Cyclohexanedione herbicides are inhibitors of rat heart acetyl-CoA carboxylase.
Acetyl CoA carboxylase (ACC) catalyzes the carboxylation of acetyl CoA to form malonyl CoA. In skeletal muscle and heart, malonyl CoA functions to regulate lipid oxidation by inhibition of carnitine palmitoyltransferase-1, an enzyme which controls the entry of long chain fatty acids into mitochondria. We have found that several members of the cyclohexanedione class of herbicides are competitive inhibitors of rat heart ACC. These compounds constitute valuable reagents for drug development and the study of ACCbeta, a validated anti-obesity target.
Seng
Thomas W
TW
Endocrine Research, Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Drop Code 0304, Indianapolis, IN 46285, USA.
Skillman
Tiffanie R
TR
Yang
Nengyu
N
Hammond
Craig
C
D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D003510:Cyclohexanes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006540:Herbicides / Q000737:chemistry / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology*; D051381:Rats
D003510:Cyclohexanes; D004791:Enzyme Inhibitors; D006540:Herbicides; D000103:Acetyl-CoA Carboxylase