Stereospecific induction of rat liver bilirubin UDPglucuronosyltransferase and lauric acid 12-hydroxylation by the isomers of 2-phenylpropionic acid.
The inductive effects of racemic 2-phenylpropionic acid and its isomers on rat liver bilirubin UDP-glucuronosyltransferase activity and lauric acid 12-hydroxylation (cytochrome P-452-dependent) were compared. The (S)-(+)-enantiomer and the racemic mixture gave the greatest induction of both enzyme activities, whereas (R)-(-)-2-phenylpropionic acid produced increases of only one-third of those of its antipode. The determination of the enantiomeric composition of the excreted 2-phenylpropionic acid after a single oral dose indicated that the (R)-(-)-enantiomer given as such or in the racemate was inverted to its antipode, which strongly suggests that (S)-(+)-2-phenylpropionic acid is responsible for the inductive effects observed. The demonstration of the same stereospecificity for the induction of bilirubin UDPglucuronosyltransferase and lauric acid 12-hydroxylation further indicates a close mechanistic link between these two processes.
D000818:Animals; D001663:Bilirubin / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D003580:Cytochromes / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006900:Hydroxylation; D007536:Isomerism; D007850:Lauric Acids / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010666:Phenylpropionates / Q000494:pharmacology*; D051381:Rats
D003580:Cytochromes; D007850:Lauric Acids; D010666:Phenylpropionates; C030358:lauric acid; C046362:cytochrome P-452; C013025:hydratropic acid; D014453:Glucuronosyltransferase; D001663:Bilirubin