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.
D000818:Animals; D002846:Chromatography, Affinity; D011345:Fenofibrate / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000302:isolation & purification; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D066298:In Vitro Techniques; D008560:Membrane Fluidity; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C006012:fenofibric acid; D006903:Hydroxymethylglutaryl CoA Reductases; D011345:Fenofibrate