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脂蛋白对人成纤维细胞中3-羟基-3-甲基戊二酰辅酶A还原酶活性的调节

Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts by lipoproteins.

作者信息

Brown M S, Dana S E, Goldstein J L

出版信息

Proc Natl Acad Sci U S A. 1973 Jul;70(7):2162-6. doi: 10.1073/pnas.70.7.2162.

Abstract

The activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34), the rate-limiting enzyme of hepatic cholesterol biosynthesis, is suppressed in human fibroblasts cultured in the presence of serum. This enzyme activity increases by more than 10-fold after the removal of serum from the medium. The rise in enzyme activity requires de novo protein synthesis and is not accompanied by changes in the activities of several other cellular enzymes. The factor responsible for the suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured fibroblasts is present in the sera of at least four mammalian species, and in human serum it is found in the low-density lipoproteins. Human high-density lipoproteins, very low-density lipoproteins from chicken egg yolk, and the fraction of human serum containing no lipoproteins do not suppress the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

摘要

3-羟基-3-甲基戊二酰辅酶A还原酶(EC 1.1.1.34)是肝脏胆固醇生物合成的限速酶,在有血清存在的情况下培养的人成纤维细胞中,其活性受到抑制。从培养基中去除血清后,该酶活性增加超过10倍。酶活性的升高需要从头合成蛋白质,并且不伴随其他几种细胞酶活性的变化。在至少四种哺乳动物的血清中存在负责抑制培养的成纤维细胞中3-羟基-3-甲基戊二酰辅酶A还原酶活性的因子,在人血清中,它存在于低密度脂蛋白中。人高密度脂蛋白、来自鸡卵黄的极低密度脂蛋白以及不含脂蛋白的人血清部分均不抑制3-羟基-3-甲基戊二酰辅酶A还原酶的活性。

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