Regulation of squalene epoxidase activity in rat liver.
Regulation of squalene epoxidase activity was examined in rat hepatic microsomes. The hepatic squalene epoxidase activity was high in the dark period and low in the light period. Three percent cholestyramine feeding increased the hepatic squalene epoxidase activity by 2.5-fold, and the administration of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, increased its activity by 2.1-fold. Co-administration of cholestyramine and lovastatin had a synergistic effect increasing the activity by 7.0-fold. On the other hand, cholesterol feeding reduced hepatic squalene epoxidase activity to 18%. The addition of sodium fluoride, a phosphatase inhibitor, and the treatment of the microsomes with ATP-Mg2+ had no effect on enzyme activity. HMG-CoA reductase activity has been reported to be regulated by cholesterol and unidentified metabolite(s) derived from mevalonate. However, since squalene epoxidase is less responsive than the reductase to the treatment with lovastatin, squalene epoxidase is thought to be regulated only by cholesterol pool.
Satoh
T
T
Central Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
Hidaka
Y
Y
Kamei
T
T
D000818:Animals; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000494:pharmacology; D002792:Cholestyramine Resin / Q000008:administration & dosage / Q000494:pharmacology; D004790:Enzyme Induction; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007700:Kinetics; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D010105:Oxygenases / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012969:Sodium Fluoride / Q000494:pharmacology; D050603:Squalene Monooxygenase
D002791:Cholesterol, Dietary; D002792:Cholestyramine Resin; D012969:Sodium Fluoride; D002784:Cholesterol; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D010105:Oxygenases; D050603:Squalene Monooxygenase