Inhibition of membrane-bound hepatic 3 hydroxy-3 methyl glutaryl CoA reductase as the consequence of altered membrane fluidity.

The activity of hydroxy methyl glutaryl-CoA reductase in microsomes from rat and from human liver was inhibited in a non-competitive manner by fenofibric acid. High affinity of the microsomal preparation for the ligand allowed a one-step purification of the microsomal enzyme preparation, using a Sepharose gel coupled to the phenol analogue of fenofibric acid. Ther Arrhenius plots of partially purified hydroxy methyl glutaryl-CoA reductase in the microsomal fraction from rat liver showed that the break in the activation energy at 11 degrees C was abolished by the ligand. The results in the present study may be consistent with a modulation of membrane-bound HMG-CoA reductase activity.