Innis S M
Biochim Biophys Acta. 1986 Feb 12;875(2):355-61. doi: 10.1016/0005-2760(86)90186-4.
The relationship of microsomal cholesterol and phospholipid fatty acid composition to the activities of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and acyl-CoA: cholesterol acyltransferase was investigated in male, female virgin and pregnant rats when hepatic cholesterogenesis was stimulated by cholestyramine. Cholestyramine increased HMG-CoA reductase activity in both sexes but had no effect on microsomal free cholesterol level or acyl-CoA: cholesterol acyltransferase activity. The data suggest that during cholestyramine treatment high rates of bile acid synthesis are supported by preferential channelling of cholesterol into this pathway, whilst the substrate pool and activity of acyl-CoA:cholesterol acyltransferase are maintained unaltered. The lack of a consistent relationship among enzyme activities and microsomal lipid composition infers that HMG-CoA reductase and acyl-CoA:cholesterol acyltransferase are regulated in vivo by independent mechanisms which are unlikely to involve modulation by the physical properties of the microsomal lipid.
当用消胆胺刺激雄性、雌性未孕及怀孕大鼠的肝脏胆固醇生成时，研究了微粒体胆固醇和磷脂脂肪酸组成与3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶及酰基辅酶A：胆固醇酰基转移酶活性之间的关系。消胆胺增加了两性的HMG-CoA还原酶活性，但对微粒体游离胆固醇水平或酰基辅酶A：胆固醇酰基转移酶活性没有影响。数据表明，在消胆胺治疗期间，胆汁酸合成的高速率是通过胆固醇优先进入该途径来支持的，而酰基辅酶A：胆固醇酰基转移酶的底物池和活性保持不变。酶活性与微粒体脂质组成之间缺乏一致的关系，这表明HMG-CoA还原酶和酰基辅酶A：胆固醇酰基转移酶在体内受独立机制调节，这些机制不太可能涉及微粒体脂质物理性质的调节。
