Transcriptional regulation of intracellular cholesterol metabolism

动物细胞通过一系列20多种酶促反应将乙酰辅酶a合成胆固醇。此外，细胞以低密度脂蛋白（LDL）的形式从血浆中获取胆固醇，低密度脂蛋白通过LDL受体内化，并在溶酶体中水解为游离胆固醇。每个细胞必须平衡这些内部和外部来源，同时避免固醇短缺或过度积累。生物合成和摄取途径都通过反馈控制得到很好的调节。当细胞在LDL存在下培养时，3-羟基-3-甲基戊二酰辅酶A （HMG CoA）合成酶和HMG CoA还原酶的活性均下降90%以上，LDL受体的数量也减少。在缺乏LDL的情况下，细胞维持了这两种酶的高活性，这两种酶是生物合成途径的限速酶，并且在细胞表面也维持了大量的LDL受体。我们评估了最近在理解细胞内胆固醇代谢的转录和转录后调节机制方面的进展。

Animal cells synthesize cholesterol from acetyl CoA through a series of more than 20 enzymatic reactions. In addition, cells obtain cholesterol from plasma in the form of lowdensity lipoprotein (LDL), which is internalized via the LDL receptor and hydrolyzed to free cholesterol in lysosomes. Each cell must balance these internal and external sources while avoiding sterol shortage or over-accunrulation. Both the biosynthetic and uptake pathways are well-regulated through feedback control. When cells are cultured in the presence of LDL,the activity of both 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) synthase and HMG CoA reductase decline by more than 90% and the number of LDL receptors also decreases. In the absence of LDL,the cells maintain high activities of these two enzymes, which are rate-limiting enzymes of the biosynthetic pathway, and also maintain a large number of LDL receptors on their surface. We assess recent progress in understanding the mechanisms involved in transcriptional and posttranscriptional regulation of intracellular cholesterol metabolism.