Studies on toxic oil syndrome: stereoselective hydrolysis of 3-(phenylamino)propane-1,2-diol esters by human pancreatic lipase.
The ingestion of rapeseed oil batches denatured with aniline and illegally refined and distributed by street vendors was responsible for toxic oil syndrome (TOS), an intoxication episode that took place in Spain in 1981, causing over 400 deaths and affecting more than 20,000 people. Despite the intense research efforts carried out to date, the compounds responsible for that intoxication have not been elucidated. Nevertheless, epidemiological studies have pointed to fatty acid mono- and diesters of 3-phenylamino-1,2-propanediol (PAP) as the biomarkers of those toxic oil batches. The structure of these esters bears common features with that of triglycerides, which suggested that PAP esters could follow the route of lipids metabolism up to a certain extent. The incubation of racemic PAP dioleyl ester with human pancreatic lipase (hPL) led to the formation of the corresponding stereoisomeric monoesters bearing the oleyl residue at C-2, although a kinetic resolution in favor of the (S)-enantiomer was observed. These monoesters are unstable and in equilibrium with their corresponding regioisomers with the acyl residue at C-1, apparently without the intervention of the lipase. Finally, incubations of these latter monoesters with hPL led to the formation of the respective PAP enantiomers. Again, the kinetic resolution of this hydrolytic process favored the formation of the enantiomer with the (S)-configuration. Taken together, these results showed that PAP esters are substrates of hPL and that the two hydrolytic steps exhibit kinetic resolution in favor of the (S)-enantiomers.
Morató
Anna
A
Department of Biological Organic Chemistry, Institut d'Investigacions Químiques i Ambientals de Barcelona (CSIC), 08034 Barcelona, Spain.
Martínez-Cabot
Anna
A
Escabrós
Jordi
J
Bujons
Jordi
J
Messeguer
Angel
A
D029741:Brassica rapa / Q000737:chemistry*; D005229:Fatty Acids, Monounsaturated; D006801:Humans; D006868:Hydrolysis; D008049:Lipase / Q000378:metabolism*; D010179:Pancreas / Q000201:enzymology; D010938:Plant Oils / Q000737:chemistry* / Q000506:poisoning*; D011041:Poisoning / Q000209:etiology / Q000378:metabolism; D011409:Propylene Glycols / Q000378:metabolism*; D000074262:Rapeseed Oil; D013237:Stereoisomerism; D013577:Syndrome
D005229:Fatty Acids, Monounsaturated; D010938:Plant Oils; D011409:Propylene Glycols; D000074262:Rapeseed Oil; C092835:3-(N-phenylamino)-1,2-propanediol 1,2-dioleoyl ester; D008049:Lipase