Differential inhibition of long-chain acyl-CoA hydrolases by hypolipidemic drugs in vitro.
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.
Departamento de Farmacología y Química Terapéutica, Facultad de Farmacia, Universidad de Barcelona, Spain.
R M
RM
Sánchez
M
M
Alegret
T
T
Adzet
M
M
Merlos
J C
JC
Laguna
D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology; D002995:Clofibric Acid / Q000494:pharmacology; D015248:Gemfibrozil / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology; D010170:Palmitoyl-CoA Hydrolase / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000201:enzymology
D000960:Hypolipidemic Agents; D010171:Palmitoyl Coenzyme A; D002995:Clofibric Acid; D010170:Palmitoyl-CoA Hydrolase; D015248:Gemfibrozil; D001629:Bezafibrate