REGULATION OF CHOLESTEROL BIOSYNTHESIS IN RAT LIVER - DIURNAL CHANGES OF ACTIVITY AND INFLUENCE OF BILE ACIDS
REGULATION OF CHOLESTEROL BIOSYNTHESIS IN RAT LIVER - DIURNAL CHANGES OF ACTIVITY AND INFLUENCE OF BILE ACIDS
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DOI：
10.1016/0003-9861(69)90482-2
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发表时间：
1969-01-01
影响因子：
3.9
通讯作者：
LYNEN, F
中科院分区：
文献类型：
--
作者：
BACK, P;HAMPRECHT, B;LYNEN, F
维持在半合成饮食的大鼠显示出较低的醋酸盐掺入胆固醇的速率，与喂食商业饮食的大鼠相比。在半合成饲料中添加胆汁酸螯合阴离子交换树脂可使肝脏胆固醇合成活性增加数倍，通过大鼠肝切片和肝提取物证实了乙酸-1-14 C（而不是甲羟戊酸）掺入胆固醇的昼夜节律。午夜的合成比白天可测量的合成增加了3.8倍。这种节律性的活性变化是由于合成甲羟戊酸的酶系统的活性变化所致。这些活性的节律性变化被认为是由于酶蛋白水平的改变。当与饮食一起给予时，胆酸也在该酶步骤中作为胆固醇生物合成的抑制剂起作用，并且显示出比饮食胆固醇有效得多，但是肝脏中胆酸的浓度水平没有显示出与正常进食条件下观察到的节律性活动变化相关的改变。
Rats maintained on semisynthetic diets show a low rate of acetate incorporation into cholesterol, when compared with rats fed a commercial diet. Addition of a bile acid sequestering anion exchange resin to the semisynthetic diet causes a several-fold increase of hepatic cholesterol synthetic activity.A diurnal rhythm is demonstrated for the incorporation of acetate-1-14C (but not of mevalonate) into cholesterol by rat liver slices and liver extracts. Synthesis at midnight is increased by a factor of 3.8 over the synthesis which is measurable during the day. The rhythmic activity changes are due to activity changes of the enzyme system synthesizing mevalonate. These rhythmic changes of activity are assumed to be due to alterations of the level of enzyme protein. Cholic acid, when given with the diet, also acts at this enzymic step as inhibitor of cholesterol biosynthesis and is shown to be much more effective than dietary cholesterol, but the concentration levels of cholic acid in liver do not show alterations which can be correlated with the observed rhythmic activity changes under conditions of normal feeding.