3-Hydroxy-3-methylglutaryl Coenzyme A Reductase

Abstract

Abstract 3-Hydroxy-3-methylglutaryl coenzyme A reductase, the rate-controlling enzyme of cholesterol biosynthesis in rat liver, has been solubilized and purified 130-fold from rat liver microsomes. Evidence is presented to suggest that the enzyme is localized to the surface of the microsomal membrane. 3-Hydroxy-3-methylglutaryl-CoA reductase can be removed from microsomes by mild treatments such as exposure to high salt or glycerol concentrations which leave the bi-laminar structure of the microsomal membrane intact. The solubilized enzyme is rapidly inactivated by chilling to 4° and is protected from this cold-induced inactivation by salt only at concentrations in the range of 4 m. 3-Hydroxy-3-methylglutaryl-CoA reductase is the first solubilized microsomal enzyme reported to be cold-sensitive.