Properties of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase Solubilized from Rat Liver and Hepatoma

In hepatomas, the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-controlling enzyme in cholesterol biosynthesis, is not normally suppressed by cholesterol. To examine the biochemical mechanism of this loss of feedback control of cholesterol synthesis, a comparison was made of the properties of 3-hydroxy-3-methylglutaryl coenzyme A reductase after solubilization and partial purification from microsomes of normal rat liver and of a minimal deviation rat hepatoma. The solubilized enzyme from the two sources behaved identically with respect to substrate kinetics, heat inactivation, cold inactivation, and gel filtration. By the use of a new method that permits assay of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity after polyacrylamide gel electrophoresis, it was shown that the solubilized hepatoma enzyme and the normal liver enzyme had similar electrophoretic mobility. It is concluded that the failure of hepatomas to suppress 3-hydroxy-3-methyl-glutaryl coenzyme A reductase activity is not due to the production of an altered form of the enzyme.