INHIBITION OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE-ACTIVITY IN MORRIS HEPATOMA-7800 AFTER INTRAVENOUS-INJECTION OF MEVALONIC ACID

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (12) , 4717-4721
Abstract
The effect of i.v. injection of mevalonate on the activity of microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase was studied in livers from non-tumor-bearing rats and in host liver and hepatomas from rats bearing transplantable Morris hepatoma 7800. A single bolus injection of 100 mg of mevalonate in non-tumor-bearing male rats caused a 90% inhibition of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity within 2 h. Mevalonate injection caused a 50-60% reduction in enzyme activity of hepatomas but no significant decline in the enzyme activity in host livers. Thirty minutes after injection of [14C]mevalonate in a similarly sized bolus, the ratio of specific activities of cholesterol in liver:hepatoma:kidney:blood was 13:5.6:0.5:1. The liver and hepatoma efficiently used mevalonate for the synthesis of cholesterol. The inhibition of enzyme activity in the liver of non-tumor-bearing rats and in the transplantable hepatomas may have resulted from the accumulation of endogenous cholesterol in microsomal membranes. The activity of cholesterol 7.alpha.-hydroxylase, the rate-controlling enzyme for bile acid synthesis, in the hepatoma generally did not differ from that in the host or control livers.