Cyclohexanedione herbicides are inhibitors of rat heart acetyl-CoA carboxylase

Bioorg Med Chem Lett. 2003 Oct 6;13(19):3237-42. doi: 10.1016/s0960-894x(03)00664-4.

Abstract

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.

MeSH terms

  • Acetyl-CoA Carboxylase / antagonists & inhibitors*
  • Acetyl-CoA Carboxylase / metabolism
  • Animals
  • Cyclohexanes / chemistry
  • Cyclohexanes / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Herbicides / chemistry
  • Herbicides / pharmacology*
  • Myocardium / enzymology*
  • Rats

Substances

  • Cyclohexanes
  • Enzyme Inhibitors
  • Herbicides
  • Acetyl-CoA Carboxylase