(-)-R-fenoprofen: formation of fenoprofenyl-coenzyme A by rat liver microsomes.
The thioesterification of fenoprofen (FPF) by rat liver microsomes has been studied using an HPLC method enabling direct quantification of the FPF-CoA produced. Over the concentration range studied (5-400 microM), studies showed the participation of a single CoA ligase in the formation of FPF-CoA, in contrast with the involvement of several isozymes with different affinities, that has been found with ibuprofen (IPF). The Km for the reaction was dependent upon the presence of non-ionic detergent, a concentration of 0.05% Triton X-100 reducing the Km from 397 to 20 microM although the detergent had no effect on Vmax. The microsomal long-chain fatty acid CoA ligase was markedly enantioselective towards (-)-R-FPF and the formation of (-)-R-FP-CoA was inhibited by both the (+)-S enantiomer and palmitic acid.
Benoit
E
E
Unité associée de Toxicologie Métabolique et d'écotoxicologie INRA-ENVL, Ecole Nationale Vétérinaire de Lyon, Marcy l'Etoile, France.
Delatour
P
P
Olivier
L
L
Caldwell
J
J
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003065:Coenzyme A / Q000737:chemistry / Q000378:metabolism*; D004951:Esterification; D005279:Fenoprofen / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D017830:Octoxynol; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D010169:Palmitic Acids; D019308:Palmitic Acid; D017830:Octoxynol; D005279:Fenoprofen; D003065:Coenzyme A