Transcriptional regulation of intracellular cholesterol metabolism

动物细胞通过20多个酶反应从乙酰辅酶A合成胆固醇。此外，细胞从血浆中以低密度脂蛋白(LDL)的形式获得胆固醇，低密度脂蛋白通过低密度脂蛋白受体内化，并在溶酶体中水解为游离胆固醇。每个细胞都必须平衡这些内部和外部来源，同时避免类固醇短缺或过度积累。通过反馈控制，生物合成和吸收途径都得到了很好的调节。当细胞与低密度脂蛋白共同培养时，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，低密度脂蛋白受体数目也减少。在没有低密度脂蛋白的情况下，细胞维持这两种酶的高活性，这两种酶是生物合成途径的限速酶，并保持其表面大量的低密度脂蛋白受体。我们评估了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最新进展。

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.