Differential inhibition of long-chain acyl-CoA hydrolases by hypolipidemic drugs in vitro

Biochem Pharmacol. 1992 Feb 4;43(3):639-44. doi: 10.1016/0006-2952(92)90589-b.


The effect of in vitro addition of three hypolipidemic drugs (clofibric acid, bezafibrate and gemfibrozil) on rat palmitoyl-CoA hydrolases has been studied, by using a spectrophotometric method (Berge RK, Biochim Biophys Acta 574: 321-333, 1979) optimized for valoration of crude enzyme preparations. Mitochondrial and microsomal hepatic palmitoyl-CoA hydrolase activities were inhibited by the three drugs in a concentration-dependent fashion. The order of inhibitory potency was gemfibrozil greater than bezafibrate greater than clofibric acid, irrespective of the enzyme activity tested. Cytosolic rat brain palmitoyl-CoA hydrolase activity was not affected. Kinetic studies with gemfibrozil on the solubilized microsomal palmitoyl-CoA hydrolase activity point to a mixed non-competitive type of inhibition.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bezafibrate / pharmacology
  • Clofibric Acid / pharmacology
  • Gemfibrozil / pharmacology
  • Hypolipidemic Agents / pharmacology*
  • Liver / drug effects
  • Liver / enzymology*
  • Male
  • Palmitoyl Coenzyme A / pharmacology
  • Palmitoyl-CoA Hydrolase / antagonists & inhibitors*
  • Rats
  • Rats, Inbred Strains
  • Subcellular Fractions / enzymology


  • Hypolipidemic Agents
  • Palmitoyl Coenzyme A
  • Clofibric Acid
  • Palmitoyl-CoA Hydrolase
  • Gemfibrozil
  • Bezafibrate