Characteristics of magnesium-adenosine triphosphate-dependent inactivators of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

The inhibition of homogeneous 3-hydroxy-3-methyl-glutaryl coenzyme A reductase by MgATP-dependent inactivators isolated from rat liver cytosol and microsomes was examined. The inhibition was independent of incubation time. The inhibition was readily reversed by dilution or dialysis, by the addition of EDTA, and by incubating the inhibited enzyme with glycerol and glycerol kinase to convert the ATP to ADP. The inactivated enzyme was not reactivated by various phosphatases. When inactivated in the presence of [gamma-32P]ATP, no radioactivity was incorporated into the reductase. These observations indicate that the inactivators do not exert their effects through covalent modification of the reductase.