Regulation of Short-Term Changes in Hepatic β-Hydroxy-β-methylglutaryl-CoA Reductase Activity

Abstract

Immunotitrations of rat liver hydroxymethylglutaryl-CoA (HMG-CoA) reductase activity were performed before and after short-term changes in the nutritional or hormonal state of the animals. Changes in enzyme activity (increase or decrease) within 1 h following cholesterol feeding or glucagon or mevalonolactone administration to normal rats, or insulin administration to diabetic rats were accompanied by no change in the specific activity of the enzyme, as determined from the quantity of enzyme activity inactivated by a fixed quantity of antibody. The loss in enzyme activity may have been due to conversion of the enzyme to immunounreactive products. In agreement with this conclusion, the enzyme activity lost after these short-term physiological changes was not restorable by phosphoprotein phosphatase action. On the other hand, incubation of rat liver microsomes with ATP and Mg2+ decreased the specific activity of HMGt-CoA reductase .apprx. 10-fold, as determined by immunotitration. The low specific activity produced under these conditions was increased by phosphatase action to nearly the original level. The changes in HMG-CoA reductase activity that resulted from short-term physiological changes in hormonal or nutritional states of an animal were probably brought about by a change in the quantity of enzyme and not by reversible phosphorylation of preexisting enzyme.