Inhibition of palmitoyl CoA deacylase by chlorophenoxyisobutyrate and betabenzalbutyrate.

Palmitoyl CoA deacylase activity was measured in preparations of rat liver microsomes. Two hypolipidemic agents, chlorophenoxyisobutyrate and betabenzalbutyrate caused inhibition of palmitoyl CoA deacylase in vitro. The I(50) values for chlorophenoxyisobutyrate and betabenzalbutyrate were 5.0 and 7.5 mm, respectively. The inhibition by both agents was reversible, and both drugs lowered the palmitoyl CoA-binding capacity of microsomes. The deacylase reaction rate was maximum when the binding of palmitoyl CoA to soluble or microsomal protein was low. Addition of albumin to the reaction mixture resulted in greater binding of palmitoyl CoA to protein and a lower reaction rate. Inhibition of the deacylase by chlorophenoxyisobutyrate and betabenzalbutyrate also was greater when palmitoyl CoA was not protein bound. The inhibition of palmitoyl CoA deacylase by these hypolipidemic agents may contribute to their effects on lipid metabolism.