Satoh T, Hidaka Y, Kamei T
Central Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
J Lipid Res. 1990 Nov;31(11):2095-101.
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.
在大鼠肝微粒体中检测了角鲨烯环氧酶活性的调节情况。肝角鲨烯环氧酶活性在黑暗期较高，在光照期较低。给予3%的消胆胺可使肝角鲨烯环氧酶活性提高2.5倍，给予3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂洛伐他汀可使其活性提高2.1倍。同时给予消胆胺和洛伐他汀具有协同作用，可使活性提高7.0倍。另一方面，给予胆固醇可使肝角鲨烯环氧酶活性降至18%。添加磷酸酶抑制剂氟化钠以及用ATP-Mg2+处理微粒体对酶活性均无影响。据报道，HMG-CoA还原酶活性受胆固醇和由甲羟戊酸衍生的未知代谢物调节。然而，由于角鲨烯环氧酶对洛伐他汀处理的反应不如还原酶灵敏，因此认为角鲨烯环氧酶仅受胆固醇池调节。
