Evidence for phosphorylation/dephosphorylation of rat liver acyl-CoA:cholesterol acyltransferase.
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.
D000217:Acyltransferases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004789:Enzyme Activation; D008099:Liver / Q000201:enzymology*; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D002785:Sterol O-Acyltransferase / Q000378:metabolism*
D000255:Adenosine Triphosphate; D000217:Acyltransferases; D002785:Sterol O-Acyltransferase; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D008274:Magnesium