Dissociation of increased lauric acid omega-hydroxylase activity from the antilipidemic action of clofibrate.
Clofibrate, an antilipidemic drug that acts by a still obscure mechanism, is known to specifically increase up to 30-fold the activity of the hepatic cytochrome P-450 isozyme that omega-hydroxlates lauric acid. The thesis that accelerated catabolism of medium-length fatty acids initiated by omega-hydroxylation contributes significantly to the antilipidemic action of clofibrate has been examined by measuring the impact on serum triglyceride levels of coadministering clofibrate and a suicide substrate that inactivates the hydroxylase. The results suggest that the antilipidemic action of clofibrate does not depend critically on the enhanced omega-hydroxylation of fatty acids.
D000818:Animals; D002994:Clofibrate / Q000494:pharmacology*; D042926:Cytochrome P-450 CYP4A; D005227:Fatty Acids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006900:Hydroxylation; D008099:Liver / Q000201:enzymology; D008297:Male; D006899:Mixed Function Oxygenases / Q000032:analysis* / Q000037:antagonists & inhibitors; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014230:Triazoles / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D014230:Triazoles; D014280:Triglycerides; C033020:1-aminobenzotriazole; C040948:11-dodecynoic acid; C048289:10-undecynoic acid; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A; D002994:Clofibrate