AA. Mitochondria isolated from liver homogenates were incubated with AA under the same conditions and yielded higher rates of AA oxidation than homogenates. Addition of equimolar amounts of propionic acid, 3-hydroxypropionic acid, or 3-mer-captopropionic acid significantly inhibited the oxidation of AA by mitochondria. HPLC analysis of the mitochondrial incubation mixtures indicated that a single major metabolite, which coeluted with 3-hydroxypropionate, accumulated in the solution. The results indicate that AA is rapidly incorporated into a mitochondrial pathway for propionic acid catabolism that results in the release of CO2and possible bioincorporation as acetate. This pathway appears to be the principal route of detoxification of AA in ma
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