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通过将非酯化胆固醇转移至大鼠肝微粒体囊泡对3-羟基-3-甲基戊二酰辅酶A还原酶和酰基辅酶A-胆固醇酰基转移酶的调节

Modulation of 3-hydroxy-3-methylglutaryl-CoA reductase and of acyl-CoA--cholesterol acyltransferase by the transfer of non-esterified cholesterol to rat liver microsomal vesicles.

作者信息

Mitropoulos K A, Venkatesan S, Reeves B E, Balasubramaniam S

出版信息

Biochem J. 1981 Jan 15;194(1):265-71. doi: 10.1042/bj1940265.

Abstract

The incubation of rat liver microsomal fraction with a serum preparation followed by the re-isolation of the microsomal membranes has resulted in an increase in the concentration of non-esterified cholesterol, a considerable decrease in the activity of 3-hydroxy-3-methylglutaryl-CoA reductase and in an increase in the activity of acyl-CoA-cholesterol acyltransferase in the treated microsomal preparation. These effects were related to the concentration of serum in the incubation mixture and to the duration of the incubation. The transfer of non-esterified cholesterol was specific in that the content of protein and the total phospholipids were similar in the original microsomal fraction and the serum-treated microsomal preparation. The incubation of the microsomal fraction with lipoprotein-deficient serum or with no serum resulted in both cases in small changes in the non-esterified cholesterol, the esterified cholesterol and the total phospholipid content in the treated preparations compared with these concentrations in the original microsomal fraction, whereas the activity of acyl-CoA-cholesterol acyltransferase and of 3-hydroxy-3-methylglutaryl-CoA reductase was similar in the lipoprotein-deficient-serum-treated and the buffer-treated microsomal preparations. The activity of 3-hydroxy-3-methylglutaryl-CoA reductase was lower and the activity of acyl-CoA-cholesterol acyltransferase was higher in the lipoprotein-deficient-serum-treated and the buffer-treated microsomal preparations as compared with these activities in the original microsomal fraction. However, the serum-treated microsomal preparation had considerably lower activity of 3-hydroxy-3-methylglutaryl-CoA reductase and considerably higher activity of acyl-CoA-cholesterol acyltransferase than these activities in buffer-treated and in lipoprotein-deficient-serum-treated microsomal preparations.

摘要

用血清制剂孵育大鼠肝脏微粒体部分,随后重新分离微粒体膜,结果导致处理后的微粒体制剂中游离胆固醇浓度增加,3-羟基-3-甲基戊二酰辅酶A还原酶活性显著降低,酰基辅酶A胆固醇酰基转移酶活性增加。这些效应与孵育混合物中血清的浓度以及孵育时间有关。游离胆固醇的转移具有特异性,因为原始微粒体部分和经血清处理的微粒体制剂中的蛋白质含量和总磷脂含量相似。用缺乏脂蛋白的血清或无血清孵育微粒体部分,与原始微粒体部分中的这些浓度相比,两种情况下处理后的制剂中游离胆固醇、酯化胆固醇和总磷脂含量均有微小变化,而在缺乏脂蛋白血清处理的和缓冲液处理的微粒体制剂中,酰基辅酶A胆固醇酰基转移酶和3-羟基-3-甲基戊二酰辅酶A还原酶的活性相似。与原始微粒体部分中的这些活性相比,缺乏脂蛋白血清处理的和缓冲液处理的微粒体制剂中3-羟基-3-甲基戊二酰辅酶A还原酶的活性较低,酰基辅酶A胆固醇酰基转移酶的活性较高。然而,与缓冲液处理的和缺乏脂蛋白血清处理的微粒体制剂中的这些活性相比,经血清处理的微粒体制剂中3-羟基-3-甲基戊二酰辅酶A还原酶的活性显著较低,酰基辅酶A胆固醇酰基转移酶的活性显著较高。

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