UNSATURATED FATTY ACYL-COA INHIBITION OF CHOLESTEROL-SYNTHESIS INVITRO
UNSATURATED FATTY ACYL-COA INHIBITION OF CHOLESTEROL-SYNTHESIS INVITRO
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DOI：
10.1016/0005-2760(77)90004-2
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发表时间：
1977-01-01
期刊：
影响因子：
--
通讯作者：
WYNN, JO
中科院分区：
文献类型：
--
作者：
FAAS, FH;CARTER, WJ;WYNN, JO
在大鼠肝脏线粒体后上清系统中研究了饱和脂肪酸和不饱和脂肪酸及脂肪酸酰基辅酶A硫酯对体外胆固醇合成的影响。100亩游离脂肪酸。M不影响体外胆固醇合成。10-100亩各种脂肪酰基辅酶a硫酯。M抑制[14C]乙酸掺入洋地黄苷沉淀的甾醇，对越不饱和的衍生物造成的抑制作用最大。花生四烯酰基辅酶a在10亩。M对[14C]醋酸酯掺入甾醇的抑制率为17%和50 .mu。M抑制55%。[14C]乙酰辅酶a掺入血清同样受到抑制，但[14C]甲羟戊酸掺入不受抑制。因此，抑制作用可能是在胆固醇合成的速率控制步骤，即- β -羟基- β -的转化。-甲基戊二酰辅酶a到甲羟戊酸。不饱和脂肪酸酰基辅酶a硫酯可能在调节胆固醇合成中起重要作用。研究是为了确定先前观察到的体外甲状腺素对胆固醇合成的抑制是否与甲状腺素刺激脂肪酸去饱和有关。甲状腺素50。M使[14C]醋酸优先掺入不饱和脂肪酸，同时抑制醋酸掺入固醇。然而，不饱和脂肪酰基辅酶a硫酯的充分增加不足以解释甲状腺素对胆固醇合成的抑制作用。
The influence of saturated and unsaturated fatty acids and fatty acyl coenzyme A thioesters on cholesterol synthesis in vitro was studied in a rat liver post-mitochondrial supernatant system. Free fatty acids at 100 .mu.M do not influence in vitro cholesterol synthesis. Various fatty acyl-CoA thioesters at 10-100 .mu.M inhibit [14C]acetate incorporation into digitonin-precipitable sterols, the more unsaturated derivatives causing the greatest inhibition. Arachidonoyl-CoA at 10 .mu.M inhibits [14C]acetate incorporation into sterols 17% and 50 .mu.M inhibits 55%. [14C]Acetyl-CoA incorporation into serols is similarly inhibited but [14C]mevalonate incorporation is not inhibited. Thus, the inhibition may be on the rate-controlling step of cholesterol synthesis, the conversion of .beta.-hydroxy-.beta.-methylglutaryl-CoA to mevalonate. Unsaturated fatty acyl-CoA thioesters may be important in regulating cholesterol synthesis. Studies were undertaken to determine if the previously observed inhibition of cholesterol synthesis by thyroxine in vitro may relate to the thyroxine stimulation of fatty acid desaturation. Thyroxine at 50 .mu.M causes a preferential incorporation of [14C]acetate into unsaturated fatty acids while inhibiting acetate incorporation into sterols. However, a sufficient increase in unsaturated fatty acyl-CoA thioesters to account for the thyroxine inhibition of cholesterol synthesis was not demonstrated.