Acyl-coenzyme A: cholesterol O-acyltransferase (ACATase; EC 2.3.1.26) is a membrane-bound microsomal enzyme that catalyzes the formation of long-chain fatty-acyl cholesterol esters in rat liver and other tissues. This enzyme is important in regulating the concentration of unesterified cholesterol in the cell. Having recently demonstrated that rat liver 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase; EC 1.1.1.34), the major regulatory enzyme in cholesterol biosynthesis, undergoes in vivo phosphorylation and inactivation after a single cholesterol meal, we decided to test the hypothesis that the enzyme ACATase, important in cholesterol utilization and storage, is also subject to regulation by phosphorylation/dephosphorylation. The results show that rat liver ACATase can be reversibly inactivated/activated, in vitro, by incubation conditions that favor dephosphorylation/phosphorylation. Activation was also achieved by using a partially purified protein kinase extracted from microsomes. It is significant that HMG-CoA reductase is inactivated by phosphorylation whereas ACATase is activated by phosphorylation. ACATase is, therefore, regulated by phosphorylation in a manner exactly opposite to that of HMG-CoA reductase. We propose that the coordinate regulation of ACATase and HMG-CoA reductase by phosphorylation/dephosphorylation provides a mechanism for short-term intracellular cholesterol homeostasis.Acyl-coenzyme A:cholesterol 0-acyltransferase (ACATase) is a membrane bound microsomal enzyme that catalyzes the formation of long-chain fatty-acyl cholesterol esters in rat liver and in other tissues. It has been proposed that esterification is a mechanism for the removal of a potentially harmful excess of unesterified cholesterol by conversion to a form that can be stored intracellularly without deleterious effects to the cell (1, 2).Alternatively, at least for liver, esterified cholesterol may be utilized in the formation of lipoproteins, which are secreted from the liver and pass into the circulation (3-5). The total amount of cholesterol in the hepatic cell changes in response to changes in dietary cholesterol content and to other manipulations that affect the rate of endogenous cholesterol biosynthesis. However, the concentration of unesterified cholesterol present in the liver remains within a relatively narrow range, whereas the amount of esterified cholesterol can be remarkably increased (6)(7)(8). This effect is also clearly seen in hepatocytes from rats that have been fed fat and cholesterol (5), as well as in hepatocytes exposed to high concentrations of the sterol precursor mevalonic acid (9, 10).The activity of microsomal ACATase has been found to be greater when the amount of total cholesterol in the cell is increased (8,11). Thus ACATase appears to be important in regulating the amount of unesterified cholesterol in the cell. Previously, we have demonstrated the in vivo relevance of the phosphorylation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) as a...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.