title: Rate and route of oxidation of acrylic acid to carbon dioxide in rat liver.
abstract: Results of in vivo metabolism studies with acrylic acid (AA) have indicated that 60-80% of the administered dose is excreted as CO2 within 2-8 hr of oral dosing of rats; however, the pathway of AA metabolism to CO2 in mammals has not been determined. To define this route, rat hepatocytes were isolated and incubated with [1-14C]AA in a sealed vial modified to trap evolved 14CO2. Rapid oxidation of AA to CO2 was 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-mercaptopropionic 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 CO2 and possible bioincorporation as acetate. This pathway appears to be the principal route of detoxification of AA in mammals.
authors.affiliation: Rohm and Haas Company, Toxicology Department, Spring House, Pennsylvania 19477.
authors.forename: L
authors.initials: L
authors.lastname: Finch
authors.forename: C B
authors.initials: CB
authors.lastname: Frederick
mesh_terms: D000179:Acrylates / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D008099:Liver / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D011422:Propionates / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000179:Acrylates; D011422:Propionates; D002245:Carbon Dioxide; C036658:acrylic acid; C029658:propionic acid