Scallen T J, Sanghvi A
Proc Natl Acad Sci U S A. 1983 May;80(9):2477-80. doi: 10.1073/pnas.80.9.2477.
Our laboratories have investigated the role of phosphorylation/dephosphorylation in the regulation of three key enzymes in cholesterol metabolism. 3-Hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase (EC 1.1.1.34), the major regulatory enzyme in cholesterol biosynthesis, is inhibited by phosphorylation. Acyl-CoA:cholesterol O-acyltransferase (ACATase; EC 2.3.1.26) and cholesterol 7 alpha-hydroxylase (EC 1.14.13.7), key regulatory enzymes in the utilization of cholesterol, are activated by phosphorylation. In view of these results, we propose that short-term regulation of the concentration of intracellular unesterified cholesterol is achieved by a coordinate phosphorylation/dephosphorylation of these three enzymes. For example, if cholesterol enters the liver cell, HMG-CoA reductase would be inhibited by phosphorylation and biosynthesis of cholesterol would be reduced; however, reactions utilizing cholesterol would be activated, due to the phosphorylation of ACATase and cholesterol 7 alpha-hydroxylase. Thus, the phosphorylation/dephosphorylation of these three enzymes provides an elegant short-term mechanism for the homeostasis of intracellular unesterified cholesterol.
我们的实验室研究了磷酸化/去磷酸化在胆固醇代谢中三种关键酶调节作用中的角色。3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶（EC 1.1.1.34）是胆固醇生物合成中的主要调节酶，其活性受磷酸化抑制。酰基辅酶A：胆固醇O-酰基转移酶（ACATase；EC 2.3.1.26）和胆固醇7α-羟化酶（EC 1.14.13.7）是胆固醇利用过程中的关键调节酶，它们的活性受磷酸化激活。鉴于这些结果，我们提出通过这三种酶的协同磷酸化/去磷酸化作用来实现细胞内未酯化胆固醇浓度的短期调节。例如，如果胆固醇进入肝细胞，HMG-CoA还原酶会因磷酸化而被抑制，胆固醇的生物合成会减少；然而，由于ACATase和胆固醇7α-羟化酶的磷酸化，利用胆固醇的反应会被激活。因此，这三种酶的磷酸化/去磷酸化作用为细胞内未酯化胆固醇的稳态提供了一种精妙的短期调节机制。
